Phase I Trial Integrating HLA-Haploidentical Anti-CD19 CAR-T Cells With Post-Transplantation Cyclophosphamide-Based HLA-Haploidentical Hematopoietic Cell Transplantation

Part of paid clinical trials in Bethesda, Maryland.

Sponsor
National Cancer Institute (NCI)
Study ID
NCT07162038
Phase
PHASE1
Status
Recruiting
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Conditions

  • Hematologic Malignancies
  • Hematologic Neoplasms

Eligibility Criteria

Sex
ALL
Age
18 Years - 75 Years
Healthy Volunteers
Not accepted

Interventions

  • mCD19-CAR-CD28-CD3-zeta.(anti-CD19 CAR) retroviral vector-transduced allogeneic peripheral blood lymphocytes (PBL) — BIOLOGICAL
    CAR-T cell infusion given at four escalating dose levels (DL1: 3 x 10\^4 cells/kg, DL2: 1 x 10\^5 cells/kg, DL3: 3 x 10\^5 cells/kg, DL4: 1 x 10\^6 cells/kg) with a dose de-escalation dose (DL-1: 1 x 10\^4 cells/kg), if needed.
  • Fludarabine — DRUG
    Pre-transplant: 30 mg/m\^2 IV infusion over 30-60 minutes once daily for 5 days from day -6 through day -2
  • Cyclophosphamide — DRUG
    Pre-transplant: 14.5 mg/kg/day IV daily for 2 days pre-transplant on day -6 and day -5. Post-transplant: 25 mg/kg/day on day +3 and day +4.
  • Mycophenolate Mofetil — DRUG
    15 mg/kg orally or IV three times daily (max 1000 mg/dose) starting on day +5, continued through day +35 post-transplant.
  • Sirolimus — DRUG
    Loading dose of 6 mg orally given on day +5, then maintenance dose starting at 2 mg orally daily on day +6 with dose adjustments to maintain a trough of 5-12 ng/ml, continued through day +60 post-transplant.
  • CD19 Flow Cytometry Assay — DEVICE
    Assay used to determine CD19+ status
  • CD19 Immunohistochemical Assay — DEVICE
    Assay used to determine CD19+ status
  • Total Body Irradiation — RADIATION
    400 centigray (cGy) to be delivered in 2 fractions as 200 cGy per fraction twice a day on Day -1 pre-transplant.

Study Details

Background: High-risk blood cancers (leukemias and lymphomas) often come back after treatment, and many cannot be cured with chemotherapy alone. These cancers may be treated and potentially cured in 2 ways: (1) Bone marrow transplant (allogeneic hematopoietic cell transplantation, or alloHCT) gives immune and blood stem cells from a donor. These new cells can attack the cancer and also grow into healthy blood. (2) Chimeric antigen receptor (CAR) T-cell therapy takes immune cells and changes them in a lab to better recognize and target certain cancers. But these 2 treatments are not usually given at the same time. Objective: To test alloHCT and CAR-T cell therapy, used together, in people with high-risk blood cancers. Eligibility: People aged 18 to 75 years with an aggressive blood cancer that has a protein on the surface called CD19. A healthy related donor aged 12 years or older is also needed; this donor may be a parent or child or may be some siblings or even extended family members, but has to be half-matched at something called the HLA (human leukocyte antigen). Design: Participants will be screened. They will have imaging scans, blood tests, and tests of their heart and lung function. They will have eye and dental exams. They may have fluid drawn from around their spinal cord (spinal tap) and tissue taken from inside a bone (bone marrow biopsy). Healthy donors will provide bone marrow, immune cells, and about 9 tablespoons of blood for both the recipient s treatment and for research. They will also provide stool, saliva, and oral swabs just for research. Recipient participants will stay in the hospital for 4 to 6 weeks. They will be given drugs over 6 days to prepare for the cell therapies. Both the donor bone marrow cells and CAR-T-cells will be given through a tube inserted into a vein. They will receive drugs to reduce complications after the treatments. Participants will remain within a 1-hour drive of the hospital for 2 to 3 months after they leave the hospital. They will have frequent visits during that time. They will continue to have periodic follow-up visits for 5 years. ...

Key Dates

Start date
Nov 14, 2025
Status verified
Jun 2026
Primary completion
Nov 1, 2030
Completion
Oct 1, 2034

Study Design

Enrollment
155 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • No Intervention: Donor
    Donors for Arms 1 and 2
  • Experimental: Phase I: Dose Escalation
    Participants receiving CAR-T cells at escalation/de-escalation dose levels to determine MTD
  • Experimental: Phase I: Dose Expansion
    Participants receiving CAR-T cells at MTD

Primary Outcome Measure

Identify the safety of anti-CD19 CAR T-cell therapy in combination with HLA-haploidentical HCT in participants with high risk CD19+ hematologic malignancies [ Time Frame: 28 days (or 35 days for alternate dose levels) ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
National Institutes of Health Clinical CenterBethesdaMaryland20892
National Cancer Institute Referral Office
[email protected]
888-624-1937

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By research site
National Institutes of Health Clinical Center· Bethesda, MD

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