Trial of Allogeneic Reduced-Intensity, HLA-Haploidentical Allogeneic Hematopoietic Cell Bone Marrow Transplantation Followed by Graft-versus-Host-Disease (GVHD) Prophylaxis With Cyclophosphamide, Bortezomib and Maraviroc for Hematologic Malignancies ...

Part of paid clinical trials in Bethesda, Maryland.

Sponsor
National Cancer Institute (NCI)
Study ID
NCT05470491
Phase
PHASE1/PHASE2
Status
Recruiting
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Conditions

  • HIV
  • Hematologic Malignancies

Eligibility Criteria

Sex
ALL
Age
12 Years - 120 Years
Healthy Volunteers
Accepted

Interventions

  • RIC — DRUG
    e-ATG 40 mg/kg/day IV on days -14 and -13. Prednisone tapering doses given orally daily: -days -14 through -12: 1mg/kg/day -days -11 and -10: 0.75 mg/kg/day -days -9 and -9: 050 mg/kg/day -day -7: 0.25 mg/kg/day Pentostatin 4 mg/m2/day IV on days -11 and -7. Cyclophosphamide 5 mg/kg orally or IV daily on days -11 through -4. Busulfan IV AUC targeted dose of 14.8-23.0 mg\*h/L, on days -3 and -2.
  • GVHD prophylaxis — DRUG
    Cyclophosphamide 50 mg/kg IV daily Bortezomib 1.3 mg/m2 IV +6 hours and +72 hours after graft infusion Mesna 50 mg/kg IV concomitant with cyclophosphamide
  • allo HCT — PROCEDURE
    bone marrow transplant
  • Plerixafor — DRUG
    In phase 1 dose level 3 and phase 2 only: Plerixafor 240 (Micro)g/kg subcutaneously every other day, starting day +1 through day +21
  • Maraviroc — DRUG
    Phase 1 dose level 2: 300 mg orally twice daily starting day-3 through day day+30

Study Details

Background: People living with HIV(PLWH) are at a higher risk for cancers that may be curable with a bone marrow transplant. HIV infection itself is no longer a reason to not get a transplant, for patients who otherwise have a standard reason to need transplant. Objective: This study is being done to see if a new combination of drugs (cyclophosphamide, maraviroc, and bortezomib) is both safe and effective at protecting against graft-versus-host disease after bone marrow transplant. The study will also test the transplant s impact on your survival and control of your cancer. Eligibility: People aged 18 years and older living with HIV and a blood cancer that is eligible for a transplant. Healthy family members aged 12 or older who are half matched to transplant recipients are also needed to donate bone marrow. Design: The study will be done in 2 phases. The first phase will be to see if we can safely use a new combination of drugs to prevent GVHD. If the combination is safe in the first phase, the study will proceed to the second phase. In the second phase, we will see if this new combination can better protect against GVHD after transplant. Participants will be screened. Their diagnoses, organ function and eligibility will be confirmed. Participants will have a catheter inserted into a vein in their chest or neck. Medications and transfusions will be given through the catheter; blood will be drawn from it. Participants will be in the hospital for 6 weeks or longer. They will receive various drugs for 2 weeks to prep their body for the transplant. The transplant cells will be administered through the catheter. Participants will continue to receive drug treatments after the transplant. Blood transfusions may also be needed. Participants will return 1-2 times per week for follow-up visits for 3 months after discharge. Participants will have visits 6, 12, 18, 24 months after transplant, then once a year for 5 years.

Key Dates

Start date
Jan 26, 2023
Status verified
May 2026
Primary completion
Jul 30, 2026
Completion
Jul 30, 2027

Study Design

Enrollment
265 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: 1/Recipient Arm 1
    RIC+alloHCT+GVHD prophylaxis per dose levels 1, 2, and
  • Experimental: 2/Recipient Arm 2
    RIC+alloHCT+GVHD prophylaxis per RP2D
  • No Intervention: 3/Donor Arm
    Collection of research samples on hematopoietic donors

Primary Outcome Measure

In phase II, avoidance rate of grade III-IV acute GVHD at day +100 [ Time Frame: day +100 post HCT ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
National Institutes of Health Clinical CenterBethesdaMaryland20892
For more information at the NIH Clinical Center contact National Cancer Institute Referral Office
888-624-1937

Find similar trials in Bethesda, MD

By condition
HIV
By specialty
Infectious disease
By research site
National Institutes of Health Clinical Center· Bethesda, MD

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