Bone Marrow Transplant + GVHD Prophylaxis for Blood Cancer in HIV/AIDS Patients

Overseen By Mustafa A Hyder, M.D.

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must be taking: Antiretrovirals

Must not be taking: Investigational agents

Disqualifiers: Pregnancy, Uncontrolled illness, Active psychiatric disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

265 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug combination to determine if it can safely and effectively prevent graft-versus-host disease (GVHD) in individuals receiving a bone marrow transplant for blood cancer. It specifically targets those living with HIV, who often encounter unique challenges in cancer treatment. Participants must have HIV and a blood cancer treatable with a transplant. Healthy family members are also needed to donate bone marrow. As a Phase 1/Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial group, offering participants a chance to contribute to groundbreaking medical advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, changes to your HIV medication may be needed to avoid interactions with the study drugs, but these changes are not part of the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the drugs used in this study are generally safe for humans. Cyclophosphamide, for example, is commonly used and has been studied in people with blood cancers. Some studies suggest it can help patients live longer without serious problems like GVHD (graft-versus-host disease). However, it might affect the liver, so regular check-ups are important.

Bortezomib is another drug in the study, and research indicates it can reduce the severity of chronic GVHD. Most people tolerate it well, but it might increase the risk of infections.

Maraviroc is approved for treating HIV and is also being studied for preventing GVHD. Research suggests it might help prevent certain complications after a transplant.

Overall, these drugs have been used in other situations with a reasonable safety record. This is a Phase 1/2 trial, meaning safety is still being closely monitored, but early research gives some confidence in the treatment's safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it combines a bone marrow transplant with a reduced-intensity conditioning (RIC) regimen and graft-versus-host disease (GVHD) prophylaxis, specifically for patients with blood cancer who also have HIV/AIDS. Traditional treatments for blood cancer in these patients often involve high-intensity conditioning, which can be very harsh on the body. By using RIC, this approach aims to be less toxic, potentially reducing side effects and improving recovery times. Additionally, the GVHD prophylaxis is tailored to prevent the immune complications that can arise from transplants, which is particularly crucial in immunocompromised individuals like those with HIV/AIDS. Researchers hope this protocol will offer a safer and more effective treatment option for this unique patient group.

What evidence suggests that this trial's treatments could be effective for blood cancer in HIV/AIDS patients?

In this trial, participants will join different treatment arms to evaluate the effectiveness of various combinations. Research has shown that combining cyclophosphamide, maraviroc, and bortezomib may help prevent graft-versus-host disease (GVHD) after bone marrow transplants. Cyclophosphamide is already used in transplants and may benefit HIV patients with blood cancers. Maraviroc, typically an HIV medication, has lowered GVHD rates without adding extra side effects. Bortezomib has effectively treated blood cancers, leading to high survival rates and good blood cell responses. Reduced-intensity conditioning (RIC) is a common method in these transplants that can improve survival for some blood cancers. Together, these treatments aim to make transplants safer and more effective for people with HIV and blood cancer. ^{1 6 7 8 9}

Who Is on the Research Team?

Mustafa A Hyder, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

This trial is for adults over 18 with HIV and blood cancer needing a bone marrow transplant. Eligible patients must have specific types of leukemia, lymphoma, or myeloma in remission or partially responsive to treatment. They need a half-matched family donor aged 12+, good organ function, and controlled HIV with an undetectable viral load.

Exclusion Criteria

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, Failure to qualify per institutional Standard Policies

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning and Transplant Preparation

Participants receive various drugs to prepare their body for the transplant, including eATG, pentostatin, cyclophosphamide, and busulfan.

2 weeks

Transplantation and Initial Treatment

Transplant cells are administered, followed by GVHD prophylaxis with cyclophosphamide, bortezomib, and maraviroc.

6 weeks or longer

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits 1-2 times per week for 3 months after discharge.

3 months

1-2 visits per week

Long-term Follow-up

Participants have visits at 6, 12, 18, 24 months after transplant, then once a year for 5 years to monitor overall survival and other outcomes.

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Bortezomib
• Cyclophosphamide
• Maraviroc
• RIC

Trial Overview

The study tests if cyclophosphamide, maraviroc, and bortezomib can prevent graft-versus-host disease after bone marrow transplants in people with HIV. It's done in two phases: first ensuring safety of the drug combo, then assessing its effectiveness against GVHD.

How Is the Trial Designed?

Group I: 2/Recipient Arm 2 Experimental Treatment 5 Interventions

RIC+alloHCT+GVHD prophylaxis per RP2D

Group II: 1/Recipient Arm 1 Experimental Treatment 5 Interventions

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

Group III: 3/Donor Arm Active Control 1 Intervention

Collection of research samples on hematopoietic donors

RIC is already approved in United States, European Union for the following indications:

Approved in United States as RIC for:

• Hematologic malignancies in HIV-positive patients

Approved in European Union as RIC for:

• Hematologic malignancies in HIV-positive patients

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 292 patients with hematologic malignancies undergoing reduced-intensity conditioning (RIC) followed by allogeneic hematopoietic cell transplantation, the 5-year overall survival rates varied significantly by disease type, with the highest at 78% for indolent non-Hodgkin lymphoma and the lowest at 14% for myeloproliferative neoplasms.

The study found that recipient cytomegalovirus (CMV) positivity was associated with lower relapse rates, particularly when paired with a CMV-positive donor, highlighting the importance of donor-recipient matching in improving transplant outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced-Intensity Conditioning Followed by Related and Unrelated Allografts for Hematologic Malignancies: Expanded Analysis and Long-Term Follow-Up. Warlick, ED., DeFor, TE., Bejanyan, N., et al.[2020]

In a study involving 111 patients with lymphoid and myeloid malignancies, a reduced-intensity conditioning regimen using total lymphoid irradiation and antithymocyte globulin led to durable chimerism in 97% of patients, indicating effective engraftment.

The regimen resulted in low rates of acute graft-versus-host disease (GVHD) (2% for related donors and 10% for unrelated donors) and a nonrelapse mortality rate of less than 4% at one year, suggesting a safe and effective approach for high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TLI and ATG conditioning with low risk of graft-versus-host disease retains antitumor reactions after allogeneic hematopoietic cell transplantation from related and unrelated donors. Kohrt, HE., Turnbull, BB., Heydari, K., et al.[2021]

In a phase II trial involving 17 HIV-positive patients undergoing allogeneic hematopoietic cell transplant, there was no nonrelapse mortality at 100 days, indicating a promising safety profile for this treatment approach.

At one year, the overall survival rate was 59%, and in patients who achieved complete chimerism, HIV DNA and infectious virus were undetectable in the blood, suggesting effective viral control post-transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic Hematopoietic Cell Transplant for HIV Patients with Hematologic Malignancies: The BMT CTN-0903/AMC-080 Trial. Ambinder, RF., Wu, J., Logan, B., et al.[2021]

Nonmyeloablative allogeneic transplantation appears to be a safe and effective treatment for patients with HIV and refractory hematologic malignancies, as demonstrated by two case studies with minimal toxicity and complete remissions achieved in both patients.

Patient 1, who received genetically modified cells, remains in complete remission with undetectable HIV levels and rising CD4 counts over two years post-transplant, indicating potential long-term benefits of this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonmyeloablative conditioning followed by transplantation of genetically modified HLA-matched peripheral blood progenitor cells for hematologic malignancies in patients with acquired immunodeficiency syndrome. Kang, EM., de Witte, M., Malech, H., et al.[2021]

Allogeneic hematopoietic cell transplantation (allo-HCT) shows promising outcomes for people living with HIV, with an overall survival rate of 81.6% at 6 months and 56.6% at 12 months, indicating that their clinical outcomes are comparable to those of patients without HIV.

Reduced-intensity conditioning (RIC) regimens appear to offer a slight survival advantage over myeloablative conditioning (MAC) regimens, suggesting that RIC may be a preferable option for these patients, although further prospective trials are needed to optimize treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risks and Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation for Hematologic Malignancies in Patients with HIV Infection. Arslan, S., Litzow, MR., Cummins, NW., et al.[2021]

Reduced-intensity conditioning (RIC) regimens for allogeneic stem cell transplantation resulted in low early toxicity and stable donor stem cell engraftment, with a 1-year overall survival rate of 60% among 76 patients studied.

While the risk of developing acute graft-versus-host disease (GVHD) was relatively low at 32%, chronic extensive GVHD occurred in 43% of patients, indicating a need for ongoing monitoring and management post-transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning: results of a prospective multicentre study. Martino, R., Caballero, MD., Canals, C., et al.[2019]

Children undergoing reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation (RIC-AlloHSCT) experienced significantly lower rates of acute toxicities, such as mucositis and infections, compared to those receiving myeloablative conditioning (MAC-AlloHSCT), based on a study of 86 patients.

RIC-AlloHSCT also resulted in a lower 100-day transplantation-related mortality (TRM), indicating it may be a safer option for pediatric patients undergoing stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced-intensity conditioning allogeneic stem cell transplantation in pediatric patients and subsequent supportive care. Barrell, C., Dietzen, D., Jin, Z., et al.[2012]

In a study of 101 high-risk patients undergoing reduced-intensity conditioning (RIC) for allogeneic stem cell transplantation, the incidence of acute graft-versus-host disease (aGVHD) was found to be 36%, and chronic graft-versus-host disease (cGVHD) was 43% at 2 years, indicating a significant risk of these complications.

The study revealed that aGVHD was significantly associated with the dose of antithymocyte globulin (ATG) used, while using peripheral blood as a stem cell source was linked to a higher risk of cGVHD; however, the presence of GVHD correlated with a lower risk of disease progression or relapse, suggesting a beneficial graft-versus-tumor effect without increasing transplantation-related mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Graft-versus-host disease following allogeneic transplantation from HLA-identical sibling with antithymocyte globulin-based reduced-intensity preparative regimen. Mohty, M., Bay, JO., Faucher, C., et al.[2021]

In a study of 11 patients with relapsed and refractory lymphoid malignancies, a non-myeloablative allo-SCT regimen using fludarabine and low-dose busulfan allowed for successful engraftment with minimal toxicity, demonstrating a potent graft-versus-tumor (GVT) effect.

Despite the benefits, 72% of patients experienced spontaneous acute graft-versus-host disease (GVHD), but 45% achieved complete remission, indicating that while GVHD is a significant risk, it may be associated with effective tumor response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced intensity conditioning: enhanced graft-versus-tumor effect following dose-reduced conditioning and allogeneic transplantation for refractory lymphoid malignancies after high-dose therapy. Mohty, M., Fegueux, N., Exbrayat, C., et al.[2004]

In a study of 93 patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS), reduced-intensity conditioning (RIC) allo-SCT using fludarabine and busulfan showed promising long-term outcomes, with 4-year disease-free survival (DFS) and overall survival (OS) rates of 43% and 45%, respectively.

The development of chronic graft-versus-host disease (GVHD) was associated with lower relapse rates and improved DFS and OS, highlighting its potential role in enhancing the efficacy of RIC allo-SCT for patients who cannot undergo conventional high-dose conditioning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sustained remissions of high-risk acute myeloid leukemia and myelodysplastic syndrome after reduced-intensity conditioning allogeneic hematopoietic transplantation: chronic graft-versus-host disease is the strongest factor improving survival. Valcárcel, D., Martino, R., Caballero, D., et al.[2013]

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