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

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase: Withdrawn; Phase 1

Conditions: Lymphoma, B-Cell; Lymphoma; Leukemia

Treatments: Biological: CAR T-Cell Infusion

Study type: Interventional

Funder types: Other

Identifiers

NCT04556266

17-331

Details and patient eligibility

About

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.

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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0 participants in 4 patient groups

Cohort -1

Experimental group

Description:

Cohorts 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

Treatment:

Biological: CAR T-Cell Infusion

Cohort 1

Experimental group

Description:

Cohorts 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

Treatment:

Biological: CAR T-Cell Infusion

Cohort II

Experimental group

Description:

Cohorts 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

Treatment:

Biological: CAR T-Cell Infusion

Cohort III

Experimental group

Description:

Cohorts 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

Treatment:

Biological: CAR T-Cell Infusion