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 ...

NCT05470491 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 10000478000478-C
• Study Type: interventional
• Target: 265
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

Hematopoietic Cell Transplant; HCT; Human Immunodeficiency Virus

Outcome Measures

Primary Outcomes (2)

• In phase II, avoidance rate of grade III-IV acute GVHD at day +100

  Proportion of evaluable recipients who experience grade III-IV acute GVHD at day +100 will be reported along with 80% and 95% two-sided confidence interval

  day +100 post HCT

• Determine a safe and recommended phase II dose level regimen

  Number and type of toxicities noted for participants who are evaluable

  day +100 post HCT

Secondary Outcomes (9)

• Cumulative incidence of primary and secondary graft failure

  day +100 and 1 year post HCT

• Cumulative incidence of hematopoietic recovery

  day +100

• Overall Survival

  1, 2, 3, 4, and 5 years post HCT

• Cumulative incidence of relapse

  1, 3, and 5 years post HCT

• GVHD-free, relapse free survival (GRFS)

  1, 3, and 5 years post HCT

Study Arms (3)

1/Recipient Arm 1

EXPERIMENTAL

RIC+alloHCT+GVHD prophylaxis per dose levels 1, 2, and

Drug: RIC; Drug: GVHD prophylaxis; Procedure: allo HCT; Drug: Plerixafor; Drug: Maraviroc

2/Recipient Arm 2

EXPERIMENTAL

RIC+alloHCT+GVHD prophylaxis per RP2D

Drug: RIC; Drug: GVHD prophylaxis; Procedure: allo HCT; Drug: Plerixafor; Drug: Maraviroc

3/Donor Arm

NO INTERVENTION

Collection of research samples on hematopoietic donors

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.

1/Recipient Arm 1; 2/Recipient Arm 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

1/Recipient Arm 1; 2/Recipient Arm 2

allo HCT PROCEDURE

bone marrow transplant

1/Recipient Arm 1; 2/Recipient Arm 2

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

1/Recipient Arm 1; 2/Recipient Arm 2

Maraviroc DRUG

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

1/Recipient Arm 1; 2/Recipient Arm 2

Eligibility Criteria

• Age: 12 Years - 120 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have a histologically or cytologically confirmed hematologic malignancy with standard indication for allogeneic hematopoietic cell transplantation including, but not limited to, one of the following:
• Acute myeloid leukemia in morphologic complete remission (\<5% blasts in the bone marrow, no detectable abnormal peripheral blasts, and no extramedullary disease)
• Any secondary and/or treatment related myeloid neoplasm with antecedent history of myeloid neoplasm or previous chemotherapy/radiation
• B-cell acute lymphoblastic leukemia in first or subsequent complete remission
• T-cell acute lymphoblastic leukemia in first or subsequent complete remission
• Myelodysplastic syndrome of intermediate or higher score by the Revised International Prognostic Scoring System (IPSS-R)
• Primary myelofibrosis of intermediate-2 or higher risk by the Dynamic IPSS-Plus (DIPSS-Plus) or high to very high risk score (5 or higher) calculated with MIPSS70+ Calculator; DIPSS-Plus For Myeloproliferative Neoplasms on the Mutation Enhanced International Prognostic Score System (MIPSS70/MIPSS70+)
• Chronic myelomonocytic leukemia
• Chronic myelogenous leukemia resistant to or intolerant of \>=3 tyrosine kinase inhibitors or with history of accelerated phase or blast crisis
• B-cell lymphoma including Hodgkin lymphoma that has relapsed/progressed within 1 year of completion of primary treatment, after autologous transplantation or has progressed through at least 2 lines of therapy
• Burkitt or lymphoblastic lymphoma: high-risk disease in first remission, progression/relapse after \>=1 previous regimen
• Chronic lymphocytic leukemia with 17p deletion and/or unmutated IgHv or refractory or intolerant of both BTK and PI3K inhibitors
• Mature T or NK neoplasms as defined in the WHO guidelines of sufficient type and severity for allogeneic HCT based on published clinical practice guidelines
• T-Prolymphocytic leukemia progressing/relapsing after alemtuzumab and at least one other regimen
• B-Prolymphocytic leukemia progressing/relapsing after fludarabine and at least one other salvage regimen

You may not qualify if:

• Participants who are receiving any other investigational agents that cannot be discontinued/completed at least 2 weeks prior to the date of beginning conditioning.
• Poorly controlled malignant indication for transplantation, defined as:
• Leukemia not having achieved morphologic remission (i.e. bone marrow blasts \>5 percent or active extramedullary disease)
• Lymphoma not having demonstrated some degree of treatment sensitivity (chemosensitivity, radiosensitivity) by clinical and/or radiologic assessment
• Multiple myeloma not in complete remission, as determined by negative immunofixation in serum and urine and disappearance of any soft tissue plasmacytomas and \<= 5 percent plasma cells in the bone marrow.
• Uncontrolled intercurrent illness that in the opinion of the PI would make it unsafe to proceed with transplantation.
• Study team is unable to identify an adequate antiretroviral regimen to adequately suppress the HIV viral load \<400 copies/mL that is compatible with study drugs
• Pregnancy
• For lactating potential participants: unwilling to discontinue lactation prior to the start of study treatment on day -14.
• Prohibitive allergy to a study drug or to compounds of similar chemical or biologic composition of the agents (eATG, steroids, cyclophosphamide, busulfan, pentostatin, maraviroc, bortezomib, plerixafor (dose level 3 only)) used in the study.
• Lack of central access potential sufficient for transplant
• Active psychiatric disorder which is deemed by the PI to have significant risk of compromising compliance with the transplant protocol and/or antiretroviral therapy
• Grade 3-4 motor or sensory neuropathy per CTCAE version 5.0
• Related donor (age \>=12) deemed suitable and eligible, and willing to donate, per clinical evaluations, who are additionally willing to donate blood and/or PBSC graft aliquotfor research. Related donors will be evaluated in accordance with existing institutional Standard Policies and Procedures for determination of eligibility and suitability for clinical donation.
• Ability of participant or parent/legal guardian to understand and the willingness to sign a written informed consent document.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Hematologic Neoplasms; Acquired Immunodeficiency Syndrome

Interventions

plerixafor; Maraviroc

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Mustafa A Hyder, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jessenia C Campos, R.N.

CONTACT

(240) 858-7492; jessenia.campos@nih.gov

Mustafa A Hyder, M.D.

CONTACT

(240) 858-3182; mustafa.hyder@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2022
• First Posted: July 22, 2022
• Study Start: January 26, 2023
• Primary Completion (Estimated): July 30, 2026
• Study Completion (Estimated): July 30, 2027
• Last Updated: June 8, 2026

Record last verified: 2026-05-20

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as the database is active
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with permission of the study PI. Genomic data are made available via dbGAP through requests to the data custodians

Locations

US (1)