Bone Marrow Transplant for Leukemia

Recruiting at 8 trial locations

Overseen By Preethi Prasad, MSc.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Ossium Health, Inc.

Must not be taking: Investigational drugs

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

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and feasibility of using bone marrow transplants from deceased donors to treat certain blood cancers, such as leukemia, myelodysplastic syndrome, and some lymphomas. Participants will receive one of several pre-transplant conditioning treatments to prepare for the transplant. Those with a type of leukemia or lymphoma that has responded to chemotherapy or radiation and lack a living donor match might find this trial suitable. Researchers will monitor participants closely for safety over 56 days, with follow-ups continuing for a year. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

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.

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

Research has shown that bone marrow transplants, also known as allogeneic stem cell transplants, have generally been well-tolerated in past studies. For example, one study found that the risk of dying from non-cancer-related causes within the first year was about 9.5% in recent years, a significant improvement from the 1990s rate of 24.4%.

However, bone marrow transplants are serious procedures and carry risks. The chance of dying within the first two years after the transplant, known as early mortality, can range from 10% to 30%, depending on factors such as the patient's health and specific treatment plan.

Overall, while bone marrow transplants involve risks, past data show that safety has improved over time, with fewer serious outcomes than before. Prospective participants should discuss any concerns with healthcare providers when considering joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this bone marrow transplant treatment for leukemia because it utilizes Ossium HPC, Marrow, which is a novel approach to stem cell transplantation. Unlike traditional methods, which often rely on bone marrow or peripheral blood stem cells from related or unrelated donors, this treatment uses a unique source of hematopoietic progenitor cells (HPC) from Ossium. This could potentially lead to better engraftment rates and reduce complications. Additionally, the combination of pre-transplant conditioning regimens, including Total Body Irradiation and various chemotherapeutic agents like Fludarabine and Busulfan, offers a flexible approach tailored to the patient's needs, possibly improving outcomes and minimizing side effects.

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

Research has shown that bone marrow transplants can effectively treat leukemia. This trial will evaluate the effectiveness of bone marrow transplants using different pre-transplant conditioning regimens. Studies have found that transplants work better against leukemia than chemotherapy. In past research, patients with certain types of leukemia lived longer after receiving a bone marrow transplant. For example, some studies found that bone marrow transplants might cure patients with acute leukemia. While risks are associated with the transplant, previous data clearly demonstrate the benefits of this treatment in fighting leukemia. ^{6 7 8 9 10}

Who Is on the Research Team?

Jeffery Auletta, MD

Principal Investigator

Center for International Blood and Marrow Transplant Research

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Bone Marrow Transplant
• Busulfan
• Cyclophosphamide
• Filgrastim
• Fludarabine
• Mycophenolate Mofetil
• Tacrolimus
• Total Body Irradiation

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.

How Is the Trial Designed?

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 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?

Ossium Health, Inc.

Lead Sponsor

Trials

11

Recruited

200+

Center for International Blood and Marrow Transplant Research

Collaborator

Trials

40

Recruited

200,190,000+

Published Research Related to This Trial

Allogeneic bone marrow transplantation is an effective treatment for acute leukemia, leading to increased long-term survival and potential cures, but it requires an HLA-identical donor.

To address the challenge of finding suitable donors, large international registries of HLA-typed volunteer marrow donors have been created, and new research is exploring advanced techniques like stem cell purification and new immunosuppressive agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

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]

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]

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]

Allogeneic hematopoietic stem cell transplantation (HSCT) is a crucial treatment option for children and adolescents with high-risk acute leukemia and certain genetic diseases, utilizing various stem cell sources such as bone marrow, peripheral blood stem cells, and umbilical cord blood.

The choice of stem cell source depends on factors like availability, HLA compatibility, and urgency, with each source presenting unique risks and benefits that must be carefully considered for optimal patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stem cell source and outcome after hematopoietic stem cell transplantation (HSCT) in children and adolescents with acute leukemia. Peters, C., Cornish, JM., Parikh, SH., et al.[2010]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/9164184/

Results of allogeneic bone marrow transplants for leukemia ... Results: Transplant-related mortality was significantly higher after alternative donor transplants than after HLA-identical sibling transplants. Among patients ...

2. astctjournal.org astctjournal.org/article/S2666-6367(21)00634-5/fulltext

Feasibility and Outcomes of a Third Allogeneic ... Hence, cumulative incidence of NRM was 36% (95% CI, 22% to 50%), 42% (95% CI, 27% to 56%), and 47% (95% CI, 31% to 61%) at 6 months, 1 year, and 2 years (Figure ...

3. nature.com nature.com/articles/s41598-025-05602-z

Clinical outcomes of allogeneic hematopoietic stem cell ... The 3-year OS rates for MRD-positive and MRD-negative groups were 72.91% and 88.66%, respectively, without significant difference (p = 0.316) ( ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0006497120676728

Bone Marrow Transplants May Cure Patients With Acute ... Superiority of transplants over chemotherapy is related to improved antileukemia efficacy. One hundred thirteen of 115 evaluable (surviving ≥ 21 days with ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6395335/

Haploidentical versus unrelated allogeneic stem cell ... Allogeneic stem cell transplantation may rescue about 25% of acute myeloid leukemia patients with active disease. Importantly, the outcomes of transplants from ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2531137925001555

OUTCOMES OF ALLOGENEIC STEM CELL ... This study presents data on allogeneic HSCT procedures performed in our transplant center for AML patients.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6717573/

Long-term outcome after allogeneic hematopoietic cell ... Early mortality (within 2 years) after transplantation is known to be 10-30%, but so far no study has analyzed the outcome of transplanted MF patients after ...

8. ashpublications.org ashpublications.org/bloodadvances/article/4/24/6283/474704/How-much-has-allogeneic-stem-cell-transplant

How much has allogeneic stem cell transplant–related ... In the matched-pairs analysis of 3718 patients in each group, nonrelapse mortality at 1 year was 24.4% in the 1990s and 9.5% from 2013 through ...

9. cancer.org cancer.org/cancer/managing-cancer/treatment-types/stem-cell-transplant/types-of-transplants.html

Types of Stem Cell or Bone Marrow Transplant Because this treatment involves 2 transplants, the risk of serious outcomes is higher than for a single transplant. Sometimes, an auto ...

10. mayo.edu mayo.edu/research/clinical-trials/tests-procedures/bone-marrow-transplant

Bone Marrow Transplant Clinical Trials The purpose of the study is to determine if overall mortality is affected one year after a hematopoietic stem cell transplant (HCT) in patients given a vaccine ...