MT2017-45: CAR-T Cell Therapy for Heme Malignancies | NCT03642626

NCT03642626

ID	Type	Description	Link
MT2017-45	Other Identifier	University of Minnesota Masonic Cancer Center
NCI-2020-04527	Registry Identifier	CTRP

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Intervention Names
ARM A: Refractory/relapsed B-cell acute lymphoblastic leukemia (ALL)	Experimental	Drug: KYMRIAH Drug: Fludarabine 30mg/m2 4 doses Drug: Cyclophosphamide 500 mg/m2; 2 doses
ARM B: Yescarta for Refractory diffuse large B cell lymphoma (DLBCL)	Experimental	Drug: YESCARTA Drug: Fludarabine 30mg/m2 3 doses Drug: Cyclophosphamide 500 mg/m2; 3 doses
ARM C: Kymriah for Refractory diffuse large B cell lymphoma (DLBCL)	Experimental	Drug: KYMRIAH Drug: Fludarabine 25mg/m2 3 days Drug: Cyclophosphamide 250 mg/m2; 3 days
Arm D: Tecartus CAR-T product for Mantle Cell Leukemia (MCL)	Experimental	Drug: Fludarabine 30mg/m2 3 doses Drug: Cyclophosphamide 500 mg/m2; 3 doses Drug: Tecartus
Arm E: Breyanzi for relapsed or refractory large B-cell lymphoma (RLBCL)	Experimental	Drug: Fludarabine 30mg/m2 3 doses Drug: Cyclophosphamide 500 mg/m2; 3 doses Drug: Breyanzi Injectable Product
Arm F: Abecma for relapsed or refractory multiple myeloma

Interventions

Name	Type	Description	Arm Group Labels	Other Names
KYMRIAH	Drug	FDA approved CD19-directed genetically modified autologous T cell immunotherapy comprised of autologous T cells	ARM A: Refractory/relapsed B-cell acute lymphoblastic leukemia (ALL)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Arms B & C&D& E&F: Overall Response Rate (ORR)	ORR defined by complete response + partial response by Lugano	Day 100
Arm A & E: MRD-negative CR (or CRi)	Percentage of patients with MRD-negative Complete Response CR (or CRi)	Day 28

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Patients Developing Grade 3 or 4 ICANS	Percentage of patients developing grade 3 or 4 ICANS	Day 28
Treatment Related Mortality (TRM)	Incidence of treatment related mortality (in absence of disease relapse/progression)

Eligibility Module

Eligibility Criteria

ARM A (Kymriah) and Arm G (Tecartus) :Refractory/relapsed B-cell acute lymphoblastic leukemia expressing CD19

Inclusion Criteria:

Age and Disease Status
- Must be age 0-25 years (for Arm A Kymriah) or >18 years (Arm G Tecartus)
- Disease status: Relapsed and refractory pediatric B-cell ALL defined by one of these:
  - Primary induction failure with no complete remission after ≥2 cycles of induction chemotherapy, or
  - Patients with persistent minimal residual disease (MRD >0.01% by flow cytometry or persistent by cytogenetic or molecular assays) after ≥2 cycles of consolidation chemotherapy, or
  - Patients in 2nd or greater relapse of B-ALL or
  - Patients with persistent CNS leukemia, or
  - Down Syndrome or other congenital diseases assuming that they fit the criteria for second or greater relapse or refractory leukemia, or
  - Patients with Ph+ ALL are eligible if theywho have failed or are intolerant to two lines of TKI assuming they fit the criteria for second or greater relapse or are considered refractory.
Performance Status

* Arm A: Karnofsky (age ≥16 years) or Lansky (age < 16 years) performance status ≥ 50% at screening; Arm G: ECOG 0, 1 or 2
Organ Function
- Renal function defined as:
  - A serum creatinine of ≤1.5 x ULN OR
  - eGFR ≥ 50 mL/min/1.73 m2
- Liver function defined as:
  
  ** ALT ≤ 5 times the ULN for age (unless due to disease)
  
  ** Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
- Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation SpO2 > 91% on room air
- Hemodynamically stable and LVEF ≥ 45% confirmed by echocardiogram or MUGA
Other Inclusion Criteria
- Life expectancy ≥12 weeks
- Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment.
- Written voluntary consent (adults) or parental/guardian consent (minors or adults with diminished capacity) prior to the performance of any research related tests or procedures.

Exclusion Criteria:

Pregnant or breastfeeding - Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
Patients with Burkitt's lymphoma/leukemia (i.e. patients with mature B-cell ALL, leukemia with B-cell [sIg positive and kappa or lambda restricted positivity] ALL, with FAB L3 morphology and /or a MYC translocation)
CNS 2A
CAR-T is not indicated for the treatment of patients with primary central nervous system lymphoma.
Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD). All GVHD medication must be stopped 2 weeks prior to apheresis.
Uncontrolled active hepatitis B or hepatitis C
Active HIV infection
Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
Unstable angina and/or myocardial infarction within 1 month prior to CAR-T infusion
Investigational medicinal product within the last 7 days prior to apheresis or CAR-T infusion
Intolerance to the excipients of the CAR-T cell product
Any immunosuppressive medication must be stopped ≥ 2 weeks prior to enrollment.
Patient has taken one of the prohibited concomitant medications within the timeframe outlined in section 6.1

ARM B: Yescarta for Relapsed or Refractory diffuse large B cell lymphoma

Inclusion Criteria:

Age and Disease Status
- Adult patients (age ≥ 18 years)Patients must be ≥18 years of age
- One of the following histologies and expression of CD19 by tumor cells:
  
  ** diffuse large B-cell lymphoma (DLBCL) not otherwise specified, or
  
  ** primary mediastinal large B-cell lymphoma, or
  
  ** high grade B-cell lymphoma, or
  
  ** DLBCL arising from follicular lymphoma
- Disease status:
  
  ** Chemotherapy refractory disease after ≥2 lines of chemotherapy, or
  
  ** Relapsed with no remission after ≥1 lines of salvage chemotherapy, or
  
  ** Relapsed following autologous HCT (and failed at least 2 prior lines of therapy including high dose chemotherapy). If salvage therapy is given post autoHCT, the subject must have no response or relapse after the last line of therapy
- Measurable disease at time of apheresis: Nodal lesions or extranodal lesion
- ECOG performance status 0-2
- ALC >/=100/uL at screening (prior to apheresis)
- Renal function defined as:
  
  ** A serum creatinine of ≤1.5 x ULN OR
  
  ** eGFR ≥ 50 mL/min/1.73 m2
- Liver function defined as:
  - ALT ≤ 5 times the ULN for age (unless due to disease)
  - Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
- Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation SpO2 > 91% on room air
- Hemodynamically stable and LVEF ≥ 45% confirmed by echocardiogram or MUGA
- Adequate bone marrow reserve (unless marrow infiltrated by disease) defined as :
  - Absolute neutrophil count (ANC) > 1.000/mm3 (only for NHL)
  - Platelets ≥ 50.000/mm3 (transfusion support can be provided)
  - Hemoglobin >8.0 mg/dl (transfusion support can be provided)
- Life expectancy ≥12 weeks
- Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment.
- Written voluntary consent (adults) or parental/guardian consent (minors or adults with diminished capacity) prior to the performance of any research related tests or procedures.

Exclusion Criteria:

Pregnant or breastfeeding - Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
Active CNS involvement by malignancy (no evidence of disease in CSF by flow cytometry) CAR-T is not indicated for the treatment of patients with primary central nervous system lymphoma.
Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD). All GVHD medication must be stopped 2 weeks prior to apheresis.
Uncontrolled active hepatitis B or hepatitis C
Active HIV infection (controlled HIV is permissible)
Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
Unstable angina and/or myocardial infarction within 1 month prior to CAR-T infusion
Investigational medicinal product within the last 7 days prior to apheresis or CAR-T infusion
Intolerance to the excipients of the CAR-T cell product
Any immunosuppressive medication must be stopped ≥ 2 weeks prior to apheresis.
Patient has taken one of the prohibited concomitant medications within the timeframe.

ARM C: Kymriah for rRelapsed or rRefractory diffuse large B cell lymphoma

Inclusion Criteria:

Age and Disease Status
- Adult patients (age ≥ 18 years)
- with relapsed or refractory (r/r) large B-cell lymphoma, including
  - diffuse large B-cell lymphoma (DLBCL) not otherwise specified,
  - high grade B-cell lymphoma
  - and DLBCL arising from follicular lymphoma.
- Disease status:
  - after two or more lines of systemic therapy or
  - relapse after autologous HCT
Performance Status
- ECOG performance status 0-2
- ALC >/=100/uL at screening (prior to apheresis)
Organ Function
- Renal function defined as:
  - A serum creatinine of ≤1.5 x ULN OR
  - eGFR ≥ 50 mL/min/1.73 m^2
- Liver function defined as:
  - ALT ≤ 5 times the ULN for age (unless due to disease)
  - Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
- Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation SpO2 > 91% on room air
- Hemodynamically stable and LVEF ≥ 45% confirmed by echocardiogram or MUGA
- Adequate bone marrow reserve (unless marrow infiltrated by disease) defined as :
  - Absolute neutrophil count (ANC) > 1.000/mm3 (only for NHL)
  - Platelets ≥ 50.000/mm3 (transfusion support can be provided)
  - Hemoglobin >8.0 mg/dl (transfusion support can be provided)
Other Inclusion Criteria
- Life expectancy ≥12 weeks
- Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment.
- Written voluntary consent (adults) or parental/guardian consent (minors or adults with diminished capacity) prior to the performance of any research related tests or procedures.

Exclusion Criteria:

Pregnant or breastfeeding - Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
Active CNS involvement by malignancy (no evidence of disease in CSF by flow cytometry) CAR-T is not indicated for the treatment of patients with primary central nervous system lymphoma.
Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD). All GVHD medication must be stopped 2 weeks prior to apheresis.
Uncontrolled active hepatitis B or hepatitis C
Active or inactive HIV infection
Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
Unstable angina and/or myocardial infarction within 1 month prior to CAR-T infusion
Investigational medicinal product within the last 7 days prior to apheresis or CAR-T infusion
Intolerance to the excipients of the CAR-T cell product
Any immunosuppressive medication must be stopped ≥ 2 weeks prior to apheresis.
Patient has taken one of the prohibited concomitant medications within the timeframe

ARM D: Tecartus (Brexucabtagene Autoleucel) for relapsed or refractory mantle cell lymphoma

Inclusion Criteria:

Age and Disease Status

* with relapsed or refractory (r/r) mantle cell lymphoma, including
- prior anthracycline or Bendamustine containing therapy
- prior Rituximab or other CD20 directed antibody (or inability to treat with CD20 MoAb)
- not a candidate or relapse after autologous HCT
- active disease at enrollment
Performance Status

*ECOG performance status 0-1
Organ Function
- Renal function defined as:
  - A serum creatinine of ≤1.5 x ULN OR
  - eGFR ≥ 50 mL/min/1.73 m2
- Liver function defined as:
  - ALT ≤ 5 times the ULN for age (unless due to disease)
  - Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation SpO2 > 91% on room air
Hemodynamically stable and LVEF ≥ 45% confirmed by echocardiogram or MUGA
Adequate bone marrow reserve (unless marrow infiltrated by disease) defined as:
Absolute neutrophil count (ANC) > 1,000/mm^3 (only for NHL)
Platelets ≥ 50,000/mm^3 (transfusion support can be provided)
Hemoglobin >8.0 mg/dl (transfusion support can be provided)

Other Inclusion Criteria:

Life expectancy ≥12 weeks
Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment. See section 4.5 for definitions of child bearing potential and section 4.6 for definitions of adequate birth control.
Written voluntary consent (adults) or parental/guardian consent (minors or adults with diminished capacity) prior to the performance of any research related tests or procedures.

Exclusion Criteria:

Pregnant or breastfeeding - Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
Active CNS involvement by malignancy (no evidence of disease in CSF by flow cytometry) CAR-T is not indicated for the treatment of patients with primary central nervous system lymphoma.
Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD). All GVHD medication must be stopped 2 weeks prior to apheresis.
Uncontrolled active hepatitis B or hepatitis C
Active HIV infection
Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
Unstable angina and/or myocardial infarction within 1 month prior to CAR-T infusion
Investigational medicinal product within the last 7 days prior to apheresis or CAR-T infusion
Intolerance to the excipients of the CAR-T cell product
Any immunosuppressive medication must be stopped ≥ 2 weeks prior to apheresis (steroids must be stopped >72 hours prior to apheresis).
Patient has taken one of the prohibited concomitant medications within the timeframe

ARM E: Breyanzi "lisocabtagene maraleucel" for relapsed or refractory large B-cell lymphoma

Inclusion Criteria:

Age and Disease Status
- Adult patients (age ≥ 18 years)
- with relapsed or refractory disease after two or more lines of systemic therapy, including
  - diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma),
  - high-grade B-cell lymphoma,
  - primary mediastinal large B-cell lymphoma,
  - follicular lymphoma grade 3B
Performance Status

*ECOG performance status 0-2
Organ Function
- Renal function defined as:
  - A serum creatinine of ≤1.5 x ULN OR
  - eGFR ≥ 30 mL/min/1.73 m2
- Liver function defined as:
  - ALT ≤ 5 times the ULN for age (unless due to disease)
  - Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation SpO2 > 91% on room air
Hemodynamically stable and LVEF ≥ 40% confirmed by echocardiogram or MUGA
Adequate bone marrow reserve (unless marrow infiltrated by disease) defined as:
- Absolute neutrophil count (ANC) > 1,000/mm^3 (only for NHL)
- Platelets ≥ 50,000/mm^3 (transfusion support can be provided)
- Hemoglobin >8.0 mg/dl (transfusion support can be provided)

Other Inclusion Criteria:

Life expectancy ≥12 weeks
Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment. See section 4.5 for definitions of child bearing potential and section 4.6 for definitions of adequate birth control.
Written voluntary consent (adults) or parental/guardian consent (minors or adults with diminished capacity) prior to the performance of any research related tests or procedures.

Exclusion Criteria:

Pregnant or breastfeeding - Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
Active CNS involvement by malignancy (no evidence of disease in CSF by flow cytometry) CAR-T is not indicated for the treatment of patients with primary central nervous system lymphoma.
Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD). All GVHD medication must be stopped 2 weeks prior to apheresis.
Uncontrolled active hepatitis B or hepatitis C
Active HIV infection
Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
Unstable angina and/or myocardial infarction within 1 month prior to CAR-T infusion
Investigational medicinal product within the last 7 days prior to apheresis or CAR-T infusion
Intolerance to the excipients of the CAR-T cell product
Any immunosuppressive medication must be stopped ≥ 2 weeks prior to apheresis (steroids must be stopped >72 hours prior to apheresis).
Patient has taken one of the prohibited concomitant medications within the timeframe

ARM F: Abecma "Idecabtagene Vicleucel" for relapsed or refractory multiple myeloma

Inclusion Criteria:

Age and Disease Status
- Adult patients (age ≥ 18 years)
- Relapsed (progression after prior partial or complete remission) or refractory multiple myeloma
- Evidence of active disease (medullary or extramedullary)
- Prior therapy (Failure or intolerance to) with an immunomodulatory agent, a proteasome inhibitor, and an antiCD38 monoclonal antibody
Performance Status

*ECOG performance status 0-1
Organ Function
- Renal function defined as:
  - A serum creatinine of ≤2 x ULN OR
  - eGFR ≥ 50 mL/min/1.73 m2
- Liver function defined as:
  - ALT ≤ 5 times the ULN for age (unless due to disease)
  - Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation SpO2 > 91% on room air
Hemodynamically stable and LVEF ≥ 45% confirmed by echocardiogram or MUGA
Adequate bone marrow reserve (unless marrow infiltrated by disease) defined as:
- Absolute neutrophil count (ANC) > 1,000/mm^3 (only for NHL)
- Platelets ≥ 50,000/mm^3 (transfusion support can be provided)
- Hemoglobin >8.0 mg/dl (transfusion support can be provided)

Other Inclusion Criteria:

Life expectancy ≥12 weeks
Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment. See section 4.5 for definitions of child bearing potential and section 4.6 for definitions of adequate birth control.
Written voluntary consent (adults) or parental/guardian consent (minors or adults with diminished capacity) prior to the performance of any research related tests or procedures.

Exclusion Criteria:

Pregnant or breastfeeding - Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
Active CNS involvement by malignancy (no evidence of disease in CSF by flow cytometry) CAR-T is not indicated for the treatment of patients with primary central nervous system lymphoma.
Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD). All GVHD medication must be stopped 2 weeks prior to apheresis.
Uncontrolled active hepatitis B or hepatitis C
Active HIV infection
Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
Unstable angina and/or myocardial infarction within 1 month prior to CAR-T infusion
Investigational medicinal product within the last 7 days prior to apheresis or CAR-T infusion
Intolerance to the excipients of the CAR-T cell product
Any immunosuppressive medication must be stopped ≥ 2 weeks prior to apheresis (steroids must be stopped >72 hours prior to apheresis).
Patient has taken one of the prohibited concomitant medications within the timeframe

Contacts/Locations Module

Name	Affiliation	Role
Veronika Bachanova, MD, PhD	Masonic Cancer Center, University of Minnesota	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Masonic Cancer Center at University of Minnesota		Minneapolis	Minnesota	55455	United States

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	ARM A: Refractory/Relapsed B-cell Acute Lymphoblastic Leukemia (ALL)	KYMRIAH: FDA approved CD19-directed genetically modified autologous T cell immunotherapy comprised of autologous T cells Fludarabine 30mg/m2 4 doses: 30 mg/m2 IV daily for 4 doses Cyclophosphamide 500 mg/m2; 2 doses: 500 mg/m2 IV daily for 2 doses starting with the first dose of fludarabine

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Jun 30, 2023

Derived Section

Miscellaneous Info Module

Submission Tracking

Condition Browse Module

Intervention Browse Module

Masking Info

ARM C: Kymriah for Refractory diffuse large B cell lymphoma (DLBCL)

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	ARM A: Refractory/Relapsed B-cell Acute Lymphoblastic Leukemia (ALL)	KYMRIAH: FDA approved CD19-directed genetically modified autologous T cell immunotherapy comprised of autologous T cells Fludarabine 30mg/m2 4 doses: 30 mg/m2 IV daily for 4 doses Cyclophosphamide 500 mg/m2; 2 doses: 500 mg/m2 IV daily for 2 doses starting with the first dose of fludarabine
BG001	ARM B: Yescarta for Refractory Diffuse Large B Cell Lymphoma (DLBCL)	YESCARTA: CD19-directed genetically modified autologous T cell immunotherapy Fludarabine 30mg/m2 3 doses: 30 mg/m2 IV daily for 3 doses Cyclophosphamide 500 mg/m2; 3 doses: 500 mg/m2 IV daily for 3 doses starting with the first dose of fludarabine
BG002	ARM C: Kymriah for Refractory Diffuse Large B Cell Lymphoma (DLBCL)	KYMRIAH: FDA approved CD19-directed genetically modified autologous T cell immunotherapy comprised of autologous T cells Fludarabine 25mg/m2 3 days: 25 mg/m2 i.v. daily for 3 days Cyclophosphamide 250 mg/m2; 3 days: 250 mg/m2 IV daily for 3 days starting with the first dose of fludarabine
BG003	Arm D: Tecartus CAR-T Product for Mantle Cell Leukemia (MCL)	Fludarabine 30mg/m2 3 doses: 30 mg/m2 IV daily for 3 doses Cyclophosphamide 500 mg/m2; 3 doses: 500 mg/m2 IV daily for 3 doses starting with the first dose of fludarabine Tecartus: TECARTUS is a CD19-directed genetically modified autologous T cell immunotherapy, binds to CD19-expressing cancer cells and normal B cells
BG004	Arm E: Breyanzi for Relapsed or Refractory Large B-cell Lymphoma (RLBCL)	Fludarabine 30mg/m2 3 doses: 30 mg/m2 IV daily for 3 doses Cyclophosphamide 500 mg/m2; 3 doses: 500 mg/m2 IV daily for 3 doses starting with the first dose of fludarabine Breyanzi Injectable Product: Infuse BREYANZI 2 to 7 days after completion of lymphodepleting chemotherapy.
BG005	Arm F: Abecma for Relapsed or Refractory Multiple Myeloma	Fludarabine 30mg/m2 3 doses: 30 mg/m2 IV daily for 3 doses Cyclophosphamide 500 mg/m2; 3 doses: 500 mg/m2 IV daily for 3 doses starting with the first dose of fludarabine Abecma, Intravenous Suspension: Infuse ABECMA 2 days after completion of lymphodepleting chemotherapy.
BG006	Arm G: Tecartus B-cell Acute Lymphoblastic Leukemia (ALL)	Fludarabine 25mg/m2 3 days: 25 mg/m2 i.v. daily for 3 days Tecartus: TECARTUS is a CD19-directed genetically modified autologous T cell immunotherapy, binds to CD19-expressing cancer cells and normal B cells Cyclophosphamide 900 mg/m2; 1 day: Administer cyclophosphamide 900 mg/m2 over 60 minutes on the second day before infusion of TECARTUS
BG007	Total	Total of all reporting groups

Units	Counts
Participants	BG00026 BG00144 BG00230 BG0037 BG00413 BG00520 BG00610 BG007150

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG00017 BG0010 BG0020 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0006 BG00115 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0001 BG0010 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG00026 BG00144 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Arms B & C&D& E&F: Overall Response Rate (ORR)

ORR defined by complete response + partial response by Lugano

Posted

Number

95% Confidence Interval

Percentage of participants

Day 100

ID	Title	Description
OG000	ARM B: Yescarta for Refractory Diffuse Large B Cell Lymphoma (DLBCL)	YESCARTA: CD19-directed genetically modified autologous T cell immunotherapy Fludarabine 30mg/m2 3 doses: 30 mg/m2 IV daily for 3 doses Cyclophosphamide 500 mg/m2; 3 doses: 500 mg/m2 IV daily for 3 doses starting with the first dose of fludarabine
OG001	ARM C: Kymriah for Refractory Diffuse Large B Cell Lymphoma (DLBCL)	KYMRIAH: FDA approved CD19-directed genetically modified autologous T cell immunotherapy comprised of autologous T cells Fludarabine 25mg/m2 3 days: 25 mg/m2 i.v. daily for 3 days Cyclophosphamide 250 mg/m2; 3 days: 250 mg/m2 IV daily for 3 days starting with the first dose of fludarabine
OG002	Arm D: Tecartus CAR-T Product for Mantle Cell Leukemia (MCL)	Fludarabine 30mg/m2 3 doses: 30 mg/m2 IV daily for 3 doses Cyclophosphamide 500 mg/m2; 3 doses: 500 mg/m2 IV daily for 3 doses starting with the first dose of fludarabine Tecartus: TECARTUS is a CD19-directed genetically modified autologous T cell immunotherapy, binds to CD19-expressing cancer cells and normal B cells
OG003	Arm E: Breyanzi for Relapsed or Refractory Large B-cell Lymphoma (RLBCL)	Fludarabine 30mg/m2 3 doses: 30 mg/m2 IV daily for 3 doses Cyclophosphamide 500 mg/m2; 3 doses: 500 mg/m2 IV daily for 3 doses starting with the first dose of fludarabine Breyanzi Injectable Product: Infuse BREYANZI 2 to 7 days after completion of lymphodepleting chemotherapy.
OG004	Arm F: Abecma for Relapsed or Refractory Multiple Myeloma	Fludarabine 30mg/m2 3 doses: 30 mg/m2 IV daily for 3 doses Cyclophosphamide 500 mg/m2; 3 doses: 500 mg/m2 IV daily for 3 doses starting with the first dose of fludarabine Abecma, Intravenous Suspension: Infuse ABECMA 2 days after completion of lymphodepleting chemotherapy.

Units	Counts
Participants	OG00044 OG00130 OG0027 OG003

Title

Denominators

Categories

Title	Measurements
	OG00077.3(63 to 87.2) OG00161.3(43.8 to 76.3) OG002100(59 to 100) OG003

Primary

Arm A & E: MRD-negative CR (or CRi)

Percentage of patients with MRD-negative Complete Response CR (or CRi)

Posted

Number

95% Confidence Interval

Percentage of participants

Day 28

ID	Title	Description
OG000	ARM A: Refractory/Relapsed B-cell Acute Lymphoblastic Leukemia (ALL)	KYMRIAH: FDA approved CD19-directed genetically modified autologous T cell immunotherapy comprised of autologous T cells Fludarabine 30mg/m2 4 doses: 30 mg/m2 IV daily for 4 doses Cyclophosphamide 500 mg/m2; 2 doses: 500 mg/m2 IV daily for 2 doses starting with the first dose of fludarabine
OG001	Arm E: Breyanzi for Relapsed or Refractory Large B-cell Lymphoma (RLBCL)	Fludarabine 30mg/m2 3 doses: 30 mg/m2 IV daily for 3 doses Cyclophosphamide 500 mg/m2; 3 doses: 500 mg/m2 IV daily for 3 doses starting with the first dose of fludarabine Breyanzi Injectable Product: Infuse BREYANZI 2 to 7 days after completion of lymphodepleting chemotherapy.

Units	Counts
Participants	OG000

Secondary

Percentage of Patients Developing Grade 3 or 4 ICANS

Percentage of patients developing grade 3 or 4 ICANS

Posted

Number

95% Confidence Interval

Percentage of participants

Day 28

ID	Title	Description
OG000	ARM A: Refractory/Relapsed B-cell Acute Lymphoblastic Leukemia (ALL)	KYMRIAH: FDA approved CD19-directed genetically modified autologous T cell immunotherapy comprised of autologous T cells Fludarabine 30mg/m2 4 doses: 30 mg/m2 IV daily for 4 doses Cyclophosphamide 500 mg/m2; 2 doses: 500 mg/m2 IV daily for 2 doses starting with the first dose of fludarabine
OG001	ARM B: Yescarta for Refractory Diffuse Large B Cell Lymphoma (DLBCL)	YESCARTA: CD19-directed genetically modified autologous T cell immunotherapy Fludarabine 30mg/m2 3 doses: 30 mg/m2 IV daily for 3 doses Cyclophosphamide 500 mg/m2; 3 doses: 500 mg/m2 IV daily for 3 doses starting with the first dose of fludarabine
OG002	ARM C: Kymriah for Refractory Diffuse Large B Cell Lymphoma (DLBCL)	KYMRIAH: FDA approved CD19-directed genetically modified autologous T cell immunotherapy comprised of autologous T cells Fludarabine 25mg/m2 3 days: 25 mg/m2 i.v. daily for 3 days Cyclophosphamide 250 mg/m2; 3 days: 250 mg/m2 IV daily for 3 days starting with the first dose of fludarabine

Secondary

Treatment Related Mortality (TRM)

Incidence of treatment related mortality (in absence of disease relapse/progression)

Posted

Number

95% Confidence Interval

Percentage of participants

Day 28

ID	Title	Description
OG000	ARM A: Refractory/Relapsed B-cell Acute Lymphoblastic Leukemia (ALL)	KYMRIAH: FDA approved CD19-directed genetically modified autologous T cell immunotherapy comprised of autologous T cells Fludarabine 30mg/m2 4 doses: 30 mg/m2 IV daily for 4 doses Cyclophosphamide 500 mg/m2; 2 doses: 500 mg/m2 IV daily for 2 doses starting with the first dose of fludarabine
OG001	ARM B: Yescarta for Refractory Diffuse Large B Cell Lymphoma (DLBCL)	YESCARTA: CD19-directed genetically modified autologous T cell immunotherapy Fludarabine 30mg/m2 3 doses: 30 mg/m2 IV daily for 3 doses Cyclophosphamide 500 mg/m2; 3 doses: 500 mg/m2 IV daily for 3 doses starting with the first dose of fludarabine
OG002	ARM C: Kymriah for Refractory Diffuse Large B Cell Lymphoma (DLBCL)	KYMRIAH: FDA approved CD19-directed genetically modified autologous T cell immunotherapy comprised of autologous T cells Fludarabine 25mg/m2 3 days: 25 mg/m2 i.v. daily for 3 days Cyclophosphamide 250 mg/m2; 3 days: 250 mg/m2 IV daily for 3 days starting with the first dose of fludarabine

Secondary

Treatment Related Mortality (TRM)

Incidence of treatment related mortality (in absence of disease relapse/progression)

Posted

Number

95% Confidence Interval

Percentage of participants

Day 100

ID	Title	Description
OG000	ARM A: Refractory/Relapsed B-cell Acute Lymphoblastic Leukemia (ALL)	KYMRIAH: FDA approved CD19-directed genetically modified autologous T cell immunotherapy comprised of autologous T cells Fludarabine 30mg/m2 4 doses: 30 mg/m2 IV daily for 4 doses Cyclophosphamide 500 mg/m2; 2 doses: 500 mg/m2 IV daily for 2 doses starting with the first dose of fludarabine
OG001	ARM B: Yescarta for Refractory Diffuse Large B Cell Lymphoma (DLBCL)	YESCARTA: CD19-directed genetically modified autologous T cell immunotherapy Fludarabine 30mg/m2 3 doses: 30 mg/m2 IV daily for 3 doses Cyclophosphamide 500 mg/m2; 3 doses: 500 mg/m2 IV daily for 3 doses starting with the first dose of fludarabine
OG002	ARM C: Kymriah for Refractory Diffuse Large B Cell Lymphoma (DLBCL)	KYMRIAH: FDA approved CD19-directed genetically modified autologous T cell immunotherapy comprised of autologous T cells Fludarabine 25mg/m2 3 days: 25 mg/m2 i.v. daily for 3 days Cyclophosphamide 250 mg/m2; 3 days: 250 mg/m2 IV daily for 3 days starting with the first dose of fludarabine

Secondary

Treatment Related Mortality (TRM)

Incidence of treatment related mortality (in absence of disease relapse/progression)

Posted

Number

95% Confidence Interval

Percentage of participants

1 Year

ID	Title	Description
OG000	ARM A: Refractory/Relapsed B-cell Acute Lymphoblastic Leukemia (ALL)	KYMRIAH: FDA approved CD19-directed genetically modified autologous T cell immunotherapy comprised of autologous T cells Fludarabine 30mg/m2 4 doses: 30 mg/m2 IV daily for 4 doses Cyclophosphamide 500 mg/m2; 2 doses: 500 mg/m2 IV daily for 2 doses starting with the first dose of fludarabine
OG001	ARM B: Yescarta for Refractory Diffuse Large B Cell Lymphoma (DLBCL)	YESCARTA: CD19-directed genetically modified autologous T cell immunotherapy Fludarabine 30mg/m2 3 doses: 30 mg/m2 IV daily for 3 doses Cyclophosphamide 500 mg/m2; 3 doses: 500 mg/m2 IV daily for 3 doses starting with the first dose of fludarabine
OG002	ARM C: Kymriah for Refractory Diffuse Large B Cell Lymphoma (DLBCL)	KYMRIAH: FDA approved CD19-directed genetically modified autologous T cell immunotherapy comprised of autologous T cells Fludarabine 25mg/m2 3 days: 25 mg/m2 i.v. daily for 3 days Cyclophosphamide 250 mg/m2; 3 days: 250 mg/m2 IV daily for 3 days starting with the first dose of fludarabine

Secondary

Relapse-free Survival (RFS)

Incidence of Relapse-free Survival (RFS)

Posted

Number

95% Confidence Interval

Percentage of participants

1 year

ID	Title	Description
OG000	ARM A: Refractory/Relapsed B-cell Acute Lymphoblastic Leukemia (ALL)	KYMRIAH: FDA approved CD19-directed genetically modified autologous T cell immunotherapy comprised of autologous T cells Fludarabine 30mg/m2 4 doses: 30 mg/m2 IV daily for 4 doses Cyclophosphamide 500 mg/m2; 2 doses: 500 mg/m2 IV daily for 2 doses starting with the first dose of fludarabine
OG001	ARM B: Yescarta for Refractory Diffuse Large B Cell Lymphoma (DLBCL)	YESCARTA: CD19-directed genetically modified autologous T cell immunotherapy Fludarabine 30mg/m2 3 doses: 30 mg/m2 IV daily for 3 doses Cyclophosphamide 500 mg/m2; 3 doses: 500 mg/m2 IV daily for 3 doses starting with the first dose of fludarabine
OG002	ARM C: Kymriah for Refractory Diffuse Large B Cell Lymphoma (DLBCL)	KYMRIAH: FDA approved CD19-directed genetically modified autologous T cell immunotherapy comprised of autologous T cells Fludarabine 25mg/m2 3 days: 25 mg/m2 i.v. daily for 3 days Cyclophosphamide 250 mg/m2; 3 days: 250 mg/m2 IV daily for 3 days starting with the first dose of fludarabine

Secondary

Event-Free Survival (EFS)

Incidence of event-free survival (EFS) from the date of the CAR-T infusion through 1 year post treatment

Not Posted

1 Year post treatment

Participants

Secondary

Overall Survival (OS)

Incidence of Overall Survival (OS) from the date of the CAR-T infusion through the date of patient death for any reason.

Posted

Number

95% Confidence Interval

Percentage of participants

1 year

ID	Title	Description
OG000	ARM A: Refractory/Relapsed B-cell Acute Lymphoblastic Leukemia (ALL)	KYMRIAH: FDA approved CD19-directed genetically modified autologous T cell immunotherapy comprised of autologous T cells Fludarabine 30mg/m2 4 doses: 30 mg/m2 IV daily for 4 doses Cyclophosphamide 500 mg/m2; 2 doses: 500 mg/m2 IV daily for 2 doses starting with the first dose of fludarabine
OG001	ARM B: Yescarta for Refractory Diffuse Large B Cell Lymphoma (DLBCL)	YESCARTA: CD19-directed genetically modified autologous T cell immunotherapy Fludarabine 30mg/m2 3 doses: 30 mg/m2 IV daily for 3 doses Cyclophosphamide 500 mg/m2; 3 doses: 500 mg/m2 IV daily for 3 doses starting with the first dose of fludarabine
OG002	ARM C: Kymriah for Refractory Diffuse Large B Cell Lymphoma (DLBCL)	KYMRIAH: FDA approved CD19-directed genetically modified autologous T cell immunotherapy comprised of autologous T cells Fludarabine 25mg/m2 3 days: 25 mg/m2 i.v. daily for 3 days Cyclophosphamide 250 mg/m2; 3 days: 250 mg/m2 IV daily for 3 days starting with the first dose of fludarabine

Secondary

Overall Toxicity

Percentage of patients with grade 3 or 4 targeted toxicity of CRS and/or neurotoxicity

Posted

Number

95% Confidence Interval

Percentage of participants

Day 28

ID	Title	Description
OG000	ARM A: Refractory/Relapsed B-cell Acute Lymphoblastic Leukemia (ALL)	KYMRIAH: FDA approved CD19-directed genetically modified autologous T cell immunotherapy comprised of autologous T cells Fludarabine 30mg/m2 4 doses: 30 mg/m2 IV daily for 4 doses Cyclophosphamide 500 mg/m2; 2 doses: 500 mg/m2 IV daily for 2 doses starting with the first dose of fludarabine
OG001	ARM B: Yescarta for Refractory Diffuse Large B Cell Lymphoma (DLBCL)	YESCARTA: CD19-directed genetically modified autologous T cell immunotherapy Fludarabine 30mg/m2 3 doses: 30 mg/m2 IV daily for 3 doses Cyclophosphamide 500 mg/m2; 3 doses: 500 mg/m2 IV daily for 3 doses starting with the first dose of fludarabine
OG002	ARM C: Kymriah for Refractory Diffuse Large B Cell Lymphoma (DLBCL)	KYMRIAH: FDA approved CD19-directed genetically modified autologous T cell immunotherapy comprised of autologous T cells Fludarabine 25mg/m2 3 days: 25 mg/m2 i.v. daily for 3 days Cyclophosphamide 250 mg/m2; 3 days: 250 mg/m2 IV daily for 3 days starting with the first dose of fludarabine

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (At Risk)
EG000	ARM A: Refractory/Relapsed B-cell Acute Lymphoblastic Leukemia (ALL)	KYMRIAH: FDA approved CD19-directed genetically modified autologous T cell immunotherapy comprised of autologous T cells Fludarabine 30mg/m2 4 doses: 30 mg/m2 IV daily for 4 doses Cyclophosphamide 500 mg/m2; 2 doses: 500 mg/m2 IV daily for 2 doses starting with the first dose of fludarabine	0	26	0	26	26
EG001	ARM B: Yescarta for Refractory Diffuse Large B Cell Lymphoma (DLBCL)	YESCARTA: CD19-directed genetically modified autologous T cell immunotherapy Fludarabine 30mg/m2 3 doses: 30 mg/m2 IV daily for 3 doses Cyclophosphamide 500 mg/m2; 3 doses: 500 mg/m2 IV daily for 3 doses starting with the first dose of fludarabine	3	44	1	44	44
EG002	ARM C: Kymriah for Refractory Diffuse Large B Cell Lymphoma (DLBCL)	KYMRIAH: FDA approved CD19-directed genetically modified autologous T cell immunotherapy comprised of autologous T cells Fludarabine 25mg/m2 3 days: 25 mg/m2 i.v. daily for 3 days Cyclophosphamide 250 mg/m2; 3 days: 250 mg/m2 IV daily for 3 days starting with the first dose of fludarabine	0	30	0	30	30
EG003	Arm D: Tecartus CAR-T Product for Mantle Cell Leukemia (MCL)	Fludarabine 30mg/m2 3 doses: 30 mg/m2 IV daily for 3 doses Cyclophosphamide 500 mg/m2; 3 doses: 500 mg/m2 IV daily for 3 doses starting with the first dose of fludarabine Tecartus: TECARTUS is a CD19-directed genetically modified autologous T cell immunotherapy, binds to CD19-expressing cancer cells and normal B cells	1	7	0	7	7
EG004	Arm E: Breyanzi for Relapsed or Refractory Large B-cell Lymphoma (RLBCL)	Fludarabine 30mg/m2 3 doses: 30 mg/m2 IV daily for 3 doses Cyclophosphamide 500 mg/m2; 3 doses: 500 mg/m2 IV daily for 3 doses starting with the first dose of fludarabine Breyanzi Injectable Product: Infuse BREYANZI 2 to 7 days after completion of lymphodepleting chemotherapy.	2	13	0	13	13
EG005	Arm F: Abecma for Relapsed or Refractory Multiple Myeloma	Fludarabine 30mg/m2 3 doses: 30 mg/m2 IV daily for 3 doses Cyclophosphamide 500 mg/m2; 3 doses: 500 mg/m2 IV daily for 3 doses starting with the first dose of fludarabine Abecma, Intravenous Suspension: Infuse ABECMA 2 days after completion of lymphodepleting chemotherapy.	0	20	0	20	20
EG006	Arm G: Tecartus B-cell Acute Lymphoblastic Leukemia (ALL)	Fludarabine 25mg/m2 3 days: 25 mg/m2 i.v. daily for 3 days Tecartus: TECARTUS is a CD19-directed genetically modified autologous T cell immunotherapy, binds to CD19-expressing cancer cells and normal B cells Cyclophosphamide 900 mg/m2; 1 day: Administer cyclophosphamide 900 mg/m2 over 60 minutes on the second day before infusion of TECARTUS	0	10	0	10	10

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Adult respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders		Systematic Assessment		EG0000 events0 affected26 at risk EG0011 events1 affected44 at risk EG0020 events0 affected30 at risk EG0030 events0 affected7 at risk EG004

First MCP Posted Date

ID	Term
D054198	Precursor Cell Lymphoblastic Leukemia-Lymphoma

Ancestor Terms

ID	Term
D007945	Leukemia, Lymphoid
D007938	Leukemia
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases

ID	Term
C000626284	tisagenlecleucel
C000629083	axicabtagene ciloleucel
C024352	fludarabine
D003520	Cyclophosphamide
C000705347	brexucabtagene autoleucel

Ancestor Terms

ID	Term
D010752	Phosphoramide Mustards
D009588	Nitrogen Mustard Compounds
D009150	Mustard Compounds
D006846	Hydrocarbons, Halogenated
D006838	Hydrocarbons
D009930	Organic Chemicals
D063088	Phosphoramides
D009943	Organophosphorus Compounds

OG00435(18.1 to 56.7)

EG0050 events0 affected20 at risk

EG0060 events0 affected10 at risk