Stem Cell Transplantation for Blood Cancers

Recruiting in Palo Alto (17 mi)

Overseen by Margaret MacMillan, MD

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Masonic Cancer Center, University of Minnesota

Disqualifiers: Pregnant, HIV, Hepatitis B/C, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This is a phase II, open-label, prospective study of T cell receptor alpha/beta depletion (α/β TCD) peripheral blood stem cell (PBSC) transplantation for children and adults with hematological malignancies

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.

What data supports the effectiveness of the drug combination used in the Stem Cell Transplantation for Blood Cancers trial?

Research shows that adding melphalan to fludarabine and busulfan improves survival rates in patients undergoing stem cell transplantation for blood cancers. Specifically, a study found that this combination led to better 5-year overall survival and lower relapse rates compared to using fludarabine and busulfan alone. ^{1 2 3 4 5}

Is stem cell transplantation using busulfan, fludarabine, and melphalan safe for humans?

Research shows that using busulfan, fludarabine, and melphalan in stem cell transplantation is generally well-tolerated in humans. Studies indicate that these drugs, when used together, have an acceptable safety profile with fewer side effects compared to some other drug combinations, and they are effective in treating certain blood cancers. ^{2 5 6 7 8}

What makes the stem cell transplantation treatment with Busulfan, Fludarabine, and Melphalan unique for blood cancers?

This treatment is unique because it combines fludarabine and busulfan with melphalan to enhance the anti-leukemic effect and achieve rapid donor cell integration, which is particularly beneficial for patients with advanced myeloid malignancies. It also shows less toxicity compared to traditional regimens, leading to better survival rates and fewer complications. ^{5 6 8 9 10}

Research Team

Margaret MacMillan, MD

Principal Investigator

University of Minnesota Masonic Cancer Center

Eligibility Criteria

This trial is for children and adults up to 60 years old with various blood cancers, including leukemia and myelodysplasia. Participants must have confirmed hematological malignancies, be in a specific health condition (Karnofsky performance status ≥ 70% or Lansky play score ≥ 50%), and have adequate organ function. Pregnant individuals, those with active infections or known HIV/Hepatitis B/C, prior transplants, CML blast crisis, or CNS malignancy cannot join.

Inclusion Criteria

I am 60 years old or younger.

My leukemia is considered low risk based on specific criteria.

I have been diagnosed with Acute Myeloid Leukemia or a related condition.

Exclusion Criteria

I have an active brain or spinal cord tumor.

Pregnant or breastfeeding

My condition is in the blast phase of chronic myeloid leukemia.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive T cell receptor alpha/beta depletion (α/β TCD) peripheral blood stem cell transplantation

6 weeks

Multiple visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including GVHD incidence and engraftment

12 months

Regular follow-up visits

Long-term follow-up

Participants are monitored for overall survival and non-relapse mortality

85 months

Treatment Details

Interventions

• Busulfan (Alkylating agents)
• Fludarabine (Anti-metabolites)
• Levetiracetam (Other)
• Melphalan (Alkylating agents)
• Rituximab (Monoclonal Antibodies)

Trial Overview The study tests T cell receptor alpha/beta depletion PBSC transplantation using drugs like Fludarabine, Busulfan, Melphalan, Rituximab & Levetiracetam on patients with blood cancers. It's an open-label phase II trial aiming to see how well this treatment works for these conditions.

Participant Groups

Group I: Fludarabine (flu), Total Body Irradiation (TBI), Flu/TBI Regimen Experimental Treatment 2 Interventions

Patients will be treated on the most medically appropriate regimen with a preference for Flu/TBI Arm followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells.

Group II: Fludarabine (flu), Busulfan (bu), Melphalan (Mel) Regimen for Pediatric Patients Only Experimental Treatment 5 Interventions

Flu/Bu/Mel will the preference for patients with JMML or infants with leukemia.

Group III: Fludarabine (flu), Busulfan (bu), Flu/Bu Regimen Experimental Treatment 4 Interventions

Patients will be treated on the most medically appropriate regimen with a preference for Flu/TBI Arm followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells.

Busulfan is already approved in Canada, Japan for the following indications:

Approved in Canada as Busulfex for:

• Chronic myeloid leukemia
• Acute myeloid leukemia
• Bone marrow transplantation conditioning

Approved in Japan as Busulfan for:

• Chronic myeloid leukemia
• Acute myeloid leukemia
• Bone marrow transplantation conditioning

Who Is Running the Clinical Trial?

Masonic Cancer Center, University of Minnesota

Lead Sponsor

Trials

285

Recruited

15,700+

Dr. Melissa A. Geller

Masonic Cancer Center, University of Minnesota

Chief Medical Officer since 2022

MD from University of Minnesota

Dr. Jeffrey Miller

Masonic Cancer Center, University of Minnesota

Chief Executive Officer

MD from University of Minnesota

Findings from Research

In a study of 846 patients who underwent allogeneic hematopoietic stem cell transplantation, adding melphalan to the Flu/Bu4 regimen improved 5-year overall survival rates, with 34.2% survival in the Flu/Bu4/Mel group compared to 30.1% in the Flu/Bu4 group.

The addition of melphalan was linked to a lower incidence of relapse and relapse-associated mortality, indicating that it enhances the effectiveness of the treatment without increasing non-relapse mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adding melphalan to fludarabine and a myeloablative dose of busulfan improved survival after allogeneic hematopoietic stem cell transplantation in a propensity score-matched cohort of hematological malignancies. Shimomura, Y., Hara, M., Yamamoto, H., et al.[2021]

The study compared outcomes of 67 patients treated with intravenous busulfan-cyclophosphamide to 148 patients treated with busulfan-fludarabine before allogeneic stem cell transplantation, finding that the busulfan-fludarabine regimen resulted in significantly improved safety and recovery from side effects.

Patients receiving the busulfan-fludarabine treatment had extremely low one-year treatment-related mortality and high overall and event-free survival rates, suggesting that this regimen may be a better option than conventional chemotherapy for those in first complete remission of acute myeloid leukemia or myelodysplastic syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced-toxicity conditioning therapy with allogeneic stem cell transplantation for acute leukemia. Andersson, BS., de Lima, M., Thall, PF., et al.[2021]

The FLU/BU4/MEL conditioning regimen, which includes fludarabine, busulfan, and melphalan, demonstrated curative potential in patients with advanced myeloid malignancies, achieving complete chimerism within one month after transplantation.

In a study of 42 patients, the 4-year overall survival rate was 66.0% and the disease-free survival rate was 59.5%, indicating that this regimen is effective even for those who were not in complete remission at the time of transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addition of melphalan to fludarabine/busulfan (FLU/BU4/MEL) provides survival benefit for patients with myeloid malignancy following allogeneic bone-marrow transplantation/peripheral blood stem-cell transplantation. Ueda, T., Maeda, T., Kusakabe, S., et al.[2020]

In a study of 30 adult patients undergoing allogeneic hematopoietic stem cell transplant, fludarabine combined with full-dose busulfan (FluBu) and fludarabine with melphalan (FluMel) showed similar levels of hematological toxicity, indicating that both regimens are comparably safe.

The timing and duration of severe neutropenia were similar between the two groups, with both regimens resulting in a comparable recovery time for neutrophils and platelets post-transplant, suggesting that FluBu can be an effective alternative to standard reduced intensity conditioning regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparable kinetics of myeloablation between fludarabine/full-dose busulfan and fludarabine/melphalan conditioning regimens in allogeneic peripheral blood stem cell transplantation. Chunduri, S., Dobogai, LC., Peace, D., et al.[2013]

A conditioning regimen of busulfan, fludarabine, and melphalan was safely administered to 6 patients aged 1 to 19 years with very high-risk myeloid malignancies, resulting in complete donor engraftment even with small umbilical cord blood grafts.

All patients remained in remission without experiencing acute or chronic graft-versus-host disease during a median follow-up of 24 months, suggesting strong disease control and safety of this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alternative Donor Hematopoietic Cell Transplantation Conditioned With Myeloablative Busulfan, Fludarabine, and Melphalan is Well Tolerated and Effective Against High-risk Myeloid Malignancies. Katsanis, E., Sapp, LN., Pelayo-Katsanis, L., et al.[2022]

In a study comparing two treatment regimens for children undergoing hematopoietic cell transplantation, the combination of fludarabine and busulfan (FluBu) showed similar survival rates to busulfan and cyclophosphamide (BuCy), with 2-year survival rates of 82% for FluBu and 78% for BuCy.

The FluBu regimen was associated with significantly lower toxicity, including reduced rates of lung injury, veno-occlusive disease, and infections, as well as a shorter duration of neutropenia, indicating it may be a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fludarabine and exposure-targeted busulfan compares favorably with busulfan/cyclophosphamide-based regimens in pediatric hematopoietic cell transplantation: maintaining efficacy with less toxicity. Bartelink, IH., van Reij, EM., Gerhardt, CE., et al.[2014]

In a study of 32 patients with acute myeloid leukemia in first complete remission, the busulfan/fludarabine (Bu/Flu) conditioning regimen resulted in significantly lower transplant-related toxicity compared to the busulfan/cyclophosphamide (Bu/Cy) regimen, with a lower incidence of severe side effects (68.8% vs. 25.0%).

Both regimens showed similar efficacy in terms of overall survival and event-free survival rates, indicating that Bu/Flu is a safer option without compromising treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A comparison of toxicity and efficacy between busulfan plus fludarabine and busulfan plus cyclophosphamide for allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia]. Liu, H., Fan, ZP., Jiang, QL., et al.[2014]

In a study of 394 acute myeloid leukemia patients undergoing allogeneic stem cell transplantation, the fludarabine plus melphalan (FM) regimen showed a significantly lower relapse incidence compared to fludarabine plus busulfan (FB), indicating better control of the disease.

Despite the differences in relapse rates, both FM and FB regimens resulted in similar overall survival rates, suggesting that while FM may be more effective in preventing relapse, both treatments are comparably effective in terms of long-term survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced-intensity conditioning with fludarabine and busulfan versus fludarabine and melphalan for patients with acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Baron, F., Labopin, M., Peniket, A., et al.[2015]

References

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

Adding melphalan to fludarabine and a myeloablative dose of busulfan improved survival after allogeneic hematopoietic stem cell transplantation in a propensity score-matched cohort of hematological malignancies. [2021]

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

Myeloablative busulfan/cytoxan conditioning versus reduced-intensity fludarabine/melphalan conditioning for allogeneic hematopoietic stem cell transplant in patients with acute myelogenous leukemia. [2019]

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

Reduced-toxicity conditioning therapy with allogeneic stem cell transplantation for acute leukemia. [2021]

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

Choosing a Reduced-Intensity Conditioning Regimen for Allogeneic Stem Cell Transplantation, Fludarabine/Busulfan versus Fludarabine Melphalan: A Systematic Review and Meta-Analysis. [2020]

5. Japan pubmed.ncbi.nlm.nih.gov

Addition of melphalan to fludarabine/busulfan (FLU/BU4/MEL) provides survival benefit for patients with myeloid malignancy following allogeneic bone-marrow transplantation/peripheral blood stem-cell transplantation. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Comparable kinetics of myeloablation between fludarabine/full-dose busulfan and fludarabine/melphalan conditioning regimens in allogeneic peripheral blood stem cell transplantation. [2013]

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

Alternative Donor Hematopoietic Cell Transplantation Conditioned With Myeloablative Busulfan, Fludarabine, and Melphalan is Well Tolerated and Effective Against High-risk Myeloid Malignancies. [2022]

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

Fludarabine and exposure-targeted busulfan compares favorably with busulfan/cyclophosphamide-based regimens in pediatric hematopoietic cell transplantation: maintaining efficacy with less toxicity. [2014]

9. China pubmed.ncbi.nlm.nih.gov

[A comparison of toxicity and efficacy between busulfan plus fludarabine and busulfan plus cyclophosphamide for allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia]. [2014]

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

Reduced-intensity conditioning with fludarabine and busulfan versus fludarabine and melphalan for patients with acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation. [2015]