HST-NEETs + Bone Marrow Transplant for Lymphoma

(BMTCTN1903 Trial)

Recruiting at 15 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

12 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment HST-NEETs + Bone Marrow Transplant for Lymphoma?

Research shows that bone marrow transplants, especially from HLA-matched donors, have been effective in treating various blood-related conditions, including lymphomas. In one study, patients with Hodgkin's or non-Hodgkin's lymphoma who received bone marrow transplants with busulfan and cyclophosphamide had some long-term disease-free survival, indicating potential effectiveness for this treatment. ^{1 2 3 4 5}

Is the combination of HST-NEETs and Bone Marrow Transplant generally safe for humans?

Busulfan, a drug used in bone marrow transplants, is generally well tolerated in humans, with mild to moderate side effects like elevated liver enzymes. Serious organ toxicity is rare, especially with intravenous busulfan, which is considered safer than the oral form. ^{3 6 7 8 9}

How does the HST-NEETs + Bone Marrow Transplant treatment for lymphoma differ from other treatments?

The HST-NEETs + Bone Marrow Transplant treatment is unique because it combines a bone marrow transplant with busulfan, a drug used to prepare the body for the transplant by reducing the immune response and making space for new cells. This approach is different from traditional treatments that often use high-dose chemoradiotherapy, as it aims to reduce toxicity while still achieving effective donor cell engraftment. ^{1 10 11 12 13}

What is the purpose of this trial?

This is a Phase II multi-center trial single arm trial of autologous transplantation (ASCT) followed by administration of HST-NEETs for treatment of HIV associated lymphoma

Research Team

Steve Devine, MD, MS

Principal Investigator

National Marrow Donor Program

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Bone marrow transplantation as treatment for X-linked immunodeficiency with hyper-IgM. [2010]

2. England pubmed.ncbi.nlm.nih.gov

Preparation for marrow transplantation in Hodgkin's and non-Hodgkin's lymphoma using Bu/CY. [2013]

3. United States pubmed.ncbi.nlm.nih.gov

High-dose busulfan in patients with myeloma. [2017]

4. United States pubmed.ncbi.nlm.nih.gov

Comparison of outcomes of allogeneic transplantation for chronic myeloid leukemia with cyclophosphamide in combination with intravenous busulfan, oral busulfan, or total body irradiation. [2018]

5. Australia pubmed.ncbi.nlm.nih.gov

Bone marrow transplantation. [2021]

6. China 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]. [2018]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Intravenous busulfan: in the conditioning treatment of pediatric patients prior to hematopoietic stem cell transplantation. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Busulfan concentration and graft rejection in pediatric patients undergoing hematopoietic stem cell transplantation. [2013]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Low-dose parenteral busulfan provides an extended window for the infusion of hematopoietic stem cells in murine hosts. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Reduced Toxicity Conditioning for Nonmalignant Hematopoietic Cell Transplants. [2021]

11. Netherlands pubmed.ncbi.nlm.nih.gov

A modified busulfan and cyclophosphamide preparative regimen for allogeneic transplantation in myeloid malignancies. [2018]

12. England 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. [2021]

13. Japan pubmed.ncbi.nlm.nih.gov

Graft-versus-host disease, the graft-versus-leukemia effect, and mixed chimerism following nonmyeloablative stem cell transplantation. [2019]