Stem Cell Transplantation for Leukemia

(ACCESS Trial)

Not currently recruiting at 40 trial locations

Overseen By Sarah Smith, RN, BSN

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Center for International Blood and Marrow Transplant Research

Disqualifiers: Prior allogeneic transplant, Pregnancy, 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: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of stem cell transplants from partially matched donors for individuals with blood cancers like leukemia and myelodysplastic syndromes. It employs various combinations of treatment drugs and radiation to help the body accept the new stem cells and prevent complications. The trial seeks participants with specific types of leukemia or lymphoma who are in remission or have controlled disease and lack a fully matched donor. Participants must tolerate chemotherapy and radiation as part of the treatment. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor to get specific guidance based on your situation.

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

Research has shown that treatments like those in this trial have generally been well-tolerated in past studies. Specifically, studies found that using fludarabine and busulfan before a peripheral blood stem cell (PBSC) transplant effectively controls cancer growth and is well-tolerated by patients. Side effects were manageable, and the overall safety was good.

The combination of fludarabine and total body irradiation (TBI) before a PBSC transplant also showed promising results. Studies reported low rates of complications, such as infections and severe graft-versus-host disease (GVHD), a condition where the donated cells attack the recipient’s body. Using fludarabine and melphalan for PBSC transplants improved disease control while maintaining a good safety profile.

For the treatment using fludarabine, cyclophosphamide, and TBI before a PBSC transplant, research suggests it is well-tolerated. While some side effects may occur, they are considered manageable. Similarly, the combination of busulfan and cyclophosphamide for bone marrow transplants has shown good safety results, with no transplant-related deaths in some studies.

Lastly, the combination of cyclophosphamide and TBI for bone marrow transplants showed favorable outcomes, with studies reporting good survival rates and manageable side effects.

This trial is in Phase 2, indicating that the treatment has passed initial safety tests in early trials. This phase focuses more on the treatment's effectiveness, but safety is still closely monitored. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for leukemia because they explore different conditioning regimens and stem cell sources to improve patient outcomes. Unlike traditional approaches that often rely on fully matched donors, these treatments use peripheral blood stem cell (PBSC) or bone marrow (BM) grafts from mismatched unrelated donors, potentially expanding donor availability. Additionally, these regimens include a variety of conditioning treatments, such as total body irradiation (TBI) and different combinations of chemotherapy drugs like fludarabine, busulfan, and melphalan, which may offer more personalized and potentially less toxic preparation for transplantation. By experimenting with these diverse regimens, the treatments aim to enhance engraftment success and reduce the risk of complications, providing new hope for patients with leukemia.

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

Research has shown that certain drug combinations for stem cell transplants can help reduce the risk of leukemia recurrence. In this trial, participants will receive different treatment regimens. One regimen uses fludarabine and busulfan, which studies have shown to improve survival rates without relapse for up to four years. Another regimen combines fludarabine with total body irradiation (TBI), a combination that has been well tolerated and effective, especially for patients in their first complete remission. The combination of fludarabine and melphalan, tested in another regimen, has effectively controlled the disease with manageable side effects. Additionally, using fludarabine with cyclophosphamide and TBI has resulted in high remission rates, with over 80% of patients achieving remission in some cases. Finally, the combination of busulfan and cyclophosphamide, part of another regimen, has been linked to better survival without leukemia and overall survival compared to other treatments. Each of these treatment combinations in this trial shows promise in improving outcomes for patients with blood cancers. ^{3 5 6 7 8}

Who Is on the Research Team?

Steven Devine, MD

Principal Investigator

NMDP/Be The Match

Are You a Good Fit for This Trial?

Adults aged 18-66 with various types of leukemia or lymphoma, fit for stem cell transplant using cells from a partially matched unrelated donor. They must have good heart, kidney, and lung function, an acceptable performance status score indicating they can carry out daily activities, and no severe infections or recent transplants. Pregnant women and those unable to consent are excluded.

Inclusion Criteria

I agree to donate stem cells or bone marrow.

My physical ability score is 70% or higher.

I am planned to receive a high-dose chemotherapy regimen.

Exclusion Criteria

I had a stem cell transplant using my own cells within the last 3 months.

Strata 1, 2 and 3 Recipient: Subject unwilling or unable to give informed consent, or unable to comply with the protocol including required follow-up and testing

I am not pregnant or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning and Transplantation

Participants receive conditioning regimens followed by hematopoietic cell transplantation from mismatched unrelated donors

7-10 days

Daily visits for conditioning and transplantation

Post-Transplantation Treatment

Post-transplant cyclophosphamide, tacrolimus, and mycophenolate mofetil are administered for GVHD prophylaxis

Approximately 2 weeks

Frequent monitoring visits

Follow-up

Participants are monitored for safety, effectiveness, and recovery post-transplantation

1 year

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Bone Marrow Hematopoietic Stem Cell Transplantation
• Cyclophosphamide
• Fludarabine
• Mycophenolate Mofetil
• PBSC Hematopoietic Stem Cell Transplantation (HSCT)
• Tacrolimus
• Total-body irradiation

Trial Overview The trial is testing hematopoietic cell transplantation (HCT) from HLA-mismatched unrelated donors in adults (using peripheral blood stem cells) and children (using bone marrow). It aims to prevent graft versus host disease using post-transplant cyclophosphamide along with other medications.

How Is the Trial Designed?

Group I: Regimen G (MAC: Cyclophosphamide and TBI; BM HCT) Experimental Treatment 8 Interventions

Patients receive: * Cyclophosphamide (100 mg/kg total dose) IV on days -5 and -4 * TBI (1200 cGy total dose) on days -3, -2 and -1 Patients receive a BM graft infusion from a mismatched unrelated donor on Day 0.

Group II: Regimen F (MAC: Busulfan and Cyclophosphamide; BM HCT) Experimental Treatment 8 Interventions

Patients receive: * Busulfan (dosed by age and weight per institutional standards to target goal pharmacokinetic (PK) in range noted in protocol.) on days -6 to -3 * Cyclophosphamide (100 mg/kg total dose) IV on days -2 and -1 Patients receive a bone marrow (BM) graft infusion from a mismatched unrelated donor on Day 0.

Group III: Regimen E (NMA: Fludarabine, Cyclophosphamide, TBI; PBSC HCT) Experimental Treatment 9 Interventions

Patients receive: * Fludarabine (150 mg/m2 total dose) IV on days -6 to -2 * Cyclophosphamide (29-50 mg/kg) IV on days -6 and -5 * TBI (200 cGy) on day -1 Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.

Group IV: Regimen D (RIC: Fludarabine and Melphalan; PBSC HCT) Experimental Treatment 8 Interventions

Patients receive: * Fludarabine (120-180 mg/m2 total dose) IV on days -7 to -3 * Melphalan (100-140 mg/m2) IV on day -1 Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.

Group V: Regimen C (RIC: Fludarabine and Busulfan; PBSC HCT) Experimental Treatment 8 Interventions

Patients receive: * Fludarabine (120-180 mg/m2 total dose) IV on days -6 to -2 * Busulfan (less than or equal to 8 mg/kg PO or 6.4 mg/kg IV) on days -5 and -4 Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.

Group VI: Regimen B (MAC: Fludarabine and TBI; PBSC HCT) Experimental Treatment 8 Interventions

Patients receive: * Fludarabine (90 mg/m2 total dose) IV on days -7 to -5 * Total body irradiation (TBI) (1200 cGy total dose) on days -4 to -1 Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.

Group VII: Regimen A (MAC: busulfan and fludarabine, PBSC HCT) Experimental Treatment 8 Interventions

Patients receive: * Busulfan (≥ 9 mg/kg total dose) IV or PO on days -6 to -3 * Fludarabine (150 mg/m2 total dose) IV on days -6 to -2 Patients receive a peripheral blood stem cell (PBSC) graft infusion from a mismatched unrelated donor on Day 0.

Who Is Running the Clinical Trial?

Center for International Blood and Marrow Transplant Research

Lead Sponsor

Trials

40

Recruited

200,190,000+

National Marrow Donor Program

Collaborator

Trials

63

Recruited

202,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31628924/

Comparative effectiveness of busulfan/cyclophosphamide ... Amongst AML patients, those receiving Bu/Flu had more rapid neutrophil and platelet recovery and a shorter length of hospital stay (LOS); there were no ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3169009/

Comparative Analysis of Busulfan and Cyclophosphamide ... In this large cohort analysis of CIBMTR registry data, we conclude that Cy/TBI and BuCy regimens result in similar clinical outcome in URD transplant recipient ...

3. nature.com nature.com/articles/s41408-024-01116-5

long term analysis of GITMO AML-R2 trial We report the long-term results of a randomized trial (GITMO, AML-R2), comparing 1:1 the combination of busulfan and cyclophosphamide (BuCy2, n = 125)

4. ashpublications.org ashpublications.org/blood/article/122/24/3863/31939/Better-leukemia-free-and-overall-survival-in-AML

Better leukemia-free and overall survival in AML in first ... Key Points. In combination with cyclophosphamide, intravenous busulfan is associated with better leukemia-free and overall survival in AML than TBI.

5. journals.lww.com journals.lww.com/hosct/fulltext/2020/13030/comparative_effectiveness_of.6.aspx

Comparative effectiveness of busulfan/cyclophosphamide... Amongst AML patients, those receiving Bu/Flu had more rapid neutrophil and platelet recovery and a shorter length of hospital stay (LOS); there were no ...

6. ashpublications.org ashpublications.org/bloodadvances/article/7/18/5225/496607/Association-between-busulfan-exposure-and-survival

Association between busulfan exposure and survival in ... Busulfan exposure is associated with OS; 5-year survival with an exposure of ≥59.5 vs <59.5 mg × h/L was 67% (95% CI, 59-76) vs 40%.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9936063/

Safety and efficacy of a modified busulfan/cyclophosphamide ... No transplantation-related deaths were recorded. One patient who relapsed after auto-HSCT and did not achieve remission with combination chemotherapy died at ...

8. astctjournal.org astctjournal.org/article/S1083-8791(02)50009-4/pdf

Evaluation of Safety and Pharmacokinetics of Although further study for long-term efficacy is warranted, IV BU can be given safely with reproducible results on a twice-daily divided or single-daily dosing.