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 ...

Summary

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.

Conditions

• HIV
• Hematologic Malignancies

Interventions

DRUG

RIC

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.

DRUG

GVHD prophylaxis

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

PROCEDURE

allo HCT

bone marrow transplant

DRUG

Plerixafor

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

DRUG

Maraviroc

Phase 1 dose level 2: 300 mg orally twice daily starting day-3 through day day+30

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Mustafa A Hyder, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

12 Years

Max Age

120 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2023-01-26

Primary Completion

2026-07-30

Completion

2027-07-30

FDA Drug

Yes

Countries

• United States

Study Locations