Phase I Trial Integrating HLA-Haploidentical Anti-CD19 CAR-T Cells With Post-Transplantation Cyclophosphamide-Based HLA-Haploidentical Hematopoietic Cell Transplantation
2 other identifiers
interventional
155
1 country
1
Brief Summary
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. ...
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Nov 2025
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 6, 2025
CompletedFirst Posted
Study publicly available on registry
September 9, 2025
CompletedStudy Start
First participant enrolled
November 14, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2030
ExpectedStudy Completion
Last participant's last visit for all outcomes
October 1, 2034
January 23, 2026
January 21, 2026
5 years
September 6, 2025
January 22, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Identify the safety of anti-CD19 CAR T-cell therapy in combination with HLA-haploidentical HCT in participants with high risk CD19+ hematologic malignancies
Determine the fraction of evaluable recipient participants at each dose level who experience a dose-limiting toxicity (DLT).
28 days (or 35 days for alternate dose levels)
Estimate the 1 year relapse and survival outcomes at the maximum tolerated dose
Estimates will be determined using Kaplan-Meier curves or competing risk-based cumulative incidence curves as appropriate for participants treated at the MTD and may be reported individually for the MTD and other dose levels. The results at indicated time points will be reported and may include 95% confidence intervals as appropriate.
1 year
Secondary Outcomes (6)
Estimate the incidence and severity of CRS and ICANS
100 days
Estimate the incidence of Grade II-IV and Grade III-IV acute GVHD at +200 days
200 days
Estimate the incidence and severity of chronic GVHD at 1 year
1 year
Estimate incidence of primary engraftment failure and kinetics of engraftment
60 days
Estimate relapse/progression, non-relapse mortality, progression-free survival, and overall survival at 1 year
1 year
- +1 more secondary outcomes
Study Arms (3)
Donor
NO INTERVENTIONDonors for Arms 1 and 2
Phase I: Dose Escalation
EXPERIMENTALParticipants receiving CAR-T cells at escalation/de-escalation dose levels to determine MTD
Phase I: Dose Expansion
EXPERIMENTALParticipants receiving CAR-T cells at MTD
Interventions
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.
Pre-transplant: 30 mg/m\^2 IV infusion over 30-60 minutes once daily for 5 days from day -6 through day -2
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.
15 mg/kg orally or IV three times daily (max 1000 mg/dose) starting on day +5, continued through day +35 post-transplant.
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.
Assay used to determine CD19+ status
Assay used to determine CD19+ status
400 centigray (cGy) to be delivered in 2 fractions as 200 cGy per fraction twice a day on Day -1 pre-transplant.
Eligibility Criteria
You may qualify if:
- Participants with high or very high-risk hematologic malignancies, as defined by the revised Disease Risk Index (DRI), or malignancy that remains persistently MRD+ (by flow cytometry, cytogenetics, FISH, PCR, or NGS) on most recently assessed disease specimen (within 2 months of initiating conditioning).
- Hematologic malignancy must be CD19+ (uniform expression on immunohistochemistry or \>= 80% on flow cytometry) as confirmed by CD19 IHC assay (BT51E) or flow cytometry (BD QuantiBRITE(TM) Beads PE Fluorescence Quantitation Kit). (Participants do not have to have refused or lack access to commercial anti-CD19 CAR-T-cell therapies since this study focuses on the integration of CAR-T cells and HCT and not specifically the CAR-T cells themselves; furthermore the construct used to manufacture this product is the same as used in a current commercial product, but developed from a new batch and with a similar but not identical manufacturing process.)
- Age 18-75
- Karnofsky \>= 60%.
- Participants must have adequate organ and marrow function as defined below:
- Cardiac ejection fraction \>= 45% by 2D echocardiography;
- Forced expiratory volume-1 (FEV-1) and diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin) all of \>= 50% predicted;
- Estimated serum creatinine clearance of \>= 60 ml/minute/1.73m\^2 calculated using eGFR in the clinical lab (participants with estimated serum creatinine clearance less than 60 may have measured creatinine clearance performed and if \>= 60 will be considered eligible);
- Total bilirubin \<= 2X the upper limit of normal (participants with documented or suspected Gilbert s are exempt from this requirement);
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<= 5X the upper limit of normal.
- At least one available HLA-haploidentical donor
- Women of child-bearing potential (WOCBP) must agree to use a highly effective method of contraception (hormonal, intrauterine device (IUD), surgical sterilization, abstinence) at the study entry and for 1 year after transplant (restriction period).
- Men must agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) at the study entry and for 1 year after transplant. We also will recommend men with female partners of childbearing potential to ask female partners to be on highly effective birth control (hormonal, intrauterine device (IUD), surgical sterilization). Men must not freeze or donate sperm within the same period.
- Breastfeeding participants must be willing to discontinue breastfeeding from study treatment initiation through 1 year after transplant.
- Participants seropositive for human immunodeficiency virus (HIV) not due to intravenous immunoglobulin, must have been on effective combination anti-retroviral therapy for 6 months and without detectable viral load prior to the beginning of conditioning.
- +6 more criteria
You may not qualify if:
- Participants who are receiving any other investigational agents within 3 weeks prior to the beginning of conditioning.
- Active CNS involvement of primary hematologic malignancy
- Active malignancy of non-hematopoietic type (excluding non-melanoma skin cancers) which is metastatic, relapsed/refractory to treatment, or locally advanced and not amenable to intended curative treatment per standard of care.
- Prior checkpoint inhibitor therapy within 6 weeks prior to the beginning of conditioning.
- Prior history of seizure.
- Uncontrolled infection.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agents used in study.
- Uncontrolled intercurrent illness evaluated by medical history, physical exam, EKG, and laboratory testing (e.g., severe endocrinopathy, disseminated intravascular coagulation, profound electrolyte disturbance) that would make it unsafe to proceed with transplantation.
- \. Pregnancy
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Christopher G Kanakry, M.D.
National Cancer Institute (NCI)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 6, 2025
First Posted
September 9, 2025
Study Start
November 14, 2025
Primary Completion (Estimated)
November 1, 2030
Study Completion (Estimated)
October 1, 2034
Last Updated
January 23, 2026
Record last verified: 2026-01-21
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Data will be made available as soon as possible or at the time of associated publication. Data not published in a manuscript will be shared via public source once the data set completes QC.
- Access Criteria
- Clinical data will be made available upon request and with the permission of the study PI. Genomic data are made available via dbGAP through requests to the data custodians.
This study will comply with the NIH Data Management and Sharing (DMS) Policy, which applies to all new and ongoing NIH-funded research in the IRP, as of January 25, 2023, that is associated with a ZIA, with a clinical protocol that undergoes scientific review and/or will involve genomic data sharing.