Clinical Trials /

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

NCT03642626

Description:

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.

Related Conditions:
  • B-Cell Acute Lymphoblastic Leukemia
  • Diffuse Large B-Cell Lymphoma
  • Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
  • High Grade B-Cell Lymphoma, Not Otherwise Specified
  • Mediastinal Large B-Cell Lymphoma
Recruiting Status:

Recruiting

Trial Eligibility

Document

Title

  • Brief Title: MT2017-45: CAR-T Cell Therapy for Heme Malignancies
  • Official Title: Chimeric Antigen Receptor (CAR)-T Cell Therapy for Patients With Hematologic Malignancies

Clinical Trial IDs

  • ORG STUDY ID: 2017LS118
  • SECONDARY ID: MT2017-45
  • NCT ID: NCT03642626

Conditions

  • Acute Lymphoblastic Leukemia
  • Large B-cell Lymphoma

Interventions

DrugSynonymsArms
KYMRIAHtisagenlecleucelARM A: Refractory/relapsed B-cell acute lymphoblastic leuk
YESCARTAARM B: Yescarta for Refractory diffuse large B cell lymphom
FludarabineARM A: Refractory/relapsed B-cell acute lymphoblastic leuk
CyclophosphamideARM A: Refractory/relapsed B-cell acute lymphoblastic leuk
FludarabineARM B: Yescarta for Refractory diffuse large B cell lymphom
CyclophosphamideARM B: Yescarta for Refractory diffuse large B cell lymphom
FludarabineARM C: Kymriah for Refractory diffuse large B cell lymphom
CyclophosphamideARM C: Kymriah for Refractory diffuse large B cell lymphom

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
ARM A: Refractory/relapsed B-cell acute lymphoblastic leuk
  • KYMRIAH
  • Fludarabine
  • Cyclophosphamide
ARM B: Yescarta for Refractory diffuse large B cell lymphom
  • YESCARTA
  • Fludarabine
  • Cyclophosphamide
ARM C: Kymriah for Refractory diffuse large B cell lymphom
  • KYMRIAH
  • Fludarabine
  • Cyclophosphamide

Eligibility Criteria

        ARM A: Kymriah for Refractory/relapsed B-cell acute lymphoblastic leukemia expressing CD19

          -  Age and Disease Status

               -  Must be age 0-25 years

               -  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

               -  Karnofsky (age ≥16 years) or Lansky (age < 16 years) performance status ≥ 50% at
                  screening

               -  ALC >500/uL at screening (prior to apheresis) and absolute lymphocyte count >/=
                  150/uL

          -  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

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Arm A: Complete Remission (CR)
Time Frame:Day 28
Safety Issue:
Description:Incidence of CR

Secondary Outcome Measures

Measure:Arm A: MRD-negative CR (or CRi)
Time Frame:Day 28
Safety Issue:
Description:Proportion of patients with MRD-negative CR (or CRi)
Measure:Arm A: Proportion of patients who are alive but not in remission
Time Frame:Day 28
Safety Issue:
Description:Proportion of patients who are alive but not in remission
Measure:Arm A: Treatment Related Mortality (TRM)
Time Frame:Day 28
Safety Issue:
Description:Incidence of treatment related mortality (in absence of disease relapse/progression)
Measure:Arm A: Treatment Related Mortality (TRM)
Time Frame:Day 100
Safety Issue:
Description:Incidence of treatment related mortality (in absence of disease relapse/progression)
Measure:Arm A: Treatment Related Mortality (TRM)
Time Frame:1 Year
Safety Issue:
Description:Incidence of treatment related mortality (in absence of disease relapse/progression)
Measure:Arm A: Relapse-free Survival (RFS)
Time Frame:At complete remission, relapse, death
Safety Issue:
Description:Incidence of Relapse-free Survival (RFS)
Measure:Arm A: Event-Free Survival (EFS)
Time Frame:1 Year post treatment
Safety Issue:
Description:Incidence of event-free survival (EFS) from the date of the CAR-T infusion through 1 year post treatment
Measure:Arm A: Overall Survival (OS)
Time Frame:Date of Death
Safety Issue:
Description:Incidence of Overall Survival (OS) from the date of the CAR-T infusion through the date of patient death for any reason.
Measure:Arm A: Toxicity
Time Frame:Day 28
Safety Issue:
Description:Proportion of patients with grade 3 or 4 targeted toxicity of CRS and/or neurotoxicity
Measure:Arms B/C: Complete Remission (CR)
Time Frame:Day 28
Safety Issue:
Description:Proportion of patients with Complete Remission by Lugano criteria
Measure:Arms B/C: Treatment Related Mortality (TRM)
Time Frame:Day 28
Safety Issue:
Description:Incidence of treatment related mortality
Measure:Arms B/C: Treatment Related Mortality (TRM)
Time Frame:Day 100
Safety Issue:
Description:Incidence of treatment related mortality
Measure:Arms B/C: Treatment Related Mortality (TRM)
Time Frame:1 Year
Safety Issue:
Description:Incidence of treatment related mortality
Measure:Arms B/C: Relapse-free Survival (RFS)
Time Frame:At complete remission, relapse, or death
Safety Issue:
Description:Incidence of Relapse-free Survival (RFS)
Measure:Arms B/C: Event-free Survival (EFS)
Time Frame:1 Year post treatment
Safety Issue:
Description:Event-free survival (EFS) from the date of the CAR-T infusion through 1 year post treatment
Measure:Arms B/C: Overall Survival (OS)
Time Frame:Date of Death
Safety Issue:
Description:Incidence of Overall Survival (OS) from the date of the CAR-T infusion through the date of patient death for any reason
Measure:Arms B/C: Toxicity
Time Frame:Day 28
Safety Issue:
Description:Proportion of patients developing grade 3, 4 targeted toxicity of CRS and/or neurotoxicity

Details

Phase:
Primary Purpose:Observational
Overall Status:Recruiting
Lead Sponsor:Masonic Cancer Center, University of Minnesota

Trial Keywords

  • ALL
  • CAR-T
  • CAR19-T
  • chimeric antigen receptor T cells

Last Updated

March 8, 2021