HST-NEETs + Bone Marrow Transplant for Lymphoma

(BMTCTN1903 Trial)

Not currently recruiting at 16 trial locations

Overseen By Christine Borchert

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Catherine Bollard

Must be taking: Antiretroviral therapies

Must not be taking: Steroids

Disqualifiers: HIV subtype other than B, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 101

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment approach for individuals with HIV-related lymphoma, a cancer affecting the immune system. The study aims to evaluate the effectiveness of combining bone marrow transplants with a new therapy called HST-NEETs after high-dose chemotherapy. It targets those who are HIV positive, have certain types of lymphoma unresponsive to previous treatments, and plan to undergo a specific type of stem cell transplant. Participants must have shown at least partial response to recent chemotherapy and have their HIV controlled with medication. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must be on antiretroviral therapy (ART) with a controlled HIV viral load to participate.

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

Research has shown that Busulfan, a drug used in bone marrow transplants, is usually well-tolerated. It may cause mild to moderate side effects, such as increased liver enzymes, which indicate liver stress but are typically not serious.

In past studies using a patient's own stem cells for transplants, many patients remained disease-free for extended periods, although some experienced a recurrence. This suggests the treatment can be effective for some, but it also highlights the importance of closely monitoring patients.

Overall, while risks exist, the treatments in this trial have proven safe and beneficial for many when managed carefully. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lymphoma?

Researchers are excited about HST-NEETs in the treatment of lymphoma because it offers a unique approach by targeting the immune system's ability to fight cancer cells, specifically in HIV-positive patients. Unlike traditional chemotherapy or radiation therapies that primarily attack cancer cells directly, HST-NEETs involve an autologous hematopoietic stem cell transplant, which rejuvenates the patient's own immune system to better combat the disease. This method could potentially lead to more sustainable remission by harnessing the body's natural defenses, providing a new avenue for those with limited options.

What evidence suggests that this trial's treatments could be effective for lymphoma?

Research has shown that using HST-NEETs after a bone marrow transplant might help treat HIV-related lymphoma. This trial will evaluate the effectiveness of HST-NEETs in this context. This method can reduce the HIV reservoir in the body, cutting down the virus's hiding spots. Previous patients handled HST-NEETs well, indicating it can be safe. Additionally, survival rates for similar stem cell transplants are encouraging, with about 60% of patients with certain types of lymphoma living at least five years after treatment. These findings offer hope that combining HST-NEETs with a bone marrow transplant could be effective. ^{1 5 6 7 8}

Who Is on the Research Team?

Steve Devine, MD, MS

Principal Investigator

National Marrow Donor Program

Are You a Good Fit for This Trial?

This trial is for individuals at least 15 years old with HIV-associated lymphoma, specifically those who have had two or three prior treatments and are responsive to chemotherapy. They must be planning an autologous stem cell transplant (ASCT) and have a Karnofsky performance status of 70% or higher. People with uncontrolled infections, previous cellular therapies, certain heart conditions, resistant HIV strains, or active CNS involvement cannot participate.

Inclusion Criteria

My HIV is under control with medication.

I do not have any infections that aren't under control.

I am at least 15 years old.

Exclusion Criteria

My cancer has spread to my brain or spinal cord.

I am taking more than 0.5 mg/kg/day of steroids.

My HIV is not subtype B.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-transplant Conditioning

Participants undergo BEAM conditioning regimen prior to ASCT

6 days

Daily visits for conditioning administration

Autologous Stem Cell Transplantation (ASCT)

Participants receive autologous stem cell transplant on Day 0

1 day

Inpatient procedure

HST-NEETs Administration

Participants receive HST-NEETs between Days +3 to +7 post-ASCT

1 week

1 visit for infusion

Follow-up

Participants are monitored for safety, effectiveness, and various outcomes post-ASCT

1 year

Regular visits at Day 100, 6 months, and 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Bone Marrow Transplant
• Busulfan
• HST-NEETs

Trial Overview The trial is testing the effectiveness of HST-NEETs following an autologous stem cell transplant in treating HIV-related lymphomas. It's a Phase II study where all participants receive high-dose chemotherapy followed by ASCT and then the investigational therapy HST-NEETs.

How Is the Trial Designed?

Group I: HST-NEETs Experimental Treatment 2 Interventions

HIV+ Participants that were treated with autologous hematopoietic stem cell transplant.

Bone Marrow Transplant is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Allogeneic Bone Marrow Transplant for:

• Acute Leukemias
• Chronic Leukemias
• Lymphomas
• Multiple Myeloma
• Myelodysplastic Syndromes
• Aplastic Anemia

Approved in United States as Allogeneic Bone Marrow Transplant for:

• Acute Leukemias
• Chronic Leukemias
• Lymphomas
• Multiple Myeloma
• Myelodysplastic Syndromes
• Aplastic Anemia

Approved in Canada as Allogeneic Bone Marrow Transplant for:

• Acute Leukemias
• Chronic Leukemias
• Lymphomas
• Multiple Myeloma
• Myelodysplastic Syndromes
• Aplastic Anemia

Approved in Japan as Allogeneic Bone Marrow Transplant for:

• Acute Leukemias
• Chronic Leukemias
• Lymphomas
• Multiple Myeloma
• Myelodysplastic Syndromes
• Aplastic Anemia

Who Is Running the Clinical Trial?

Catherine Bollard

Lead Sponsor

Trials

1

Recruited

10+

National Marrow Donor Program

Collaborator

Trials

63

Recruited

202,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Blood and Marrow Transplant Clinical Trials Network

Collaborator

Trials

51

Recruited

14,600+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Children's National Research Institute

Collaborator

Trials

227

Recruited

258,000+

Published Research Related to This Trial

Intravenous busulfan, used as a conditioning treatment before hematopoietic stem cell transplantation in pediatric patients, effectively achieves targeted therapeutic plasma levels, leading to high rates of sustained engraftment and low transplant-related mortality.

This formulation is well tolerated, with fewer severe adverse effects compared to oral busulfan, particularly showing a lower incidence of severe hepatic veno-occlusive disease (HVOD) and organ toxicity, making it a safer option for young patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous busulfan: in the conditioning treatment of pediatric patients prior to hematopoietic stem cell transplantation. Hoy, SM., Lyseng-Williamson, KA.[2018]

In a study of 119 adult patients with acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplantation, the TBI/Cy conditioning regimen resulted in a median overall survival of 11 months, compared to 6.2 months for the Bu/Cy regimen.

Although both conditioning regimens showed no statistically significant differences in overall survival and disease-free survival, the Bu/Cy regimen was associated with a higher risk of relapse, indicating a potential disadvantage in using this non-TBI approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irradiation free conditioning regimen is associated with high relapse rate in Egyptian patients with acute lymphoblastic leukemia following allogeneic hematopoietic stem cell transplantation. Abdelaty, MM., Gawaly, A., Fathy, GM., et al.[2021]

The BUCY regimen, combining busulfan and cyclophosphamide, was found to be safe for autologous hematopoietic stem cell transplantation in 20 patients with multiple myeloma, with no treatment-related mortality within 100 days post-transplant.

Hematopoietic recovery was prompt, with neutrophil and platelet counts returning to normal within 8 to 18 days, and all patients survived the treatment, although the partial remission rate dropped significantly after transplantation, indicating the need for further long-term monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Busulfan Combined with Cyclophosphamide as the Conditioning Regimen in Patients with Multiple Myeloma Treated by Autolo-gous Hematopoietic Stem Cell Transplantation]. Jin, S., Xu, Y., Wang, PF., et al.[2018]

Nonmyeloablative doses of parenteral busulfan demonstrated significant hematologic toxicity, particularly during the second to third week after administration, but were less toxic than myeloablative total body irradiation (TBI).

Busulfan facilitated over 70% donor leukocyte engraftment with a dose of just 20 mg/kg, and this level of engraftment was achievable even when hematopoietic stem cells were infused up to 20 days after busulfan treatment, indicating a flexible time window for HSC infusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose parenteral busulfan provides an extended window for the infusion of hematopoietic stem cells in murine hosts. Hsieh, MM., Langemeijer, S., Wynter, A., et al.[2019]

Citations

1. withpower.com withpower.com/trial/phase-3-lymphoma-aids-related-9-2021-9f149

HST-NEETs + Bone Marrow Transplant for Lymphoma Trial Overview The trial is testing the effectiveness of HST-NEETs following an autologous stem cell transplant in treating HIV-related lymphomas. It's a Phase ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04975698

Study Details | NCT04975698 | HIV Antigen-specific T-cells ... Feasibility is defined as a participant receiving HST-NEETs within 1 week post-ASCT; Efficacy will be measured by the reduction in intact proviral reservoir. ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/24096123/

Outcomes of autologous or allogeneic stem cell ... - PubMed Five-year overall survival rates for B and T cell NHL were 58% and 50%, respectively (allo-SCT 51% vs. 54% for B and T-cell NHL, and auto-SCT 60% vs. 47% for B ...

4. bmtctn.net bmtctn.net/system/files/1903%20HIV%20TCell%20FAQs_v4.0_0.pdf

BMT CTN PROTOCOL #1903 (HIV T-cell) This is potentially an ideal setting to test HST-NEETs as the lymphodepletion induced by high dose chemotherapy may promote greater in-vivo ...

5. nature.com nature.com/articles/s41467-025-59810-2

Autologous HIV-specific T cell therapy targeting conserved ... We report that two infusions of autologous HST-NEETs in six adults with HIV on ART is well-tolerated following >45 weeks of safety monitoring post infusions.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9302266/

Long-Term Outcomes and Safety Trends of Autologous Stem ... At the last follow-up, 39 (48.7%) patients were disease-free, 27 (33.7%) died due to disease progression, and two (2.5%) were alive with ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04975698?term=AREA%5BBasicSearch%5D(AREA%5BBasicSearch%5D(AREA%5BBasicSearch%5D(AREA%5BConditionSearch%5D(%22Lymphoma,%20AIDS-Related%22))))&rank=6

HIV Antigen-specific T-cells Targeting Conserved Epitopes (HST ... A phase of research to describe clinical trials that focus on the safety of a drug. They are usually conducted with healthy volunteers, and the goal is to ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38431075/

A US Multicenter Collaborative Study on Outcomes ... Hepatosplenic T-cell lymphoma (HSTCL) is a rare and aggressive type of peripheral T-cell lymphoma with median overall survival (OS) of ...