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

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ClinicalTrials.gov Identifier: NCT04556266
Recruitment Status : Recruiting
First Posted : September 21, 2020
Last Update Posted : September 21, 2020
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Leukemia Lymphoma Lymphoma, B-Cell Biological: CAR T-Cell Infusion Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : September 14, 2020
Estimated Primary Completion Date : September 14, 2023
Estimated Study Completion Date : September 14, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cohort -1

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

Biological: CAR T-Cell Infusion
Dose Level -1: 1 x 10^4 cells/kg Dose Level 1: 1 x 10^5 cells/kg Dose Level 2: 2 x 10^5 cells/kg Dose Level 3: 4 x 10^5 cells/kg

Experimental: Cohort 1

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

Biological: CAR T-Cell Infusion
Dose Level -1: 1 x 10^4 cells/kg Dose Level 1: 1 x 10^5 cells/kg Dose Level 2: 2 x 10^5 cells/kg Dose Level 3: 4 x 10^5 cells/kg

Experimental: Cohort II

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

Biological: CAR T-Cell Infusion
Dose Level -1: 1 x 10^4 cells/kg Dose Level 1: 1 x 10^5 cells/kg Dose Level 2: 2 x 10^5 cells/kg Dose Level 3: 4 x 10^5 cells/kg

Experimental: Cohort III

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

Biological: CAR T-Cell Infusion
Dose Level -1: 1 x 10^4 cells/kg Dose Level 1: 1 x 10^5 cells/kg Dose Level 2: 2 x 10^5 cells/kg Dose Level 3: 4 x 10^5 cells/kg




Primary Outcome Measures :
  1. Maximum tolerated dose (MTD) [ Time Frame: 24 month ]
    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



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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04556266


Contacts
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Contact: Melody Smith, MD 212-639-5787 smithm4@mskcc.org
Contact: Miguel-Angel Perales, MD 646-608-3757 peralesm@mskcc.org

Locations
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United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Melody Smith, MD    212-639-5787      
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Investigators
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Principal Investigator: Melody Smith, MD Memorial Sloan Kettering Cancer Center
Additional Information:
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Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT04556266    
Other Study ID Numbers: 17-331
First Posted: September 21, 2020    Key Record Dates
Last Update Posted: September 21, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Memorial Sloan Kettering Cancer Center:
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
Additional relevant MeSH terms:
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Lymphoma
Neoplasms
Lymphoma, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin