Bone Marrow Transplant for Leukemia

Recruiting at 8 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Ossium Health, Inc.

Must not be taking: Investigational drugs

Disqualifiers: Living donor, Prior HCT, Pregnancy, Infections, others

No Placebo Group

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing the safety of using bone marrow from a deceased donor to treat patients with severe leukemia. The goal is to see if this new bone marrow can help produce healthy blood cells. Patients will be monitored closely for any side effects and overall effectiveness over several months.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on an investigational drug for your condition, you must stop it at least 5 half-lives before starting the trial.

What data supports the effectiveness of the treatment Bone Marrow Transplant for Leukemia?

Research shows that allogeneic bone marrow transplantation is an effective treatment for leukemia, with increased long-term survival and potential cure rates, especially when an HLA-identical donor is available. Additionally, donor leukocyte transfusions after transplantation have induced lasting remissions in many patients with chronic myelogenous leukemia and other types of leukemia. ^{1 2 3 4 5}

Is bone marrow transplant generally safe for humans?

Bone marrow transplants can be effective for treating leukemia and other blood diseases, but they come with risks such as graft failure, graft-versus-host disease (where the donor cells attack the recipient's body), and infections. These risks can be higher when the donor is not a perfect match, but improvements in treatment are helping to reduce complications. ^{3 5 6 7 8}

How is the bone marrow transplant treatment for leukemia different from other treatments?

Bone marrow transplant for leukemia is unique because it involves infusing healthy bone marrow from a donor to replace the patient's diseased marrow, offering a potential cure. This treatment requires a matching donor, often a sibling, and involves high-dose chemotherapy and sometimes radiation to prepare the patient, which is different from standard chemotherapy or radiation treatments alone. ^{5 9 10 11 12}

Research Team

Jeffery Auletta, MD

Principal Investigator

Center for International Blood and Marrow Transplant Research

Eligibility Criteria

This trial is for adults aged 18-55 (or up to 70 for a specific regimen) with certain types of acute leukemia in remission, who need a bone marrow transplant and match the donor's tissue type at least half-way. They must be able to consent, have decent heart function and overall health status, and commit to study procedures for one year.

Inclusion Criteria

I am mostly able to care for myself but may need help.

My heart's pumping ability is within the required range.

I am willing and able to follow all study rules and attend all appointments.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-transplant Conditioning

Patients receive myeloablative or reduced intensity conditioning regimen prior to the transplant

1-2 weeks

Transplantation

Bone marrow transplant with Ossium HPC, Marrow

1 day

Post-Transplant Treatment

Post-transplant treatment with Cyclophosphamide, Tacrolimus, Mycophenolate Mofetil, and Filgrastim

56 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Treatment Details

Interventions

• Bone Marrow Transplant (Bone Marrow Transplant)
• Busulfan (Chemotherapy)
• Cyclophosphamide (Chemotherapy)
• Filgrastim (Hematopoietic Growth Factor)
• Fludarabine (Chemotherapy)
• Mycophenolate Mofetil (Immunosuppressant)
• Tacrolimus (Immunosuppressant)
• Total Body Irradiation (Radiation Therapy)

Trial Overview The study tests the safety of bone marrow transplants from deceased donors in patients with blood cancers. It compares two pre-transplant conditioning regimens: myeloablative (stronger) or reduced intensity (milder), followed by close monitoring for nearly two months post-transplant.

Participant Groups

Group I: Cohort 2 Experimental Treatment 4 Interventions

\*Open to enrollment after DSMB review of Cohort 1 safety events through Day 56\* Bone Marrow Transplant with Ossium HPC, Marrow Pre-transplant conditioning treatment with: Regimen A(MAC): Busulfan and Fludarabine \[OR\] Regimen B(MAC): Fludarabine and Total Body Irradiation \[OR\] Regimen C(RIC): Fludarabine, Cyclophosphamide, and Total Body Irradiation \[OR\] Regimen D(RIC): Fludarabine, Melphalan, and Total Body Irradiation Post-Transplant treatment with Cyclophosphamide, Tacrolimus, Mycophenolate Mofetil, and Filgrastim

Group II: Cohort 1 Experimental Treatment 4 Interventions

Bone Marrow Transplant with Ossium HPC, Marrow Pre-transplant myeloablative conditioning treatment with: Regimen A(MAC): Busulfan and Fludarabine \[OR\] Regimen B(MAC): Fludarabine and Total Body Irradiation \[OR\] Regimen C(RIC): Fludarabine, Cyclophosphamide, and Total Body Irradiation \[OR\] Regimen D (RIC): Fludarabine, Melphalan, and Total Body Irradiation Post-Transplant treatment with Cyclophosphamide, Tacrolimus, Mycophenolate Mofetil, and Filgrastim

Bone Marrow Transplant is already approved in Canada, Japan for the following indications:

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?

Ossium Health, Inc.

Lead Sponsor

Trials

11

Recruited

200+

Center for International Blood and Marrow Transplant Research

Collaborator

Trials

40

Recruited

200,190,000+

Findings from Research

In a study of 25 patients with acute myeloid leukemia, the busulfan and melphalan conditioning regimen resulted in a 48% overall survival rate after 36 months, indicating its effectiveness for patients in first complete remission.

Factors such as intensive consolidation with high-dose arabinoside and the presence of grade II acute graft-versus-host disease were associated with improved survival outcomes, highlighting the importance of treatment strategies in enhancing patient prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Busulfan and melphalan as conditioning regimen for allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia in first complete remission. Bueno, ND., Dulley, FL., Saboya, R., et al.[2021]

Allogeneic bone marrow transplantation is an effective treatment for leukemia, with donor T-cells and intensive chemotherapy/radiotherapy playing crucial roles in controlling the disease.

Transfusion of donor leukocytes (DLT) after transplantation can lead to lasting remissions in many patients with chronic myelogenous leukemia (CML) and other blood cancers, especially when administered two months post-transplant to avoid graft-versus-host disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Donor leukocyte transfusions for treatment of leukemic relapse after bone marrow transplantation. EBMT Immunology and Chronic Leukemia Working Parties. Kolb, HJ.[2019]

Allogeneic bone marrow transplantation often requires alternative donors, such as haploidentical relatives or unrelated donors, due to the lack of HLA-identical siblings, which increases risks like graft failure and graft-versus-host disease compared to matched sibling donors.

Despite these risks, some studies suggest that alternative donor transplants may not lead to worse disease-free survival, potentially due to a beneficial graft-versus-leukemia effect, especially when performed earlier in the disease course.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mismatched bone marrow transplantation. Henslee-Downey, PJ.[2019]

All 15 leukemia patients who received allogeneic bone marrow transplantation (Allo-BMT) from HLA haplotype matched related donors successfully established engraftment, with median recovery times for granulocytes and platelets of 19 and 21 days, respectively.

While 33.3% of patients experienced acute graft-versus-host disease (GVHD), the combination of G-CSF stimulation for donors and a comprehensive GVHD prophylaxis program showed promise in managing complications, with 9 out of 15 patients remaining disease-free after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Preliminary study of HLA haplotype matched and T-cell undepleted allogeneic bone marrow transplantation for treatment of leukemia]. Ji, S., Chen, H., Wang, H.[2006]

Allogeneic bone marrow transplants are an effective treatment for various hematologic diseases, including leukemia and aplastic anemia, with over 33,000 procedures performed between 1955 and 1990, particularly increasing in the late 1980s.

Recent advancements have allowed for successful transplants using unrelated or partially matched donors, although complications like graft failure and graft versus host disease remain significant challenges that can be predicted through risk factor assessment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current status of allogeneic bone marrow transplantation. Sobocinski, KA., Horowitz, MM., Rimm, AA., et al.[2019]

Bone marrow transplantation has shown success as an experimental therapy for conditions like aplastic anemia, severe combined immunodeficiency, and leukemia, indicating its potential efficacy in treating serious blood disorders.

The report discusses the transplantation procedure and highlights possible complications that may arise during the process, emphasizing the need for careful management and monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Bone marrow transplantation (author's transl)]. Neithammer, D., Bienzle, U., Kleihauer, E.[2006]

Bone marrow transplantation is a key treatment for severe aplastic anemia and acute leukemia, requiring an HLA-matched sibling donor, but does not require ABO blood type compatibility.

Survival rates after transplantation are 17% for acute leukemia and 40% for aplastic anemia, with significant complications including immune rejection and graft versus host disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Allogenic bone marrow grafts (author's transl)]. Gluckman, E., Marty, M., Boiron, M.[2021]

The study analyzed HLA typing in 434 unrelated individuals from Vojvodina, revealing that the likelihood of finding HLA identical or partially matched unrelated donors is higher among closely related populations, such as those from Crete, Romania, and Scotland.

The research indicates that the probability of finding compatible donors is influenced by HLA matching, phenotype frequencies, and the size of the donor pool, suggesting that these methods can help optimize donor searches for bone marrow and stem cell transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The probability of finding HLA identical or partially matched unrelated donors in the population of Vojvodina]. Vojvodić, S., Popović, S.[2019]

Allogeneic marrow transplantation from normal donors can be a life-saving treatment for various blood-related diseases, with successful outcomes primarily seen when using HLA-identical sibling donors.

Recent advancements, including the establishment of a National Marrow Donor Program, have improved the chances of finding HLA-identical unrelated donors, expanding the availability of marrow transplants for patients in need.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic marrow transplantation: the Seattle experience. Hansen, JA., Anasetti, C., Beatty, PG., et al.[2021]

Allogeneic bone marrow transplantation (BMT) is a critical treatment for various hematologic diseases, particularly severe aplastic anemia and certain leukemias, with the best outcomes seen in younger patients and those in remission.

While BMT can offer a chance for cure, it carries significant risks, including graft failure, graft-versus-host disease, and long-term complications, which may limit its use to specialized centers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic bone marrow transplantation in the treatment of hematologic diseases. Yee, GC., McGuire, TR.[2021]

References

1. Brazil pubmed.ncbi.nlm.nih.gov

Busulfan and melphalan as conditioning regimen for allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia in first complete remission. [2021]

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

Donor leukocyte transfusions for treatment of leukemic relapse after bone marrow transplantation. EBMT Immunology and Chronic Leukemia Working Parties. [2019]

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

Mismatched bone marrow transplantation. [2019]

4. China pubmed.ncbi.nlm.nih.gov

[Preliminary study of HLA haplotype matched and T-cell undepleted allogeneic bone marrow transplantation for treatment of leukemia]. [2006]

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

Allogeneic bone marrow transplantation in acute myeloid and lymphocytic leukemia. [2019]

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

Stem cell source and outcome after hematopoietic stem cell transplantation (HSCT) in children and adolescents with acute leukemia. [2010]

7. France pubmed.ncbi.nlm.nih.gov

Current status of allogeneic bone marrow transplantation. [2019]

8. Germany pubmed.ncbi.nlm.nih.gov

[Bone marrow transplantation (author's transl)]. [2006]

9. France pubmed.ncbi.nlm.nih.gov

[Allogenic bone marrow grafts (author's transl)]. [2021]

10. Serbia pubmed.ncbi.nlm.nih.gov

[The probability of finding HLA identical or partially matched unrelated donors in the population of Vojvodina]. [2019]

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

Allogeneic marrow transplantation: the Seattle experience. [2021]

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

Allogeneic bone marrow transplantation in the treatment of hematologic diseases. [2021]