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Protocol Details

A Phase I/II Trial of Allogeneic Reduced-Intensity, HLA-Haploidentical Bone Marrow Transplantation Followed by GVHD Prophylaxis with Cyclophosphamide, Bortezomib and Maraviroc for Hematologic Malignancies in People Living with HIV (PLWH)

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

000478-C

Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 12 Years
Max Age: N/A

Referral Letter Required

No

Population Exclusion(s)

Pregnant Women;
Fetuses

Keywords

Hematopoietic Cell Transplant;
HCT;
Human Immunodeficiency Virus

Recruitment Keyword(s)

None

Condition(s)

HIV;
Hematologic Malignancies

Investigational Drug(s)

Pentostatin
Maraviroc

Investigational Device(s)

None

Intervention(s)

Drug: RIC
Drug: GVHD prophylaxis
Procedure/Surgery: allo HCT
Drug: Plerixafor
Drug: Maraviroc

Supporting Site

National Cancer Institute

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.

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Eligibility

ELIGIBILITY CRITERIA:

Inclusion Criteria - Recipient:

-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)

--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

--Hematologic malignancy of dendritic cell or histiocytic cell type

--Multiple myeloma that relapses after therapy with both a proteasome inhibitor and an immunomodulatory drug (IMiD), relapses after autologous transplantation, or manifests as plasma cell leukemia

In addition to standard indications for HCT: Participant with a hematologic malignancy eligible for consolidation of first remission with autologous transplantation, if autologous transplantation is not accessible to the participant.

-HIV seropositive, with ART regimen that is stable for >4 weeks and HIV viral load <400 copies/mL

--Dose level 1: ART regimen must include maraviroc

--Dose level 2 and 3: ART regimen must not include maraviroc and there must be no history of maraviroc intolerance or resistance

-Age >= 18 years

-At least one potentially suitable HLA-haploidentical first degree or collateral related donor. Recipients with donor-specific anti-HLA antibodies (DSAs) to all potential donors must have at least one potential donor option where the DSA strength has a mean fluorescence intensity of < 5000 and antibodies are not complement-fixing.

-Karnofsky performance score >=50% (see APPENDIX A: Performance Status Criteria).

-Adequate organ function defined as possessing all of the following:

--Cardiac ejection fraction by 2D ECHO of >=40%

--Forced expiratory volume-1 (FEV-1), forced vital capacity (FVC), and diffusing capacity of the lung for carbon monoxide (DLco, adjusted for hemoglobin) all of >=40% predicted. If unable to perform pulmonary function tests, there should be no evidence of dyspnea at rest, no requirement for supplemental oxygen, and oxygen saturation >92% on room air. Calculations will be based on the USA-ITS-NIH reference.

--Total bilirubin <=3.0 mg/dL (unless due to Gilbert s or hemolysis), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) <= 5x the upper ma glutamyl transferase (GGT) <= 5x the upper limit of normal

-Estimated serum creatinine clearance of >=50 mL/min/1.73m2 calculated using eGFR in the clinical lab

-Ability of participant to understand and the willingness to sign a written informed consent document.

-Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for at least one-year post-allo HCT.

Inclusion criteria - Related Donor:

-Related donor (age >=12) deemed suitable and eligible, and willing to donate, per clinical evaluations, who are additionally willing to donate blood and/or bone marrow for 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.

EXCLUSION CRITERIA:

Exclusion Criteria - Recipient:

-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% or active extramedullary disease)

--Lymphoma not having achieved at least a partial response to prior chemotherapy or radiation 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% 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 women: 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

Exclusion Criteria - Related Donor:

-Failure to qualify per institutional Standard Policies


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Citations:

Not Provided

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Contacts:

Principal Investigator

Referral Contact

For more information:

Jennifer A. Kanakry, M.D.
National Cancer Institute (NCI)
NIHBC 10 - CRC BG RM 4-3132
10 CENTER DR
BETHESDA MD 20892
(240) 858-9255
jennifer.kanakry@nih.gov

Jessenia C. Campos, R.N.
National Cancer Institute (NCI)
National Institutes of Health
Building 10
Room 4-3152
10 Center Drive
Bethesda, Maryland 20892
(240) 858-7492
jessenia.campos@nih.gov

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
1-888-NCI-1937

Clinical Trials Number:

NCT05470491

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