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RESEARCH PRO00015001 TAK-659	

Types:      Research Oncology Treatment
Synonyms:  TAK, TAK659, TAK-659, 15001

Screening / Baseline	Repeat 1 time	Cycle length: 28 days	Day -28 to Day -1	Perform every 1 day x1		Labs
☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		☑	MAGNESIUM LEVEL	Interval: --	Occurrences: --		☑	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		☑	URIC ACID LEVEL	Interval: --	Occurrences: --		☑	LDH	Interval: --	Occurrences: --		☑	GGT	Interval: --	Occurrences: --		☑	AMYLASE LEVEL	Interval: --	Occurrences: --		☑	LIPASE LEVEL	Interval: --	Occurrences: --		☑	CREATINE KINASE, TOTAL (CPK)	Interval: --	Occurrences: --		☑	LACTATE DEHYDROGENASE (LD) ISOENZYMES	Interval: --	Occurrences: --		☑	EPSTEIN-BARR VIRUS ANTIBODY PANEL	Interval: --	Occurrences: --		☑	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	If applicable
		☑	CD3 ENUMERATION	Interval: --	Occurrences: --		☑	CD19	Interval: --	Occurrences: --		☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		☑	MANUAL DIFFERENTIAL	Interval: --	Occurrences: --	Comments:	If needed
		☑	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --		☑	BIOPSY BONE MARROW	Interval: --	Occurrences: --			Imaging
☑	CT SOFT TISSUE NECK W CONTRAST	Interval: --	Occurrences: --	Comments:	If appropriate
		☑	CT CHEST W CONTRAST ABDOMEN W CONTRAST PELVIS W CONTRAST	Interval: --	Occurrences: --		☑	PET CT SKULL BASE TO MID THIGH	Interval: --	Occurrences: --			Nursing Orders
☑	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
		☑	ONC NURSING COMMUNICATION 6	Interval: --	Occurrences: --	Comments:	Vital signs  (blood pressure, heart rate, respiratory rate, temperature)
		☑	ONC NURSING COMMUNICATION 8	Interval: --	Occurrences: --	Comments:	Height - Must be measured by provider (Patient cannot state)
		☑	ONC NURSING COMMUNICATION 9	Interval: --	Occurrences: --	Comments:	Weight - Must be measured by provider (Patient cannot state)
		☑	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	12-lead ECG - Study staff to perform (Contact CCAT at 713-441-9984)
		☑	ONC NURSING COMMUNICATION 11	Interval: --	Occurrences: --	Comments:	Physical exam must be performed on this date
		☑	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Indicate in Progress note a review of the subject's current B lymphoma signs and symptoms (drenching night sweats, fevers > 101°F [38.3°C], chills, unexplained weight loss of over 10% of body mass over 6 months)
		☑	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	Indicate in Progress note if Hepatomegaly is present.  If present, please include #mm below costal margin.
		☑	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Indicate in Progress note if Splenomegaly is present.  If present, please include #mm below costal margin
			Pharmacokinetic Instructions
☑	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --		☑	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --					
Cycle 1	Repeat 1 time	Cycle length: 28 days	Day 1	Perform every 1 day x1		Labs
☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		☑	MAGNESIUM LEVEL	Interval: --	Occurrences: --		☑	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		☑	URIC ACID LEVEL	Interval: --	Occurrences: --		☑	LDH	Interval: --	Occurrences: --		☑	GGT	Interval: --	Occurrences: --		☑	AMYLASE LEVEL	Interval: --	Occurrences: --		☑	LIPASE LEVEL	Interval: --	Occurrences: --		☑	CREATINE KINASE, TOTAL (CPK)	Interval: --	Occurrences: --		☑	LACTATE DEHYDROGENASE (LD) ISOENZYMES	Interval: --	Occurrences: --		☑	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	If applicable
		☑	CD3 ENUMERATION	Interval: --	Occurrences: --		☑	CD19	Interval: --	Occurrences: --		☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		☑	MANUAL DIFFERENTIAL	Interval: --	Occurrences: --	Comments:	If needed
			Nursing Orders
☑	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
		☑	ONC NURSING COMMUNICATION 6	Interval: --	Occurrences: --	Comments:	Vital signs  (blood pressure, heart rate, respiratory rate, temperature)
		☑	ONC NURSING COMMUNICATION 11	Interval: --	Occurrences: --	Comments:	Physical exam must be performed on this date
		☑	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Indicate in Progress note a review of the subject's current B lymphoma signs and symptoms (drenching night sweats, fevers > 101°F [38.3°C], chills, unexplained weight loss of over 10% of body mass over 6 months)
		☑	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	Indicate in Progress note if Hepatomegaly is present.  If present, please include #mm below costal margin.
		☑	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Indicate in Progress note if Splenomegaly is present.  If present, please include #mm below costal margin
			Pharmacokinetic Instructions
☑	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --	Comments:	For CLL ONLY
			Nursing Orders
☑	TREATMENT CONDITIONS 11	Interval: --	Occurrences: --	Comments:	Retreatment criteria for another cycle of TAK-659
o	ANC GREATER THAN or EQUAL TO 1,000/uL
o	Platelets GREATER THAN or EQUAL TO 50,000/uL
o	Hgb GREATER THAN or EQUAL TO 8.0 g/dL
o	Non-hematologic toxicity Grade LESS THAN or EQUAL TO 2:  see protocol for exceptions
			Nursing Orders
  	TREATMENT CONDITIONS	Interval: --	Occurrences: --	Comments:	CLL patients:
o	ANC GREATER THAN or EQUAL TO 1,000/µL
o	Platelet count GREATER THAN or EQUAL TO 50,000/µL 
o	Hemoglobin GREATER THAN or EQUAL TO 8 g/dL 
o	AST and ALT LESS THAN or EQUAL TO  2.5 × ULN 
o	Total bilirubin LESS THAN or EQUAL TO  1.5 × ULN 
o	Serum creatinine LESS THAN or EQUAL TO 1.5 × ULN or CrCL GREATER THAN or EQUAL TO 50 mL/min either as estimated by the Cockcroft-Gault equation or based on urine collection (12 or 24 hours)

DLBCL expansion (Cohort 2, Part B), iNHL expansion (Cohort 3, Part B), MCL expansion (Cohort 4, Part B), PTLD expansion (Cohort 5), and expanded DLBCL (Cohort 6) (Part B):
o	ANC GREATER THAN or EQUAL TO 1,000/µL
o	Platelet count GREATER THAN or EQUAL TO 75,000/µL (GREATER THAN or EQUAL TO 50,000/µL, for patients with bone marrow involvement)
o	Hemoglobin GREATER THAN or EQUAL TO 8 g/dL 
o	AST and ALT LESS THAN or EQUAL TO 2.5 × ULN
o	Total bilirubin LESS THAN or EQUAL TO 1.5 × ULN 
o	Serum creatinine LESS THAN or EQUAL TO  1.5 × ULN or CrCL GREATER THAN or EQUAL TO 50 mL/min either as estimated by the Cockcroft-Gault equation or based on urine collection (12 or 24 hours)
			Biologicals
  	PLACEHOLDER	Dose: --	Route: --		Start: S						Day 8	Perform every 1 day x1		Labs
☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		☑	MAGNESIUM LEVEL	Interval: --	Occurrences: --		☑	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		☑	URIC ACID LEVEL	Interval: --	Occurrences: --		☑	LDH	Interval: --	Occurrences: --		☑	GGT	Interval: --	Occurrences: --		☑	AMYLASE LEVEL	Interval: --	Occurrences: --		☑	LIPASE LEVEL	Interval: --	Occurrences: --		☑	CREATINE KINASE, TOTAL (CPK)	Interval: --	Occurrences: --		☑	LACTATE DEHYDROGENASE (LD) ISOENZYMES	Interval: --	Occurrences: --		☑	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	If applicable
		☑	CD3 ENUMERATION	Interval: --	Occurrences: --		☑	CD19	Interval: --	Occurrences: --		☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		☑	MANUAL DIFFERENTIAL	Interval: --	Occurrences: --	Comments:	If needed
			Nursing Orders
☑	ONC NURSING COMMUNICATION 6	Interval: --	Occurrences: --	Comments:	Vital signs  (blood pressure, heart rate, respiratory rate, temperature)
		☑	ONC NURSING COMMUNICATION 11	Interval: --	Occurrences: --	Comments:	Physical exam must be performed on this date
		☑	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Indicate in Progress note a review of the subject's current B lymphoma signs and symptoms (drenching night sweats, fevers > 101°F [38.3°C], chills, unexplained weight loss of over 10% of body mass over 6 months)
		☑	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	Indicate in Progress note if Hepatomegaly is present.  If present, please include #mm below costal margin.
		☑	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Indicate in Progress note if Splenomegaly is present.  If present, please include #mm below costal margin
				Day 15	Perform every 1 day x1		Nursing Orders
☑	ONC NURSING COMMUNICATION 6	Interval: --	Occurrences: --	Comments:	Vital signs  (blood pressure, heart rate, respiratory rate, temperature)
		☑	ONC NURSING COMMUNICATION 11	Interval: --	Occurrences: --	Comments:	Physical exam must be performed on this date
		☑	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Indicate in Progress note a review of the subject's current B lymphoma signs and symptoms (drenching night sweats, fevers > 101°F [38.3°C], chills, unexplained weight loss of over 10% of body mass over 6 months)
		☑	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	Indicate in Progress note if Hepatomegaly is present.  If present, please include #mm below costal margin.
		☑	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Indicate in Progress note if Splenomegaly is present.  If present, please include #mm below costal margin
			Pharmacokinetic Instructions
☑	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --				Day 22	Perform every 1 day x1		Labs
☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		☑	MAGNESIUM LEVEL	Interval: --	Occurrences: --		☑	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		☑	URIC ACID LEVEL	Interval: --	Occurrences: --		☑	LDH	Interval: --	Occurrences: --		☑	GGT	Interval: --	Occurrences: --		☑	AMYLASE LEVEL	Interval: --	Occurrences: --		☑	LIPASE LEVEL	Interval: --	Occurrences: --		☑	CD3 ENUMERATION	Interval: --	Occurrences: --		☑	CD19	Interval: --	Occurrences: --		☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		☑	MANUAL DIFFERENTIAL	Interval: --	Occurrences: --	Comments:	If needed
		☑	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --			Nursing Orders
☑	ONC NURSING COMMUNICATION 6	Interval: --	Occurrences: --	Comments:	Vital signs  (blood pressure, heart rate, respiratory rate, temperature)
		☑	ONC NURSING COMMUNICATION 11	Interval: --	Occurrences: --	Comments:	Physical exam must be performed on this date
		☑	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Indicate in Progress note a review of the subject's current B lymphoma signs and symptoms (drenching night sweats, fevers > 101°F [38.3°C], chills, unexplained weight loss of over 10% of body mass over 6 months)
		☑	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	Indicate in Progress note if Hepatomegaly is present.  If present, please include #mm below costal margin.
		☑	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Indicate in Progress note if Splenomegaly is present.  If present, please include #mm below costal margin
					
Cycle 2	Repeat 1 time	Cycle length: 28 days	Day 1	Perform every 1 day x1		Labs
☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		☑	MAGNESIUM LEVEL	Interval: --	Occurrences: --		☑	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		☑	URIC ACID LEVEL	Interval: --	Occurrences: --		☑	LDH	Interval: --	Occurrences: --		☑	GGT	Interval: --	Occurrences: --		☑	AMYLASE LEVEL	Interval: --	Occurrences: --		☑	LIPASE LEVEL	Interval: --	Occurrences: --		☑	CREATINE KINASE, TOTAL (CPK)	Interval: --	Occurrences: --		☑	LACTATE DEHYDROGENASE (LD) ISOENZYMES	Interval: --	Occurrences: --		☑	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	If applicable
		☑	CD3 ENUMERATION	Interval: --	Occurrences: --		☑	CD19	Interval: --	Occurrences: --		☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		☑	MANUAL DIFFERENTIAL	Interval: --	Occurrences: --	Comments:	If needed
			Nursing Orders
☑	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
		☑	ONC NURSING COMMUNICATION 6	Interval: --	Occurrences: --	Comments:	Vital signs  (blood pressure, heart rate, respiratory rate, temperature)
		☑	ONC NURSING COMMUNICATION 11	Interval: --	Occurrences: --	Comments:	Physical exam must be performed on this date
		☑	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Indicate in Progress note a review of the subject's current B lymphoma signs and symptoms (drenching night sweats, fevers > 101°F [38.3°C], chills, unexplained weight loss of over 10% of body mass over 6 months)
		☑	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	Indicate in Progress note if Hepatomegaly is present.  If present, please include #mm below costal margin.
		☑	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Indicate in Progress note if Splenomegaly is present.  If present, please include #mm below costal margin
			Pharmacokinetic Instructions
☑	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --	Comments:	For CLL ONLY
			Nursing Orders
☑	TREATMENT CONDITIONS 11	Interval: --	Occurrences: --	Comments:	Retreatment criteria for another cycle of TAK-659
o	ANC GREATER THAN or EQUAL TO 1,000/uL
o	Platelets GREATER THAN or EQUAL TO 50,000/uL
o	Hgb GREATER THAN or EQUAL TO 8.0 g/dL
o	Non-hematologic toxicity Grade LESS THAN or EQUAL TO 2:  see protocol for exceptions
			Nursing Orders
  	TREATMENT CONDITIONS 3	Interval: --	Occurrences: --	Comments:	Neutropenia (ANC):
Grade 1 (ANC < 1500 cells/mm3)                      
o	Maintain dose level
Grade 2 (ANC 1000-1,499 cells/mm3) 
o	Maintain dose level
Grade 3 (ANC 500-999 cells/mm3)
o	Withhold dose until resolved to LESS THAN or EQUAL TO Grade 1 (ANC GREATER THAN or EQUAL TO 1500 cells/mm3) or baseline, then:
o	If resolved in LESS THAN or EQUAL TO 7 days, then maintain dose level
o	If resolved in GREATER THAN 7 days, then dose reduce by 1 dose level
o	If recurred, then dose reduce by 1 dose level
Grade 4 (ANC LESS THAN 500 cells/mm3) 
o	Withhold dose until resolved to ? Grade 1 (ANC GREATER THAN or EQUAL TO 1500 cells/mm3) or baseline, then dose reduced by 1 dose level
Febrile neutropenia (ANC LESS THAN 1000 cells/mm3, fever GREATER THAN or EQUAL TO 38.5°C)
o	Dose withheld until resolved to LESS THAN Grade 1 (ANC GREATER THAN or EQUAL TO 1500 cells/mm3) or baseline and fever/infection recovered , then reduce by 1 dose level
_______________________________________________________________________________

Thrombocytopenia (Platelets):
Grade 1 (PLT LESS THAN 75,000 cells/mm3)
o	Maintain dose level
Grade 2 (PLT 50,000-74,999 cells/mm3)
o	Maintain dose level
Grade 3 (PLT 25,000-49,999 cells/mm3) 
o	Withhold dose until resolved to LESS THAN or EQUAL TO Grade 1 (PLT GREATER THAN or EQUAL TO 75,000 cells/mm3) or baseline, then:
o	If resolved in LESS THAN or EQUAL TO 7 days, then maintain dose level
o	If resolved in GREATER THAN 7 days, then dose reduce by 1 dose level
Grade 4 (PLT LESS THAN 25,000 cells/mm3)                                 
o	Withhold dose until resolved to LESS THAN or EQUAL TO Grade 1 or baseline, then reduce by 1 dose level
__________________________________________________________________________________

Grade 3 anemia                    
o	Withhold dose until resolved to LESS THAN or EQUAL TO Grade 1 or baseline, then:
o	If resolved in LESS THAN or EQUAL TO 7 days, then maintain dose level
o	If resolved in GREATER THAN 7 days, then dose reduce by 1 dose level
Grade 4 anemia
o	Withhold dose until resolved to LESS THAN or EQUAL TO Grade 1 or baseline, then reduce by 1 dose level if patient is not discontinued

TAK-659 Dose Modification for Nonhematologic Toxicities:
All Grade 3 Nonhematologic Toxicities with the EXCEPTION of:
 	Grade 3 nausea, vomiting and diarrhea resolved to ? Grade 1 or baseline within 48 hours with optimal antiemetics and antidiarrheal following standard of care
 	Transient Grade 3 fatigue (lasting < 72 hours)
 	Asymptomatic lipase elevation (< Grade 4) in the absence of significant amylase elevation (< Grade 3) considered not dose limiting following agreement between sponsor and investigators
 	Asymptomatic amylase elevation (< Grade 4) in the absence of lipase elevation (< Grade 3) considered not dose limiting following agreement between sponsor and investigators 
 	Asymptomatic Grade 3 elevation of a single liver enzyme (AST or ALT) in the absence of significant bilirubin elevation (< Grade 3) considered not dose limiting following agreement between sponsor and investigators 
 	Other asymptomatic Grade 3 laboratory abnormalities that the investigator considers not clinically significant following agreement between sponsor and investigators.

o	HOLD TAK-659 until resolution to Grade LESS THAN or EQUAL TO 1 or baseline. Reduce TAK-659 by 1 dose level

For the exceptions
o	Maintain dose level

Grade 4 Nonhematologic Toxicities
o	Consider permanently discontinuing TAK-659, except in the case where the investigator determines the patient is obtaining a clinical benefit and has discussed this with the project clinician or designee.
			Biologicals
  	PLACEHOLDER	Dose: --	Route: --		Start: S						Day 15	Perform every 1 day x1		Labs
☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		☑	MAGNESIUM LEVEL	Interval: --	Occurrences: --		☑	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		☑	URIC ACID LEVEL	Interval: --	Occurrences: --		☑	LDH	Interval: --	Occurrences: --		☑	GGT	Interval: --	Occurrences: --		☑	AMYLASE LEVEL	Interval: --	Occurrences: --		☑	LIPASE LEVEL	Interval: --	Occurrences: --		☑	CREATINE KINASE, TOTAL (CPK)	Interval: --	Occurrences: --		☑	LACTATE DEHYDROGENASE (LD) ISOENZYMES	Interval: --	Occurrences: --		☑	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	If applicable
		☑	CD3 ENUMERATION	Interval: --	Occurrences: --		☑	CD19	Interval: --	Occurrences: --		☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		☑	MANUAL DIFFERENTIAL	Interval: --	Occurrences: --	Comments:	If needed
				Day 22 - 29	Perform every 1 day x1		Imaging
☑	CT SOFT TISSUE NECK W CONTRAST	Interval: --	Occurrences: --	Comments:	If appropriate
		☑	CT CHEST W CONTRAST ABDOMEN W CONTRAST PELVIS W CONTRAST	Interval: --	Occurrences: --		☑	PET CT SKULL BASE TO MID THIGH	Interval: --	Occurrences: --			Imaging
  	PET CT SKULL BASE TO MID THIGH	Interval: --	Occurrences: --	Comments:	o	NOT FOR CLL
o	ONLY FOR Diffuse Large B Cell Lymphoma (DLBCL), indolent Non Hodgkin Lymphoma (iNHL), Mantle Cell Lymphoma (MCL), Post Transplant Lymphoproliferative Disorder (PTLD)
o	ONLY if screening FDG-PET was positive
					
Cycle 3	Repeat 1 time	Cycle length: 28 days	Day 1	Perform every 1 day x1		Labs
☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		☑	MAGNESIUM LEVEL	Interval: --	Occurrences: --		☑	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		☑	URIC ACID LEVEL	Interval: --	Occurrences: --		☑	LDH	Interval: --	Occurrences: --		☑	GGT	Interval: --	Occurrences: --		☑	AMYLASE LEVEL	Interval: --	Occurrences: --		☑	LIPASE LEVEL	Interval: --	Occurrences: --		☑	CREATINE KINASE, TOTAL (CPK)	Interval: --	Occurrences: --		☑	LACTATE DEHYDROGENASE (LD) ISOENZYMES	Interval: --	Occurrences: --		☑	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	If applicable
		☑	CD3 ENUMERATION	Interval: --	Occurrences: --		☑	CD19	Interval: --	Occurrences: --		☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		☑	MANUAL DIFFERENTIAL	Interval: --	Occurrences: --	Comments:	If needed
		☑	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --			Nursing Orders
☑	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
		☑	ONC NURSING COMMUNICATION 6	Interval: --	Occurrences: --	Comments:	Vital signs  (blood pressure, heart rate, respiratory rate, temperature)
		☑	ONC NURSING COMMUNICATION 11	Interval: --	Occurrences: --	Comments:	Physical exam must be performed on this date
		☑	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Indicate in Progress note a review of the subject's current B lymphoma signs and symptoms (drenching night sweats, fevers > 101°F [38.3°C], chills, unexplained weight loss of over 10% of body mass over 6 months)
		☑	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	Indicate in Progress note if Hepatomegaly is present.  If present, please include #mm below costal margin.
		☑	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Indicate in Progress note if Splenomegaly is present.  If present, please include #mm below costal margin
			Pharmacokinetic Instructions
☑	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --	Comments:	For CLL ONLY
			Nursing Orders
☑	TREATMENT CONDITIONS 11	Interval: --	Occurrences: --	Comments:	Retreatment criteria for another cycle of TAK-659
o	ANC GREATER THAN or EQUAL TO 1,000/uL
o	Platelets GREATER THAN or EQUAL TO 50,000/uL
o	Hgb GREATER THAN or EQUAL TO 8.0 g/dL
o	Non-hematologic toxicity Grade LESS THAN or EQUAL TO 2:  see protocol for exceptions
			Nursing Orders
  	TREATMENT CONDITIONS 3	Interval: --	Occurrences: --	Comments:	Neutropenia (ANC):
Grade 1 (ANC < 1500 cells/mm3)                      
o	Maintain dose level
Grade 2 (ANC 1000-1,499 cells/mm3) 
o	Maintain dose level
Grade 3 (ANC 500-999 cells/mm3)
o	Withhold dose until resolved to LESS THAN or EQUAL TO Grade 1 (ANC GREATER THAN or EQUAL TO 1500 cells/mm3) or baseline, then:
o	If resolved in LESS THAN or EQUAL TO 7 days, then maintain dose level
o	If resolved in GREATER THAN 7 days, then dose reduce by 1 dose level
o	If recurred, then dose reduce by 1 dose level
Grade 4 (ANC LESS THAN 500 cells/mm3) 
o	Withhold dose until resolved to ? Grade 1 (ANC GREATER THAN or EQUAL TO 1500 cells/mm3) or baseline, then dose reduced by 1 dose level
Febrile neutropenia (ANC LESS THAN 1000 cells/mm3, fever GREATER THAN or EQUAL TO 38.5°C)
o	Dose withheld until resolved to LESS THAN Grade 1 (ANC GREATER THAN or EQUAL TO 1500 cells/mm3) or baseline and fever/infection recovered , then reduce by 1 dose level
_______________________________________________________________________________

Thrombocytopenia (Platelets):
Grade 1 (PLT LESS THAN 75,000 cells/mm3)
o	Maintain dose level
Grade 2 (PLT 50,000-74,999 cells/mm3)
o	Maintain dose level
Grade 3 (PLT 25,000-49,999 cells/mm3) 
o	Withhold dose until resolved to LESS THAN or EQUAL TO Grade 1 (PLT GREATER THAN or EQUAL TO 75,000 cells/mm3) or baseline, then:
o	If resolved in LESS THAN or EQUAL TO 7 days, then maintain dose level
o	If resolved in GREATER THAN 7 days, then dose reduce by 1 dose level
Grade 4 (PLT LESS THAN 25,000 cells/mm3)                                 
o	Withhold dose until resolved to LESS THAN or EQUAL TO Grade 1 or baseline, then reduce by 1 dose level
__________________________________________________________________________________

Grade 3 anemia                    
o	Withhold dose until resolved to LESS THAN or EQUAL TO Grade 1 or baseline, then:
o	If resolved in LESS THAN or EQUAL TO 7 days, then maintain dose level
o	If resolved in GREATER THAN 7 days, then dose reduce by 1 dose level
Grade 4 anemia
o	Withhold dose until resolved to LESS THAN or EQUAL TO Grade 1 or baseline, then reduce by 1 dose level if patient is not discontinued

TAK-659 Dose Modification for Nonhematologic Toxicities:
All Grade 3 Nonhematologic Toxicities with the EXCEPTION of:
 	Grade 3 nausea, vomiting and diarrhea resolved to ? Grade 1 or baseline within 48 hours with optimal antiemetics and antidiarrheal following standard of care
 	Transient Grade 3 fatigue (lasting < 72 hours)
 	Asymptomatic lipase elevation (< Grade 4) in the absence of significant amylase elevation (< Grade 3) considered not dose limiting following agreement between sponsor and investigators
 	Asymptomatic amylase elevation (< Grade 4) in the absence of lipase elevation (< Grade 3) considered not dose limiting following agreement between sponsor and investigators 
 	Asymptomatic Grade 3 elevation of a single liver enzyme (AST or ALT) in the absence of significant bilirubin elevation (< Grade 3) considered not dose limiting following agreement between sponsor and investigators 
 	Other asymptomatic Grade 3 laboratory abnormalities that the investigator considers not clinically significant following agreement between sponsor and investigators.

o	HOLD TAK-659 until resolution to Grade LESS THAN or EQUAL TO 1 or baseline. Reduce TAK-659 by 1 dose level

For the exceptions
o	Maintain dose level

Grade 4 Nonhematologic Toxicities
o	Consider permanently discontinuing TAK-659, except in the case where the investigator determines the patient is obtaining a clinical benefit and has discussed this with the project clinician or designee.
			Biologicals
  	PLACEHOLDER	Dose: --	Route: --		Start: S							
Cycle 4	Repeat 1 time	Cycle length: 28 days	Day 1	Perform every 1 day x1		Labs
☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		☑	MAGNESIUM LEVEL	Interval: --	Occurrences: --		☑	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		☑	URIC ACID LEVEL	Interval: --	Occurrences: --		☑	LDH	Interval: --	Occurrences: --		☑	GGT	Interval: --	Occurrences: --		☑	AMYLASE LEVEL	Interval: --	Occurrences: --		☑	LIPASE LEVEL	Interval: --	Occurrences: --		☑	CREATINE KINASE, TOTAL (CPK)	Interval: --	Occurrences: --		☑	LACTATE DEHYDROGENASE (LD) ISOENZYMES	Interval: --	Occurrences: --		☑	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	If applicable
		☑	CD3 ENUMERATION	Interval: --	Occurrences: --		☑	CD19	Interval: --	Occurrences: --		☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		☑	MANUAL DIFFERENTIAL	Interval: --	Occurrences: --	Comments:	If needed
		☑	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --			Nursing Orders
☑	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
		☑	ONC NURSING COMMUNICATION 6	Interval: --	Occurrences: --	Comments:	Vital signs  (blood pressure, heart rate, respiratory rate, temperature)
		☑	ONC NURSING COMMUNICATION 11	Interval: --	Occurrences: --	Comments:	Physical exam must be performed on this date
		☑	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Indicate in Progress note a review of the subject's current B lymphoma signs and symptoms (drenching night sweats, fevers > 101°F [38.3°C], chills, unexplained weight loss of over 10% of body mass over 6 months)
		☑	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	Indicate in Progress note if Hepatomegaly is present.  If present, please include #mm below costal margin.
		☑	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Indicate in Progress note if Splenomegaly is present.  If present, please include #mm below costal margin
			Pharmacokinetic Instructions
☑	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --	Comments:	For CLL ONLY
			Nursing Orders
☑	TREATMENT CONDITIONS 11	Interval: --	Occurrences: --	Comments:	Retreatment criteria for another cycle of TAK-659
o	ANC GREATER THAN or EQUAL TO 1,000/uL
o	Platelets GREATER THAN or EQUAL TO 50,000/uL
o	Hgb GREATER THAN or EQUAL TO 8.0 g/dL
o	Non-hematologic toxicity Grade LESS THAN or EQUAL TO 2:  see protocol for exceptions
			Nursing Orders
  	TREATMENT CONDITIONS 3	Interval: --	Occurrences: --	Comments:	Neutropenia (ANC):
Grade 1 (ANC < 1500 cells/mm3)                      
o	Maintain dose level
Grade 2 (ANC 1000-1,499 cells/mm3) 
o	Maintain dose level
Grade 3 (ANC 500-999 cells/mm3)
o	Withhold dose until resolved to LESS THAN or EQUAL TO Grade 1 (ANC GREATER THAN or EQUAL TO 1500 cells/mm3) or baseline, then:
o	If resolved in LESS THAN or EQUAL TO 7 days, then maintain dose level
o	If resolved in GREATER THAN 7 days, then dose reduce by 1 dose level
o	If recurred, then dose reduce by 1 dose level
Grade 4 (ANC LESS THAN 500 cells/mm3) 
o	Withhold dose until resolved to ? Grade 1 (ANC GREATER THAN or EQUAL TO 1500 cells/mm3) or baseline, then dose reduced by 1 dose level
Febrile neutropenia (ANC LESS THAN 1000 cells/mm3, fever GREATER THAN or EQUAL TO 38.5°C)
o	Dose withheld until resolved to LESS THAN Grade 1 (ANC GREATER THAN or EQUAL TO 1500 cells/mm3) or baseline and fever/infection recovered , then reduce by 1 dose level
_______________________________________________________________________________

Thrombocytopenia (Platelets):
Grade 1 (PLT LESS THAN 75,000 cells/mm3)
o	Maintain dose level
Grade 2 (PLT 50,000-74,999 cells/mm3)
o	Maintain dose level
Grade 3 (PLT 25,000-49,999 cells/mm3) 
o	Withhold dose until resolved to LESS THAN or EQUAL TO Grade 1 (PLT GREATER THAN or EQUAL TO 75,000 cells/mm3) or baseline, then:
o	If resolved in LESS THAN or EQUAL TO 7 days, then maintain dose level
o	If resolved in GREATER THAN 7 days, then dose reduce by 1 dose level
Grade 4 (PLT LESS THAN 25,000 cells/mm3)                                 
o	Withhold dose until resolved to LESS THAN or EQUAL TO Grade 1 or baseline, then reduce by 1 dose level
__________________________________________________________________________________

Grade 3 anemia                    
o	Withhold dose until resolved to LESS THAN or EQUAL TO Grade 1 or baseline, then:
o	If resolved in LESS THAN or EQUAL TO 7 days, then maintain dose level
o	If resolved in GREATER THAN 7 days, then dose reduce by 1 dose level
Grade 4 anemia
o	Withhold dose until resolved to LESS THAN or EQUAL TO Grade 1 or baseline, then reduce by 1 dose level if patient is not discontinued

TAK-659 Dose Modification for Nonhematologic Toxicities:
All Grade 3 Nonhematologic Toxicities with the EXCEPTION of:
 	Grade 3 nausea, vomiting and diarrhea resolved to ? Grade 1 or baseline within 48 hours with optimal antiemetics and antidiarrheal following standard of care
 	Transient Grade 3 fatigue (lasting < 72 hours)
 	Asymptomatic lipase elevation (< Grade 4) in the absence of significant amylase elevation (< Grade 3) considered not dose limiting following agreement between sponsor and investigators
 	Asymptomatic amylase elevation (< Grade 4) in the absence of lipase elevation (< Grade 3) considered not dose limiting following agreement between sponsor and investigators 
 	Asymptomatic Grade 3 elevation of a single liver enzyme (AST or ALT) in the absence of significant bilirubin elevation (< Grade 3) considered not dose limiting following agreement between sponsor and investigators 
 	Other asymptomatic Grade 3 laboratory abnormalities that the investigator considers not clinically significant following agreement between sponsor and investigators.

o	HOLD TAK-659 until resolution to Grade LESS THAN or EQUAL TO 1 or baseline. Reduce TAK-659 by 1 dose level

For the exceptions
o	Maintain dose level

Grade 4 Nonhematologic Toxicities
o	Consider permanently discontinuing TAK-659, except in the case where the investigator determines the patient is obtaining a clinical benefit and has discussed this with the project clinician or designee.
			Biologicals
  	PLACEHOLDER	Dose: --	Route: --		Start: S						Day 22 - 29	Perform every 1 day x1		Imaging
☑	CT SOFT TISSUE NECK W CONTRAST	Interval: --	Occurrences: --	Comments:	If appropriate
		☑	CT CHEST W CONTRAST ABDOMEN W CONTRAST PELVIS W CONTRAST	Interval: --	Occurrences: --		☑	PET CT SKULL BASE TO MID THIGH	Interval: --	Occurrences: --			Imaging
  	PET CT SKULL BASE TO MID THIGH	Interval: --	Occurrences: --	Comments:	o	NOT FOR CLL
o	ONLY FOR Diffuse Large B Cell Lymphoma (DLBCL), indolent Non Hodgkin Lymphoma (iNHL), Mantle Cell Lymphoma (MCL), Post Transplant Lymphoproliferative Disorder (PTLD)
o	ONLY if screening FDG-PET was positive
					
Cycle 5	Repeat 1 time	Cycle length: 28 days	Day 1	Perform every 1 day x1		Labs
☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		☑	MAGNESIUM LEVEL	Interval: --	Occurrences: --		☑	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		☑	URIC ACID LEVEL	Interval: --	Occurrences: --		☑	LDH	Interval: --	Occurrences: --		☑	GGT	Interval: --	Occurrences: --		☑	AMYLASE LEVEL	Interval: --	Occurrences: --		☑	LIPASE LEVEL	Interval: --	Occurrences: --		☑	CREATINE KINASE, TOTAL (CPK)	Interval: --	Occurrences: --		☑	LACTATE DEHYDROGENASE (LD) ISOENZYMES	Interval: --	Occurrences: --		☑	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	If applicable
		☑	CD3 ENUMERATION	Interval: --	Occurrences: --		☑	CD19	Interval: --	Occurrences: --		☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		☑	MANUAL DIFFERENTIAL	Interval: --	Occurrences: --	Comments:	If needed
		☑	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --			Nursing Orders
☑	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
		☑	ONC NURSING COMMUNICATION 6	Interval: --	Occurrences: --	Comments:	Vital signs  (blood pressure, heart rate, respiratory rate, temperature)
		☑	ONC NURSING COMMUNICATION 11	Interval: --	Occurrences: --	Comments:	Physical exam must be performed on this date
		☑	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Indicate in Progress note a review of the subject's current B lymphoma signs and symptoms (drenching night sweats, fevers > 101°F [38.3°C], chills, unexplained weight loss of over 10% of body mass over 6 months)
		☑	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	Indicate in Progress note if Hepatomegaly is present.  If present, please include #mm below costal margin.
		☑	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Indicate in Progress note if Splenomegaly is present.  If present, please include #mm below costal margin
			Pharmacokinetic Instructions
☑	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --	Comments:	For CLL ONLY
			Nursing Orders
☑	TREATMENT CONDITIONS 11	Interval: --	Occurrences: --	Comments:	Retreatment criteria for another cycle of TAK-659
o	ANC GREATER THAN or EQUAL TO 1,000/uL
o	Platelets GREATER THAN or EQUAL TO 50,000/uL
o	Hgb GREATER THAN or EQUAL TO 8.0 g/dL
o	Non-hematologic toxicity Grade LESS THAN or EQUAL TO 2:  see protocol for exceptions
			Nursing Orders
  	TREATMENT CONDITIONS 3	Interval: --	Occurrences: --	Comments:	Neutropenia (ANC):
Grade 1 (ANC < 1500 cells/mm3)                      
o	Maintain dose level
Grade 2 (ANC 1000-1,499 cells/mm3) 
o	Maintain dose level
Grade 3 (ANC 500-999 cells/mm3)
o	Withhold dose until resolved to LESS THAN or EQUAL TO Grade 1 (ANC GREATER THAN or EQUAL TO 1500 cells/mm3) or baseline, then:
o	If resolved in LESS THAN or EQUAL TO 7 days, then maintain dose level
o	If resolved in GREATER THAN 7 days, then dose reduce by 1 dose level
o	If recurred, then dose reduce by 1 dose level
Grade 4 (ANC LESS THAN 500 cells/mm3) 
o	Withhold dose until resolved to ? Grade 1 (ANC GREATER THAN or EQUAL TO 1500 cells/mm3) or baseline, then dose reduced by 1 dose level
Febrile neutropenia (ANC LESS THAN 1000 cells/mm3, fever GREATER THAN or EQUAL TO 38.5°C)
o	Dose withheld until resolved to LESS THAN Grade 1 (ANC GREATER THAN or EQUAL TO 1500 cells/mm3) or baseline and fever/infection recovered , then reduce by 1 dose level
_______________________________________________________________________________

Thrombocytopenia (Platelets):
Grade 1 (PLT LESS THAN 75,000 cells/mm3)
o	Maintain dose level
Grade 2 (PLT 50,000-74,999 cells/mm3)
o	Maintain dose level
Grade 3 (PLT 25,000-49,999 cells/mm3) 
o	Withhold dose until resolved to LESS THAN or EQUAL TO Grade 1 (PLT GREATER THAN or EQUAL TO 75,000 cells/mm3) or baseline, then:
o	If resolved in LESS THAN or EQUAL TO 7 days, then maintain dose level
o	If resolved in GREATER THAN 7 days, then dose reduce by 1 dose level
Grade 4 (PLT LESS THAN 25,000 cells/mm3)                                 
o	Withhold dose until resolved to LESS THAN or EQUAL TO Grade 1 or baseline, then reduce by 1 dose level
__________________________________________________________________________________

Grade 3 anemia                    
o	Withhold dose until resolved to LESS THAN or EQUAL TO Grade 1 or baseline, then:
o	If resolved in LESS THAN or EQUAL TO 7 days, then maintain dose level
o	If resolved in GREATER THAN 7 days, then dose reduce by 1 dose level
Grade 4 anemia
o	Withhold dose until resolved to LESS THAN or EQUAL TO Grade 1 or baseline, then reduce by 1 dose level if patient is not discontinued

TAK-659 Dose Modification for Nonhematologic Toxicities:
All Grade 3 Nonhematologic Toxicities with the EXCEPTION of:
 	Grade 3 nausea, vomiting and diarrhea resolved to ? Grade 1 or baseline within 48 hours with optimal antiemetics and antidiarrheal following standard of care
 	Transient Grade 3 fatigue (lasting < 72 hours)
 	Asymptomatic lipase elevation (< Grade 4) in the absence of significant amylase elevation (< Grade 3) considered not dose limiting following agreement between sponsor and investigators
 	Asymptomatic amylase elevation (< Grade 4) in the absence of lipase elevation (< Grade 3) considered not dose limiting following agreement between sponsor and investigators 
 	Asymptomatic Grade 3 elevation of a single liver enzyme (AST or ALT) in the absence of significant bilirubin elevation (< Grade 3) considered not dose limiting following agreement between sponsor and investigators 
 	Other asymptomatic Grade 3 laboratory abnormalities that the investigator considers not clinically significant following agreement between sponsor and investigators.

o	HOLD TAK-659 until resolution to Grade LESS THAN or EQUAL TO 1 or baseline. Reduce TAK-659 by 1 dose level

For the exceptions
o	Maintain dose level

Grade 4 Nonhematologic Toxicities
o	Consider permanently discontinuing TAK-659, except in the case where the investigator determines the patient is obtaining a clinical benefit and has discussed this with the project clinician or designee.
			Biologicals
  	PLACEHOLDER	Dose: --	Route: --		Start: S							
Cycle 6	Repeat 1 time	Cycle length: 28 days	Day 1	Perform every 1 day x1		Labs
☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		☑	MAGNESIUM LEVEL	Interval: --	Occurrences: --		☑	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		☑	URIC ACID LEVEL	Interval: --	Occurrences: --		☑	LDH	Interval: --	Occurrences: --		☑	GGT	Interval: --	Occurrences: --		☑	AMYLASE LEVEL	Interval: --	Occurrences: --		☑	LIPASE LEVEL	Interval: --	Occurrences: --		☑	CREATINE KINASE, TOTAL (CPK)	Interval: --	Occurrences: --		☑	LACTATE DEHYDROGENASE (LD) ISOENZYMES	Interval: --	Occurrences: --		☑	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	If applicable
		☑	CD3 ENUMERATION	Interval: --	Occurrences: --		☑	CD19	Interval: --	Occurrences: --		☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		☑	MANUAL DIFFERENTIAL	Interval: --	Occurrences: --	Comments:	If needed
		☑	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --			Nursing Orders
☑	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
		☑	ONC NURSING COMMUNICATION 6	Interval: --	Occurrences: --	Comments:	Vital signs  (blood pressure, heart rate, respiratory rate, temperature)
		☑	ONC NURSING COMMUNICATION 11	Interval: --	Occurrences: --	Comments:	Physical exam must be performed on this date
		☑	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Indicate in Progress note a review of the subject's current B lymphoma signs and symptoms (drenching night sweats, fevers > 101°F [38.3°C], chills, unexplained weight loss of over 10% of body mass over 6 months)
		☑	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	Indicate in Progress note if Hepatomegaly is present.  If present, please include #mm below costal margin.
		☑	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Indicate in Progress note if Splenomegaly is present.  If present, please include #mm below costal margin
			Pharmacokinetic Instructions
☑	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --	Comments:	For CLL ONLY
			Nursing Orders
☑	TREATMENT CONDITIONS 11	Interval: --	Occurrences: --	Comments:	Retreatment criteria for another cycle of TAK-659
o	ANC GREATER THAN or EQUAL TO 1,000/uL
o	Platelets GREATER THAN or EQUAL TO 50,000/uL
o	Hgb GREATER THAN or EQUAL TO 8.0 g/dL
o	Non-hematologic toxicity Grade LESS THAN or EQUAL TO 2:  see protocol for exceptions
			Nursing Orders
  	TREATMENT CONDITIONS 3	Interval: --	Occurrences: --	Comments:	Neutropenia (ANC):
Grade 1 (ANC < 1500 cells/mm3)                      
o	Maintain dose level
Grade 2 (ANC 1000-1,499 cells/mm3) 
o	Maintain dose level
Grade 3 (ANC 500-999 cells/mm3)
o	Withhold dose until resolved to LESS THAN or EQUAL TO Grade 1 (ANC GREATER THAN or EQUAL TO 1500 cells/mm3) or baseline, then:
o	If resolved in LESS THAN or EQUAL TO 7 days, then maintain dose level
o	If resolved in GREATER THAN 7 days, then dose reduce by 1 dose level
o	If recurred, then dose reduce by 1 dose level
Grade 4 (ANC LESS THAN 500 cells/mm3) 
o	Withhold dose until resolved to ? Grade 1 (ANC GREATER THAN or EQUAL TO 1500 cells/mm3) or baseline, then dose reduced by 1 dose level
Febrile neutropenia (ANC LESS THAN 1000 cells/mm3, fever GREATER THAN or EQUAL TO 38.5°C)
o	Dose withheld until resolved to LESS THAN Grade 1 (ANC GREATER THAN or EQUAL TO 1500 cells/mm3) or baseline and fever/infection recovered , then reduce by 1 dose level
_______________________________________________________________________________

Thrombocytopenia (Platelets):
Grade 1 (PLT LESS THAN 75,000 cells/mm3)
o	Maintain dose level
Grade 2 (PLT 50,000-74,999 cells/mm3)
o	Maintain dose level
Grade 3 (PLT 25,000-49,999 cells/mm3) 
o	Withhold dose until resolved to LESS THAN or EQUAL TO Grade 1 (PLT GREATER THAN or EQUAL TO 75,000 cells/mm3) or baseline, then:
o	If resolved in LESS THAN or EQUAL TO 7 days, then maintain dose level
o	If resolved in GREATER THAN 7 days, then dose reduce by 1 dose level
Grade 4 (PLT LESS THAN 25,000 cells/mm3)                                 
o	Withhold dose until resolved to LESS THAN or EQUAL TO Grade 1 or baseline, then reduce by 1 dose level
__________________________________________________________________________________

Grade 3 anemia                    
o	Withhold dose until resolved to LESS THAN or EQUAL TO Grade 1 or baseline, then:
o	If resolved in LESS THAN or EQUAL TO 7 days, then maintain dose level
o	If resolved in GREATER THAN 7 days, then dose reduce by 1 dose level
Grade 4 anemia
o	Withhold dose until resolved to LESS THAN or EQUAL TO Grade 1 or baseline, then reduce by 1 dose level if patient is not discontinued

TAK-659 Dose Modification for Nonhematologic Toxicities:
All Grade 3 Nonhematologic Toxicities with the EXCEPTION of:
 	Grade 3 nausea, vomiting and diarrhea resolved to ? Grade 1 or baseline within 48 hours with optimal antiemetics and antidiarrheal following standard of care
 	Transient Grade 3 fatigue (lasting < 72 hours)
 	Asymptomatic lipase elevation (< Grade 4) in the absence of significant amylase elevation (< Grade 3) considered not dose limiting following agreement between sponsor and investigators
 	Asymptomatic amylase elevation (< Grade 4) in the absence of lipase elevation (< Grade 3) considered not dose limiting following agreement between sponsor and investigators 
 	Asymptomatic Grade 3 elevation of a single liver enzyme (AST or ALT) in the absence of significant bilirubin elevation (< Grade 3) considered not dose limiting following agreement between sponsor and investigators 
 	Other asymptomatic Grade 3 laboratory abnormalities that the investigator considers not clinically significant following agreement between sponsor and investigators.

o	HOLD TAK-659 until resolution to Grade LESS THAN or EQUAL TO 1 or baseline. Reduce TAK-659 by 1 dose level

For the exceptions
o	Maintain dose level

Grade 4 Nonhematologic Toxicities
o	Consider permanently discontinuing TAK-659, except in the case where the investigator determines the patient is obtaining a clinical benefit and has discussed this with the project clinician or designee.
			Biologicals
  	PLACEHOLDER	Dose: --	Route: --		Start: S						Day 22 - 29	Perform every 1 day x1		Imaging
☑	CT SOFT TISSUE NECK W CONTRAST	Interval: --	Occurrences: --	Comments:	If appropriate
		☑	CT CHEST W CONTRAST ABDOMEN W CONTRAST PELVIS W CONTRAST	Interval: --	Occurrences: --		☑	PET CT SKULL BASE TO MID THIGH	Interval: --	Occurrences: --			Imaging
  	PET CT SKULL BASE TO MID THIGH	Interval: --	Occurrences: --	Comments:	o	NOT FOR CLL
o	ONLY FOR Diffuse Large B Cell Lymphoma (DLBCL), indolent Non Hodgkin Lymphoma (iNHL), Mantle Cell Lymphoma (MCL), Post Transplant Lymphoproliferative Disorder (PTLD)
o	ONLY if screening FDG-PET was positive
					
End of Study	Repeat 1 time	Cycle length: 28 days	Day 1	Perform every 1 day x1		Nursing Orders
☑	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
		☑	ONC NURSING COMMUNICATION 6	Interval: --	Occurrences: --	Comments:	Vital signs  (blood pressure, heart rate, respiratory rate, temperature)
		☑	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	12-lead ECG - Study staff to perform (Contact CCAT at 713-441-9984)
		☑	ONC NURSING COMMUNICATION 11	Interval: --	Occurrences: --	Comments:	Physical exam must be performed on this date
		☑	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Indicate in Progress note a review of the subject's current B lymphoma signs and symptoms (drenching night sweats, fevers > 101°F [38.3°C], chills, unexplained weight loss of over 10% of body mass over 6 months)
		☑	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	Indicate in Progress note if Hepatomegaly is present.  If present, please include #mm below costal margin.
		☑	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Indicate in Progress note if Splenomegaly is present.  If present, please include #mm below costal margin
				Day 22 - 29	Perform every 1 day x1		Imaging
☑	CT SOFT TISSUE NECK W CONTRAST	Interval: --	Occurrences: --	Comments:	If appropriate
		☑	CT CHEST W CONTRAST ABDOMEN W CONTRAST PELVIS W CONTRAST	Interval: --	Occurrences: --		☑	PET CT SKULL BASE TO MID THIGH	Interval: --	Occurrences: --			Imaging
  	PET CT SKULL BASE TO MID THIGH	Interval: --	Occurrences: --	Comments:	o	NOT FOR CLL
o	ONLY FOR Diffuse Large B Cell Lymphoma (DLBCL), indolent Non Hodgkin Lymphoma (iNHL), Mantle Cell Lymphoma (MCL), Post Transplant Lymphoproliferative Disorder (PTLD)
o	ONLY if screening FDG-PET was positive