Shortened Chemotherapy Before Stem Cell Transplant for Blood Cancers

Overseen By Roni Tamari, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

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

Compensation: Varies

Number of Visits: Unknown

39 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to see if a condensed version of the chemotherapy regimen busulfan, melphalan, fludarabine (bu/mel/flu) and the drug antithymocyte globulin (ATG-also referred to as rATG or thymoglobulin) can have the same or fewer number of severe side effects in people with various blood cancers 30 days after they receive an allogeneic hematopoietic cell transplantation.

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 treatment Shortened Chemotherapy Before Stem Cell Transplant for Blood Cancers?

Research shows that adding melphalan to a regimen of fludarabine and busulfan improves survival rates for patients with myeloid malignancies undergoing stem cell transplants. This combination helps achieve rapid complete chimerism, which is crucial for successful transplantation. ^{1 2 3 4 5}

Is the shortened chemotherapy before stem cell transplant generally safe for humans?

Research indicates that the combination of fludarabine, busulfan, and melphalan used in stem cell transplants is associated with reduced toxicity and improved safety, showing low treatment-related mortality and better survival rates in patients with blood cancers. ^{4 6 7 8 9}

How is the treatment of shortened chemotherapy before stem cell transplant for blood cancers different from other treatments?

This treatment uses a combination of drugs, including fludarabine, busulfan, and melphalan, which is designed to be less toxic while still effective, especially for high-risk blood cancers. It aims to improve survival and quality of life by achieving rapid donor cell integration and reducing the risk of relapse compared to traditional regimens. ^{1 4 5 6 10}

Research Team

Michael Scordo, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults with various blood cancers eligible for stem cell transplantation may join this trial. They should have specific types of leukemia, myeloma, or lymphoma responding to therapy, adequate organ function, and not be pregnant or breastfeeding. Those with active brain cancer, uncontrolled infections, recent autologous transplants (except certain myeloma cases), HIV/HTLV, or unwillingness to use contraception are excluded.

Inclusion Criteria

My AML is in the first complete remission and is not low risk.

I am 18 years old or older.

My condition is chronic myeloid leukemia (CML).

Exclusion Criteria

I had a stem cell transplant using my own cells less than 6 months ago, except if I have high-risk multiple myeloma.

Patient or guardian unable to give informed consent or unable to comply with the treatment protocol.

My cancer has spread outside the bone marrow.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy

Participants receive a condensed chemotherapy regimen of busulfan, melphalan, and fludarabine, along with antithymocyte globulin (ATG) for GVHD prophylaxis

7 days

Transplantation

Participants undergo allogeneic hematopoietic cell transplantation

1 day

Follow-up

Participants are monitored for safety and effectiveness, focusing on grade 4 toxicities, for 30 days post-transplantation

4 weeks

Treatment Details

Interventions

• Allogeneic hematopoietic cell transplantation (Allo-HCT)
• Antithymocyte globulin (ATG)
• Busulfan
• Fludarabine
• Melphalan

Trial Overview The study is testing a shortened chemotherapy regimen before allogeneic hematopoietic cell transplantation (Allo-HCT). It involves lower doses of busulfan combined with melphalan and fludarabine plus antithymocyte globulin (ATG) to see if it reduces severe side effects within 30 days post-transplant.

Participant Groups

Group I: patients with multiple myeloma Experimental Treatment 5 Interventions

A. Busulfan 0.8 mg/kg every 6 hours x 10 doses, with dose adjustments made according to PK levels. B. Melphalan (70 mg/m2/day) administered on days -6 and -5. C. Fludarabine (25 mg/m2/day) administered on days -6, -5, -4, -3, -2. All patients receiving matched related or unrelated donor allografts receive anti-thymocyte globulin (ATG) 2.5 mg/kg/day on days -3 and -2 to deplete chemotherapy resistant host T-cells that could hinder engraftment, and it may provide additional GVHD prophylaxis.

Group II: patients hematologic malignancies other than multiple myeloma Experimental Treatment 5 Interventions

A. Busulfan 3.2 mg/kg/day, with dose adjustments made according to pharmacokinetic (PK) levels. B. Melphalan (70mg/m2/day) administered on days -6 and -5. C. Fludarabine (25mg/m2/ day) administered on days -6, -5, -4, -3, and -2. All patients receiving matched related or unrelated donor allografts receive anti-thymocyte globulin (ATG) 2.5 mg/kg/day on days -3 and -2 to deplete chemotherapy resistant host T-cells that could hinder engraftment, and it may provide additional GVHD prophylaxis.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Findings from Research

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]

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 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]

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]

In a study of 54 adults undergoing matched related donor blood cell transplantation, pretransplantation anti-thymocyte globulin (ATG) significantly reduced the incidence of chronic graft-versus-host disease (cGVHD) from 96% in the control group to 55% in the ATG group, indicating improved safety and potential quality of life for survivors.

Patients receiving ATG also experienced lower non-relapse mortality rates at 100 days (4% vs. 17%) and at 4 years (9% vs. 34%), suggesting that ATG may enhance overall survival despite a trend towards higher relapse rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adult recipients of matched related donor blood cell transplants given myeloablative regimens including pretransplant antithymocyte globulin have lower mortality related to graft-versus-host disease: a matched pair analysis. Russell, JA., Turner, AR., Larratt, L., et al.[2013]

In a study of 95 patients undergoing allogeneic stem cell transplantation, replacing cyclophosphamide with fludarabine in the conditioning regimen (busulfan+fludarabine) led to faster engraftment and significantly lower rates of acute and chronic graft-versus-host disease (GVHD).

The fludarabine regimen also resulted in better event-free survival and overall survival rates compared to the standard busulfan and cyclophosphamide regimen, indicating it may be a more effective option for myeloablative conditioning in allogeneic SCT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New myeloablative conditioning regimen with fludarabine and busulfan for allogeneic stem cell transplantation: comparison with BuCy2. Chae, YS., Sohn, SK., Kim, JG., et al.[2022]

References

1. 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]

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

Busulfan in hematopoietic stem cell transplantation. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Reduced-intensity conditioning with busulfan and fludarabine with or without antithymocyte globulin in HLA-identical sibling transplantation--a retrospective analysis. [2013]

4. 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]

5. England pubmed.ncbi.nlm.nih.gov

A phase I-II study of high-dose thiotepa, busulfan and cyclophosphamide as a preparative regimen for allogeneic marrow transplantation. [2013]

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

Allogeneic hematopoietic cell transplantation using fludarabine plus myeloablative busulfan and melphalan confers promising survival in high-risk hematopoietic neoplasms: a single-center retrospective analysis. [2021]

7. 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]

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

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

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

Adult recipients of matched related donor blood cell transplants given myeloablative regimens including pretransplant antithymocyte globulin have lower mortality related to graft-versus-host disease: a matched pair analysis. [2013]

10. England pubmed.ncbi.nlm.nih.gov

New myeloablative conditioning regimen with fludarabine and busulfan for allogeneic stem cell transplantation: comparison with BuCy2. [2022]