Stem Cell Transplant + Chemo for Blood Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Mark Juckett

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Masonic Cancer Center, University of Minnesota

Disqualifiers: Pregnancy, Untreated infection, CNS malignancy, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial involves preparing patients with drugs and radiation before giving them a donor stem cell transplant. After the transplant, medications are used to prevent rejection of the new cells. It targets patients who need stem cell transplants.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, since this is a stem cell transplant study, it's possible that some medications might need to be adjusted or paused. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment Stem Cell Transplant + Chemo for Blood Cancer?

Research shows that using total body irradiation (TBI) with cyclophosphamide as part of the conditioning regimen for stem cell transplants can improve survival and disease control in patients with blood cancers, such as leukemia. Additionally, adding fludarabine to TBI-based regimens has been associated with better outcomes and reduced toxicity. ^{1 2 3 4 5}

Is the combination of stem cell transplant and chemotherapy generally safe for humans?

Research indicates that using fludarabine instead of cyclophosphamide in conditioning regimens for stem cell transplants can reduce toxicity and is associated with low organ toxicity and effective immunosuppression, making it generally safe for patients with conditions like Fanconi anemia and severe aplastic anemia. ^{6 7 8 9 10}

How is the Stem Cell Transplant + Chemo treatment for blood cancer different from other treatments?

This treatment combines stem cell transplantation with chemotherapy drugs like cyclophosphamide and fludarabine, and total body irradiation, which is unique because it uses a combination of therapies to prepare the body for the transplant and reduce the risk of cancer returning. The use of fludarabine instead of more toxic drugs like cyclophosphamide can reduce side effects and improve outcomes, making it a potentially safer option for patients. ^{3 6 9 11 12}

Research Team

Mark Juckett

Principal Investigator

University of Minnesota Masonic Cancer Center

Eligibility Criteria

This trial is for people aged 0-75 with various blood diseases or leukemias in remission, who have a compatible donor for stem cell transplant. They must not be pregnant, breastfeeding, or have untreated infections and should have adequate heart, lung, liver, and kidney function. HIV+ individuals can join if they're on treatment with an undetectable viral load.

Inclusion Criteria

I am between 0 and 75 years old and mostly able to care for myself.

I have a diagnosis of leukemia, lymphoma, or a related blood disorder.

My donor is a close genetic match to me.

Exclusion Criteria

I had a bone marrow transplant less than 3 months ago.

Pregnant or breast feeding

I currently have an infection that hasn't been treated.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preparative Regimen

Participants undergo a non-myeloablative cyclophosphamide/fludarabine/total body irradiation (TBI) preparative regimen

1-2 weeks

Transplantation

Participants receive a stem cell infusion followed by post-transplant cyclophosphamide (PTCy), sirolimus, and MMF for GVHD prophylaxis

Immediate post-preparative regimen

Follow-up

Participants are monitored for safety and effectiveness, including evaluation of acute and chronic GVHD, relapse rates, and overall survival

12 months

Long-term Follow-up

Participants are monitored for overall survival and transplant-related mortality

72 months

Treatment Details

Interventions

• Bone Marrow Cell Transplant (Other)
• Cyclophosphamide (Chemotherapy)
• Fludarabine (Chemotherapy)
• Peripheral Blood Stem Cell Transplant (Other)
• Sirolimus Pill (Immunosuppressant)
• Total Body Irradiation (Radiation Therapy)

Trial Overview The study tests a non-myeloablative preparative regimen using cyclophosphamide/fludarabine/total body irradiation followed by stem cell infusion from related/unrelated donors. Post-transplant care includes cyclophosphamide (PTCy), sirolimus and mycophenolate mofetil to prevent graft-versus-host disease.

Participant Groups

Group I: Cy/Flu/TBI + Post transplant CY Experimental Treatment 8 Interventions

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

Approved in Canada as Allo HSCT for:

• Acute Leukemia
• Lymphoma
• Multiple Myeloma
• Myeloproliferative Neoplasms
• Other Hematological Diseases

Approved in Japan as Allo HSCT for:

• Acute Leukemia
• Lymphoma
• Multiple Myeloma
• Myeloproliferative Neoplasms
• Other Hematological Diseases

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 meta-analysis of 15 randomized controlled trials involving 10,160 pediatric patients, total body irradiation plus cyclophosphamide (TBI/CY) was found to be more effective than busulfan plus cyclophosphamide (BU/CY) in reducing transplant failure rates and improving long-term disease-free survival rates.

The TBI/CY regimen also demonstrated a lower incidence of adverse reactions compared to the BU/CY regimen, indicating it may be a safer option for pediatric hematopoietic stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two Different Transplant Preconditioning Regimens Combined with Irradiation and Chemotherapy in the Treatment of Childhood Leukemia: Systematic Review and Meta-Analysis. Wang, X., Mu, D., Geng, A., et al.[2023]

In a study of 119 adult patients with acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplantation, the TBI/Cy conditioning regimen resulted in a median overall survival of 11 months, compared to 6.2 months for the Bu/Cy regimen.

Although both conditioning regimens showed no statistically significant differences in overall survival and disease-free survival, the Bu/Cy regimen was associated with a higher risk of relapse, indicating a potential disadvantage in using this non-TBI approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irradiation free conditioning regimen is associated with high relapse rate in Egyptian patients with acute lymphoblastic leukemia following allogeneic hematopoietic stem cell transplantation. Abdelaty, MM., Gawaly, A., Fathy, GM., et al.[2021]

In a study of 79 patients undergoing allogeneic bone marrow transplantation, the combination of etoposide, cyclophosphamide, and fractionated total-body irradiation (TBI) showed a 57% overall survival rate at 3 years for patients with early leukemia, indicating its efficacy as a preparative regimen.

Patients with advanced disease experienced significantly lower survival rates (17%) and higher toxicity, highlighting that this regimen is more effective and safer for those with early-stage hematologic malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etoposide, cyclophosphamide, total-body irradiation, and allogeneic bone marrow transplantation for hematologic malignancies. Giralt, SA., LeMaistre, CF., Vriesendorp, HM., et al.[2017]

The addition of total body irradiation (TBI) and a reduction in melphalan dosage in the FluMelTBI-75 regimen led to improved overall survival (OS) and progression-free survival (PFS) compared to the standard FluMel regimen, based on a phase II trial involving 94 patients.

FluMelTBI-75 was better tolerated, showing a significant reduction in stomatitis and improved disease control for patients not in complete remission at the time of transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced-Intensity Conditioning with Fludarabine, Melphalan, and Total Body Irradiation for Allogeneic Hematopoietic Cell Transplantation: The Effect of Increasing Melphalan Dose on Underlying Disease and Toxicity. Chen, GL., Hahn, T., Wilding, GE., et al.[2022]

In a study of 55 patients with acute myeloblastic leukemia undergoing allogeneic hematopoietic stem cell transplantation, a conditioning regimen using busulfan and fludarabine showed promising outcomes with a 1-year overall survival rate of 76% and a 3-year progression-free survival rate of 74%.

The study indicated that this regimen has acceptable levels of toxicity, with only 5.5% treatment-related mortality, and highlighted that the presence of active disease at transplantation negatively impacts survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of fludarabine- and busulfan-based conditioning regimens in patients with acute myeloblastic leukemia: 8-year experience in a single center. Kasar, M., Asma, S., Kozanoglu, I., et al.[2018]

A novel conditioning regimen for allogeneic hematopoietic stem cell transplantation (SCT) in Fanconi anemia patients showed rapid engraftment and stable donor hemopoiesis with minimal short-term toxic complications, indicating its safety and efficacy.

The conditioning regimen, which avoided irradiation and cyclophosphamide, resulted in low organ toxicity and effective immunosuppression, although some patients experienced mild acute graft-versus-host disease (GVHD).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fludarabine, low-dose busulfan and antithymocyte globulin as conditioning for Fanconi anemia patients receiving bone marrow transplantation from HLA-compatible related donors. Maschan, AA., Trakhtman, PE., Balashov, DN., et al.[2013]

In a study of 42 patients undergoing allogeneic hematopoietic stem cell transplantation, the combination of busulfan and fludarabine (BuFlu) resulted in significantly lower rates of mucositis compared to the traditional busulfan and cyclophosphamide (BuCy) regimen.

Both BuFlu and BuCy showed similar efficacy in terms of engraftment time, relapse risk, event-free survival, and overall survival, suggesting that BuFlu is a viable alternative to BuCy for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fludarabine-based myeloablative regimen as pretransplant conditioning therapy in adult acute leukemia/myelodysplastic syndrome: comparison with oral or intravenous busulfan with cyclophosphamide. Lee, JH., Choi, J., Kwon, KA., et al.[2021]

In a study involving three children with refractory severe aplastic anemia (SAA), a radiotherapy-free conditioning regimen using fludarabine and other agents was effective in preparing them for hemopoietic cell transplantation (HCT) without the development of graft-versus-host disease (GVHD).

All patients achieved normal blood counts and complete donor chimerism after the transplant, demonstrating that fludarabine-based conditioning can be a safe and effective option for children undergoing HCT from alternative donors, even after previous transplant failures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-radiotherapy conditioning with stem cell transplantation from alternative donors in children with refractory severe aplastic anemia. Urban, C., Benesch, M., Sykora, KW., et al.[2013]

In a study of 210 adult patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic cell transplantation, both busulfan/cyclophosphamide (Bu/Cy) and busulfan/fludarabine (Bu/Flu) showed similar quality of life outcomes and post-transplant complications.

Patients receiving Bu/Flu experienced faster recovery of neutrophils and platelets, along with a shorter hospital stay, although they had more cytomegalovirus (CMV) infections; overall, Bu/Flu was confirmed to be as effective as Bu/Cy in clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of busulfan/cyclophosphamide versus busulfan/fludarabine myeloablative conditioning for allogeneic hematopoietic cell transplantation in acute myeloid leukemia and myelodysplastic syndrome. Patel, SS., Rybicki, L., Pohlman, B., et al.[2021]

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]

A new phase II study with a reduced-toxicity conditioning regimen for hematopoietic stem cell transplantation (HSCT) in severe aplastic anemia (SAA) patients showed significantly improved overall survival (96.7%) and event-free survival (93.3%) compared to a previous regimen (67.9% OS and 64.3% EFS).

The new regimen, which included lower doses of cyclophosphamide (Cy) and a modified schedule for fludarabine (FLU) and antithymocyte globulin (ATG), achieved successful hematologic recovery in all patients, indicating it may be a safer and more effective option for HSCT with unrelated donors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved Outcome of a Reduced Toxicity-Fludarabine, Cyclophosphamide, plus Antithymocyte Globulin Conditioning Regimen for Unrelated Donor Transplantation in Severe Aplastic Anemia: Comparison of 2 Multicenter Prospective Studies. Kang, HJ., Hong, KT., Lee, JW., et al.[2018]

References

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

Allogeneic transplantation after a conditioning regimen with ifosfamide, carboplatin and etoposide (ICE). [2013]

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

Two Different Transplant Preconditioning Regimens Combined with Irradiation and Chemotherapy in the Treatment of Childhood Leukemia: Systematic Review and Meta-Analysis. [2023]

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

Irradiation free conditioning regimen is associated with high relapse rate in Egyptian patients with acute lymphoblastic leukemia following allogeneic hematopoietic stem cell transplantation. [2021]

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

Etoposide, cyclophosphamide, total-body irradiation, and allogeneic bone marrow transplantation for hematologic malignancies. [2017]

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

Reduced-Intensity Conditioning with Fludarabine, Melphalan, and Total Body Irradiation for Allogeneic Hematopoietic Cell Transplantation: The Effect of Increasing Melphalan Dose on Underlying Disease and Toxicity. [2022]

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

Effectiveness of fludarabine- and busulfan-based conditioning regimens in patients with acute myeloblastic leukemia: 8-year experience in a single center. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Fludarabine, low-dose busulfan and antithymocyte globulin as conditioning for Fanconi anemia patients receiving bone marrow transplantation from HLA-compatible related donors. [2013]

8. Korea (South) pubmed.ncbi.nlm.nih.gov

Fludarabine-based myeloablative regimen as pretransplant conditioning therapy in adult acute leukemia/myelodysplastic syndrome: comparison with oral or intravenous busulfan with cyclophosphamide. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Non-radiotherapy conditioning with stem cell transplantation from alternative donors in children with refractory severe aplastic anemia. [2013]

10. Saudi Arabia pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of busulfan/cyclophosphamide versus busulfan/fludarabine myeloablative conditioning for allogeneic hematopoietic cell transplantation in acute myeloid leukemia and myelodysplastic syndrome. [2021]

11. England pubmed.ncbi.nlm.nih.gov

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

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

Improved Outcome of a Reduced Toxicity-Fludarabine, Cyclophosphamide, plus Antithymocyte Globulin Conditioning Regimen for Unrelated Donor Transplantation in Severe Aplastic Anemia: Comparison of 2 Multicenter Prospective Studies. [2018]