BMT with Bendamustine + Cyclophosphamide for Leukemia

Overseen By Michele Chu-Pilli

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Arizona

Disqualifiers: Refractory leukemia, CNS leukemia, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The purpose of this study is to evaluate the safety of progressively substituting day +3 and +4 post-transplant cyclophosphamide (PT-CY) with post-transplant bendamustine (PT-BEN) in myeloablative (MAC) haploidentical hematopoietic cell transplantation (HHCT) for patients with hematological malignancies. The goal of the Phase 1 component of the study is to evaluate the safety of progressively substituting post-transplant cyclophosphamide (PT-CY) given on Days +3 and +4 with bendamustine (PT-BEN). The Phase I component of the study has been completed. The Phase Ib component of the study will continue to evaluate the safety and efficacy of subjects who receive PT-BEN on Days +3 and +4 at the maximum tolerated dose determined by Phase I. The Phase Ib component of the study has been completed. Approximately, 18-36 subjects will be treated as part of Phase I and 15 as part of Phase Ib. Approximately 18 subjects will be used as controls, subjects that receive no PET-BEN, for direct comparison. Total, approximately 38-56 treatment and control patients and 38-56 donor subjects will be enrolled.

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 a clear answer based on your specific situation.

Is the combination of Bendamustine and Cyclophosphamide safe for humans?

Bendamustine has been shown to be generally safe in humans, with common side effects including nausea, fatigue, vomiting, fever, diarrhea, constipation, and headache. Serious side effects are less common but can include neutropenic fever (a type of fever that occurs when white blood cell counts are low), bone pain, and renal insufficiency (kidney problems). ^{1 2 3 4 5}

How is the drug combination of Bendamustine and Cyclophosphamide unique for treating leukemia?

The combination of Bendamustine and Cyclophosphamide for leukemia is unique because it explores the use of Bendamustine, which is typically used in lymphoma treatments, as a substitute for other drugs in conditioning regimens before bone marrow transplantation. This approach may offer different toxicity profiles and potentially improve outcomes like earlier engraftment and reduced viral reactivation compared to traditional regimens. ^{6 7 8 9 10}

What data supports the effectiveness of the drug Bendamustine combined with Cyclophosphamide for treating leukemia?

Bendamustine has shown effectiveness in treating various blood cancers, including chronic lymphocytic leukemia and non-Hodgkin's lymphoma, and has been approved by the FDA for these uses. Additionally, studies suggest that Bendamustine can work well with other cancer drugs, like Cyclophosphamide, to enhance treatment effects, especially in resistant cases. ^{1 2 3 6 11}

Who Is on the Research Team?

Emmanuel Katsanis, MD

Principal Investigator

The University of Arizona Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with high-risk blood cancers like ALL, AML, CML, MDS, and various lymphomas who need a bone marrow transplant but don't have a fully matched donor. They must have at least one half-matched (haploidentical) related donor available and be able to consent to the study. People can't join if they have untreated brain leukemia, severe heart or liver problems, active infections or certain other health issues.

Inclusion Criteria

I need a stem cell transplant for my high-risk cancer but don't have a matching donor.

My cancer is in remission and is one of the specified high-risk types.

I have a family member who can donate bone marrow to me.

Exclusion Criteria

Investigator's discretion that patient's participation would not be in their best interest or unable to adhere to study requirements

My lung function is significantly reduced.

My acute leukemia is not responding to treatment or is getting worse.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase I

Evaluate the safety of substituting post-transplant cyclophosphamide with bendamustine on Days +3 and +4 after BMT

6 dose levels

Multiple visits for dose escalation and monitoring

Treatment Phase Ib

Evaluate safety and efficacy of PT-BEN at maximum tolerated dose on Days +3 and +4

Duration not specified

Multiple visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including immune reconstitution and infection risk

3 years

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Bendamustine
• Cyclophosphamide

Trial Overview The trial tests replacing some doses of post-transplant cyclophosphamide (a standard drug given after bone marrow transplants) with bendamustine to see if it's safe and works well in haploidentical bone marrow transplantation for blood cancer patients.

How Is the Trial Designed?

Group I: Cyclophosphamide and Bendamustine Experimental Treatment 2 Interventions

Experimental: Cyclophosphamide and Bendamustine Control: Cyclophosphamide Interventions: * Drug: Bendamustine * Drug: Cyclophosphamide

Bendamustine is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Treanda for:

• Chronic lymphocytic leukemia
• Non-Hodgkin lymphoma

Approved in European Union as Ribomustin for:

• Chronic lymphocytic leukemia
• Non-Hodgkin lymphoma
• Multiple myeloma

Approved in Canada as Levact for:

• Chronic lymphocytic leukemia
• Non-Hodgkin lymphoma

Approved in Japan as Bendamustine hydrochloride for:

• Chronic lymphocytic leukemia
• Non-Hodgkin lymphoma

Who Is Running the Clinical Trial?

University of Arizona

Lead Sponsor

Trials

545

Recruited

161,000+

Published Research Related to This Trial

Bendamustine hydrochloride is a newer alkylating agent that has shown promise in treating resistant or refractory cancers due to its unique pharmacological properties.

The article reviews clinical trials demonstrating bendamustine's effectiveness both as a standalone treatment and in combination therapies for various solid tumors and blood cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bendamustine hydrochloride - a renaissance of alkylating strategies in anticancer medicine. Eichbaum, M., Bischofs, E., Nehls, K., et al.[2017]

Bendamustine shows promising synergistic effects when combined with other anti-cancer drugs, such as alkylating agents and pyrimidine analogues, for treating resistant lymphoid malignancies, as demonstrated in various cancer cell lines.

The drug enhances the uptake of cytosine arabinoside (Ara-C) and increases the expression of transporters that facilitate this process, suggesting that its unique properties may improve the effectiveness of combination therapies in difficult-to-treat cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Purine analog-like properties of bendamustine underlie rapid activation of DNA damage response and synergistic effects with pyrimidine analogues in lymphoid malignancies. Hiraoka, N., Kikuchi, J., Yamauchi, T., et al.[2022]

Bendamustine is a unique cancer treatment that combines alkylating and antimetabolite properties, making it effective against certain blood cancers like chronic lymphocytic leukemia and non-Hodgkin's lymphoma.

It has been approved by the US FDA for patients whose cancer has not responded to or has progressed after rituximab treatment, and it can be used alone or in combination with other therapies, showing promising efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bendamustine in chronic lymphocytic leukemia and non-Hodgkin's lymphoma. Ujjani, C., Cheson, BD.[2015]

In a study of 34 patients with multiple myeloma, the combination of bendamustine, etoposide, and dexamethasone (BED) successfully mobilized hematopoietic stem cells in all participants, with a median yield of 21.60 million cells per kg of body weight.

The treatment was effective and safe, with 88% of patients needing only one apheresis session, although six patients experienced serious nonhematologic adverse events, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bendamustine, etoposide and dexamethasone to mobilize peripheral blood hematopoietic stem cells for autologous transplantation in patients with multiple myeloma. Green, DJ., Bensinger, WI., Holmberg, LA., et al.[2023]

Citations

1. Spain pubmed.ncbi.nlm.nih.gov

Bendamustine hydrochloride - a renaissance of alkylating strategies in anticancer medicine. [2017]

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

Purine analog-like properties of bendamustine underlie rapid activation of DNA damage response and synergistic effects with pyrimidine analogues in lymphoid malignancies. [2022]

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

Bendamustine in chronic lymphocytic leukemia and non-Hodgkin's lymphoma. [2015]

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

Progressive substitution of posttransplant cyclophosphamide with bendamustine: A phase I study in haploidentical bone marrow transplantation. [2022]

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

Bendamustine, etoposide and dexamethasone to mobilize peripheral blood hematopoietic stem cells for autologous transplantation in patients with multiple myeloma. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

Bendamustine: something old, something new. [2020]

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

Bendamustine: a novel cytotoxic agent for hematologic malignancies. [2015]

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

A retrospective, matched paired analysis comparing bendamustine containing BeEAM versus BEAM conditioning regimen: results from a single center experience. [2019]

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

Z-BeEAM (Ibritumomab tiuxetan, Bendamustine, Etoposide, Cytarabine, Melphalan) before autologous stem cell transplantation is safe and efficient for refractory large B-cell lymphoma. [2020]

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

Bendamustine-induced nephrogenic diabetes insipidus - A case report. [2021]

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

BendaEAM versus BEAM as conditioning regimen for ASCT in patients with relapsed lymphoma (BEB): a multicentre, randomised, phase 2 trial. [2023]