Stem Cell Transplant + Chemo for Blood Cancer

Overseen By Mark Juckett

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Masonic Cancer Center, University of Minnesota

Disqualifiers: Pregnancy, Untreated infection, CNS malignancy, 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

56 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of stem cell transplants and chemotherapy to treat various blood cancers, such as acute leukemia and multiple myeloma. Researchers aim to determine how effectively this treatment prevents cancer recurrence. They are exploring different types of donor stem cells to identify the most effective option. The trial is open to individuals whose blood cancers are in remission and who can identify a matched donor. Those who have battled blood cancer and achieved remission may find this trial suitable. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Studies have shown that treatment using cyclophosphamide, fludarabine, and total body irradiation (TBI) is generally well-tolerated. One study found that a version of this treatment with fewer side effects was safe for children with blood cancers, regardless of the donor. This indicates the treatment didn't cause many severe long-term side effects.

However, another study noted that high doses of cyclophosphamide could lead to more complications in the first six months after treatment. Therefore, doctors must carefully control the drug dosage.

Overall, the treatment shows promise for its safety, but it carries some risks that require monitoring. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of stem cell transplants and chemotherapy for blood cancer because it offers a multi-faceted approach that could enhance treatment effectiveness. Unlike standard chemotherapy alone, this approach uses bone marrow and peripheral blood stem cell transplants to rebuild healthy blood cells after intensive chemo and total body irradiation. Cyclophosphamide and fludarabine are used to prepare the body for the transplant, helping to better target and destroy cancer cells. This combination could result in more thorough cancer eradication and improved recovery of healthy blood cells, potentially leading to better patient outcomes compared to traditional treatments.

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

Research has shown that combining the drugs cyclophosphamide and fludarabine with total body irradiation (TBI) can help treat blood cancers. In this trial, participants will receive this combination as part of the treatment regimen before a stem cell transplant. One study found that this combination prepares patients for a stem cell transplant, even if the donor isn't a perfect match. It also proved effective in children with these cancers. These findings suggest that this treatment can help the body accept new stem cells, which is crucial for fighting blood cancers. ^{1 5 6 7 8}

Who Is on the Research Team?

Mark Juckett

Principal Investigator

University of Minnesota Masonic Cancer Center

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Bone Marrow Cell Transplant
• Cyclophosphamide
• Fludarabine
• Peripheral Blood Stem Cell Transplant
• Sirolimus Pill
• Total Body Irradiation

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.

How Is the Trial Designed?

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

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

Approved in United States as Allo HSCT for:

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

Approved in European Union as Allo HSCT for:

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

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+

Published Research Related to This Trial

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 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]

An ifosfamide-based conditioning regimen (ICE) for allogeneic stem cell transplantation was successful, using ifosfamide, carboplatin, and etoposide over 6 days, demonstrating effective immunosuppression without the need for cyclophosphamide or total body irradiation (TBI).

The regimen led to prompt engraftment of donor cells, with neutrophil counts exceeding 20 x 10^9/L by day 10 and platelet counts exceeding 20 x 10^9/L by day 18, confirming the efficacy of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic transplantation after a conditioning regimen with ifosfamide, carboplatin and etoposide (ICE). Oblon, DJ., Paul, S., Yankee, R.[2013]

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]

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 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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT00255684

Study Details | NCT00255684 | Fludarabine, ... PURPOSE: This clinical trial is studying how well giving fludarabine and cyclophosphamide together with total-body irradiation followed by ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8627667/

Higher Fludarabine and Cyclophosphamide Exposures ... Higher Fludarabine and Cyclophosphamide Exposures Lead to Worse Outcomes in Reduced-Intensity Conditioning Hematopoietic Cell Transplantation for Adult ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00134004

Fludarabine, Cyclophosphamide, and Total-Body ... PURPOSE: This phase II trial is studying how well giving fludarabine and cyclophosphamide together with total-body irradiation works in treating ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11646108/

Long‐Term Outcomes of Reduced‐Toxicity Conditioning ... 8‐Gy TBI/FLU/CY RTC was safe in children with hematological malignancies, regardless of the donor source.

5. sciencedirect.com sciencedirect.com/science/article/pii/S2666636724005852

Total Body Irradiation and Fludarabine with Post- ... In this retrospective study, we investigated outcomes of patients who underwent mismatched donor (related or unrelated) HCT with a radiation-based myeloablative ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39673729/

Long-Term Outcomes of Reduced-Toxicity Conditioning ... Long-Term Outcomes of Reduced-Toxicity Conditioning Using 8-Gray Total Body Irradiation, Fludarabine, and Cyclophosphamide in Children, Adolescents, and Young ...

7. astctjournal.org astctjournal.org/article/S2666-6367(21)00932-5/fulltext

Higher Fludarabine and Cyclophosphamide Exposures ... High cyclophosphamide (Cy) exposure was associated with worse day 100 and day 180 nonrelapse mortality (NRM) and worse day 180 overall survival (OS).

8. researchgate.net researchgate.net/publication/387061944_Long-Term_Outcomes_of_Reduced-Toxicity_Conditioning_Using_8-Gray_Total_Body_Irradiation_Fludarabine_and_Cyclophosphamide_in_Children_Adolescents_and_Young_Adults_With_Hematological_Malignancies

Long‐Term Outcomes of Reduced‐Toxicity Conditioning ... Recent studies have indicated that total body irradiation (TBI)‐based reduced‐toxicity conditioning (RTC) may be a potential treatment modality, ...