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

Chimeric Antigen Receptor (CAR)-T Cell Therapy for Patients With Hematologic Malignancies

This is a phase II study of FDA-approved CAR-T products for patients with hematologic malignancies. Patients will be assigned to Arm A and B based on age and diagnosis. Overall remission rate, safety events and other endpoints will be calculated for Arm A and B separately.

Study Overview

• Status: Active, not recruiting
• Conditions: Acute Lymphoblastic Leukemia; Large B-cell Lymphoma
• Intervention / Treatment: Drug: KYMRIAH; Drug: Fludarabine 30mg/m2 4 doses; Drug: Cyclophosphamide 500 mg/m2; 2 doses; Drug: YESCARTA; Drug: Fludarabine 30mg/m2 3 doses; Drug: Cyclophosphamide 500 mg/m2; 3 doses; Drug: Fludarabine 25mg/m2 3 days; Drug: Cyclophosphamide 250 mg/m2; 3 days; Drug: Tecartus; Drug: Breyanzi Injectable Product; Drug: Abecma, Intravenous Suspension; Drug: Cyclophosphamide 900 mg/m2; 1 day

• Study Type: Observational
• Enrollment (Actual): 144

Contacts and Locations

• Study Contact: Name: Tamy Grainger, RN; Phone Number: 612-273-2800; Email: tgraing1@fairview.org
• Study Contact Backup: Name: Carol Rose; Phone Number: 612-273-2800; Email: crose1@faireview.org

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Masonic Cancer Center at University of Minnesota

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Study entry is open to patients 0 through 75 years of age with hematologic malignancies.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

7

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
ARM A: Refractory/relapsed B-cell acute lymphoblastic leukemia (ALL)	Drug: KYMRIAH; FDA approved CD19-directed genetically modified autologous T cell immunotherapy comprised of autologous T cells; Other Names: tisagenlecleucel; Drug: Fludarabine 30mg/m2 4 doses; 30 mg/m2 IV daily for 4 doses; Drug: Cyclophosphamide 500 mg/m2; 2 doses; 500 mg/m2 IV daily for 2 doses starting with the first dose of fludarabine
ARM B: Yescarta for Refractory diffuse large B cell lymphoma (DLBCL)	Drug: YESCARTA; CD19-directed genetically modified autologous T cell immunotherapy; Drug: Fludarabine 30mg/m2 3 doses; 30 mg/m2 IV daily for 3 doses; Drug: Cyclophosphamide 500 mg/m2; 3 doses; 500 mg/m2 IV daily for 3 doses starting with the first dose of fludarabine
ARM C: Kymriah for Refractory diffuse large B cell lymphoma (DLBCL)	Drug: KYMRIAH; FDA approved CD19-directed genetically modified autologous T cell immunotherapy comprised of autologous T cells; Other Names: tisagenlecleucel; Drug: Fludarabine 25mg/m2 3 days; 25 mg/m2 i.v. daily for 3 days; Drug: Cyclophosphamide 250 mg/m2; 3 days; 250 mg/m2 IV daily for 3 days starting with the first dose of fludarabine
Arm D: Tecartus CAR-T product for Mantle Cell Leukemia (MCL)	Drug: Fludarabine 30mg/m2 3 doses; 30 mg/m2 IV daily for 3 doses; Drug: Cyclophosphamide 500 mg/m2; 3 doses; 500 mg/m2 IV daily for 3 doses starting with the first dose of fludarabine; Drug: Tecartus; TECARTUS is a CD19-directed genetically modified autologous T cell immunotherapy, binds to CD19-expressing cancer cells and normal B cells; Other Names: Brexucabtagene Autoleucel
Arm E: Breyanzi for relapsed or refractory large B-cell lymphoma (RLBCL)	Drug: Fludarabine 30mg/m2 3 doses; 30 mg/m2 IV daily for 3 doses; Drug: Cyclophosphamide 500 mg/m2; 3 doses; 500 mg/m2 IV daily for 3 doses starting with the first dose of fludarabine; Drug: Breyanzi Injectable Product; Infuse BREYANZI 2 to 7 days after completion of lymphodepleting chemotherapy.
Arm F: Abecma for relapsed or refractory multiple myeloma	Drug: Fludarabine 30mg/m2 3 doses; 30 mg/m2 IV daily for 3 doses; Drug: Cyclophosphamide 500 mg/m2; 3 doses; 500 mg/m2 IV daily for 3 doses starting with the first dose of fludarabine; Drug: Abecma, Intravenous Suspension; Infuse ABECMA 2 days after completion of lymphodepleting chemotherapy.
Arm G: Tecartus B-cell acute lymphoblastic leukemia (ALL)	Drug: Fludarabine 25mg/m2 3 days; 25 mg/m2 i.v. daily for 3 days; Drug: Tecartus; TECARTUS is a CD19-directed genetically modified autologous T cell immunotherapy, binds to CD19-expressing cancer cells and normal B cells; Other Names: Brexucabtagene Autoleucel; Drug: Cyclophosphamide 900 mg/m2; 1 day; Administer cyclophosphamide 900 mg/m2 over 60 minutes on the second day before infusion of TECARTUS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arm A&G: Complete Remission (CR)	Incidence of CR	Day 28
Arm A&G: CRi (complete remission without count recovery)	Incidence of CRi	Day 28
Arms B & C&D& E&F: Overall Response Rate (ORR)	ORR defined by complete response + partial response by Lugano	Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arm A: MRD-negative CR (or CRi)	Proportion of patients with MRD-negative CR (or CRi)	Day 28
Arm A: Proportion of patients who are alive but not in remission	Proportion of patients who are alive but not in remission	Day 28
Treatment Related Mortality (TRM)	Incidence of treatment related mortality (in absence of disease relapse/progression)	Day 28
Treatment Related Mortality (TRM)	Incidence of treatment related mortality (in absence of disease relapse/progression)	Day 100
Treatment Related Mortality (TRM)	Incidence of treatment related mortality (in absence of disease relapse/progression)	1 Year
Relapse-free Survival (RFS)	Incidence of Relapse-free Survival (RFS)	At complete remission to relapse or death
Event-Free Survival (EFS)	Incidence of event-free survival (EFS) from the date of the CAR-T infusion through 1 year post treatment	1 Year post treatment
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.	Date of Death
Toxicity	Proportion of patients with grade 3 or 4 targeted toxicity of CRS and/or neurotoxicity	Day 28

Collaborators and Investigators

• Sponsor: Masonic Cancer Center, University of Minnesota
• Investigators: Principal Investigator: Veronika Bachanova, MD, PhD, Masonic Cancer Center, University of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2018
• Primary Completion (Actual): February 9, 2024
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: August 21, 2018
• First Submitted That Met QC Criteria: August 21, 2018
• First Posted (Actual): August 22, 2018

Study Record Updates

• Last Update Posted (Actual): March 18, 2024
• Last Update Submitted That Met QC Criteria: March 15, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: CAR-T; ALL; CAR19-T; chimeric antigen receptor T cells
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Hematologic Diseases; Leukemia, Lymphoid; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Immunological; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Vidarabine; Axicabtagene ciloleucel; Brexucabtagene autoleucel; Tisagenlecleucel
• Other Study ID Numbers: 2017LS118; MT2017-45 (Other Identifier: University of Minnesota Masonic Cancer Center); NCI-2020-04527 (Registry Identifier: CTRP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No