Clinical Trials /

A Phase I Trial of Donor- Derived 19-28z CAR T Cells Following Allogeneic Transplant for the Treatment of CD19 Malignancies

NCT04556266

Description:

The purposed of this study is to determine whether an infusion with specialized 'modified T cells' (or CD19 chimeric antigen T cells, also called CD19 CAR T cells) that target the B cell marker will reduce the risk of relapse after transplant.

Related Conditions:
  • Acute Lymphoblastic Leukemia
  • B-Cell Non-Hodgkin Lymphoma
  • Chronic Lymphocytic Leukemia
  • Richter Syndrome
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Phase I Trial of Donor- Derived 19-28z CAR T Cells Following Allogeneic Transplant for the Treatment of CD19 Malignancies
  • Official Title: A Phase I Trial Evaluating the Safety of Consolidative Infusions of CD19-Specific Chimeric Antigen Receptor (CAR) T Cells Following T-cell Depleted Allogeneic Transplantation for High Risk B-cell Malignancies

Clinical Trial IDs

  • ORG STUDY ID: 17-331
  • NCT ID: NCT04556266

Conditions

  • Leukemia
  • Lymphoma
  • Lymphoma, B-Cell

Interventions

DrugSynonymsArms
CAR T-Cell InfusionCohort -1

Purpose

The purposed of this study is to determine whether an infusion with specialized 'modified T cells' (or CD19 chimeric antigen T cells, also called CD19 CAR T cells) that target the B cell marker will reduce the risk of relapse after transplant.

Trial Arms

NameTypeDescriptionInterventions
Cohort -1ExperimentalCohorts of 3-6 patients each will be treated with escalating doses of consolidative modified T cells at Day 30 (+/- 5 days) post allo-HSCT Total T-Cell Dose: 1 x 10^4 cells/kg
  • CAR T-Cell Infusion
Cohort 1ExperimentalCohorts of 3-6 patients each will be treated with escalating doses of consolidative modified T cells at Day 30 (+/- 5 days) post allo-HSCT Total T-Cell Dose: 1 x 10^5 cells/kg
  • CAR T-Cell Infusion
Cohort IIExperimentalCohorts of 3-6 patients each will be treated with escalating doses of consolidative modified T cells at Day 30 (+/- 5 days) post allo-HSCT Total T-Cell Dose: 2 x 10^5 cells/kg
  • CAR T-Cell Infusion
Cohort IIIExperimentalCohorts of 3-6 patients each will be treated with escalating doses of consolidative modified T cells at Day 30 (+/- 5 days) post allo-HSCT Total T-Cell Dose: 4 x 10^5 cells/kg
  • CAR T-Cell Infusion

Eligibility Criteria

        Inclusion Criteria:

        The following criteria must be met prior to the allogenic transplantation:

          1. ALL in second remission or greater (≥ CR2)

               -  Please refer to section 3.0 for more discussion of ALL in CR1 versus CR2

          2. CLL

               1. High risk in any remission status as defined by 17p deletion or Richter's
                  transformation, or

               2. All other patients eligible after at least 2 lines of standard or investigational
                  chemotherapy

          3. B-NHL

               1. Refractory or stable disease to last line of therapy per ICML 2014. Patients
                  should have at least 2 lines of prior therapy.

               2. Relapsed disease in patients who are not candidates for autologous transplant

          4. Patient's age is ≥ 18 and ≤ 60.

          5. KPS ≥ 70%

          6. Patients must have CD19 expression (by any detection method) demonstrated on their
             malignant cells at the time of enrollment on the protocol.

          7. Patients relapsed after prior CD19 CAR T cell or blinatumomab are eligible for
             enrollment as long as CD19 expression is still prese on the malignant cells.

          8. Patients who have a matched related donor willing to donate HSC for allograft and PBMC
             for CAR T cell generation

          9. Patients must have adequate organ function measured by:

               1. Cardiac: asymptomatic or if symptomatic then LVEF at rest must be > 50%

               2. Hepatic: < 3x ULN ALT and < 1.5 total serum bilirubin, unless there is congenital
                  benign hyperbilirubinemia.

               3. Renal: serum creatinine <1.3 mg/dl or if serum creatinine is outside the normal
                  range, then CrCl > 60 ml/min (measured or calculated/estimated)

               4. Pulmonary: asymptomatic or if symptomatic, DLCO > 50% of predicted (corrected for
                  hemoglobin)

               5. Negative serum pregnancy test for women of child-bearing potential is required

        Exclusion Criteria:

          1. Active and uncontrolled infection at time of transplantation. Please note that
             patients being actively treated for a viral reactivation may be enrolled on the
             protocol at the discretion of the investigators.

          2. Patients who have undergone a prior allogeneic or autologous stem cell transplant
             within the previous six months.

          3. Pregnant or breast feeding

          4. HIV infection

          5. Progressive disease at time of transplant

          6. Patients with known autoimmune disease.

          7. Patients with active or clinically significant neurological disorders, such as seizure
             disorders.
      
Maximum Eligible Age:60 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose (MTD)
Time Frame:24 month
Safety Issue:
Description:To determine maximum tolerated dose (MTD) of intravenously administered allogeneic, donor-derived 19-28z CAR T cells administered following TCD allo-HSCT for patients with high-risk CD19+ malignancies

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Leukemia
  • Lymphoma
  • Lymphoma, B-Cell
  • Chimeric Antigen Receptor (CAR) T cells
  • CART cells
  • high-risk B-cell malignancies
  • 17-331
  • Memorial Sloan Kettering Cancer Center

Last Updated

September 15, 2020