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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to treat leukemia and other blood cancers using a bone marrow transplant. Researchers are testing whether replacing cyclophosphamide with bendamustine, a chemotherapy medication, after the transplant is safe. The study targets individuals with certain high-risk blood cancers, such as acute leukemia or lymphoma, who require a transplant but lack a fully matched donor. Participants should have a partially matched family member available to donate bone marrow. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new approach.

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

Previous studies have generally shown that bendamustine is well-tolerated. It has been used successfully to treat other blood cancers, such as chronic lymphocytic leukemia. Most people handle it well, though some may experience side effects like low blood cell counts, fever, or nausea.

Cyclophosphamide is a common cancer treatment with a well-known safety record. It can also cause low blood cell counts, along with side effects like hair loss and nausea.

This new trial tests the safety of switching from cyclophosphamide to bendamustine after a bone marrow transplant. While researchers are still studying the safety of this specific combination, bendamustine's approval for other conditions suggests it might be safe here too. However, since this is an early-phase trial, researchers are still collecting data to confirm this. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using Bendamustine and Cyclophosphamide for leukemia treatment because these drugs offer a unique approach compared to standard treatments like chemotherapy with Cytarabine or Anthracyclines. Bendamustine has a distinctive mechanism of action; it not only causes DNA damage but also inhibits the repair of DNA, which might make cancer cells more susceptible to treatment. Cyclophosphamide, when combined with Bendamustine, has the potential to enhance this effect, potentially leading to better outcomes. This combination could offer a new avenue for patients who have not responded well to existing treatments.

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

Research has shown that bendamustine effectively treats certain blood cancers, such as chronic lymphocytic leukemia and non-Hodgkin's lymphoma. It has received approval for these uses, demonstrating its ability to target cancer cells. In this trial, participants will receive a combination of bendamustine and cyclophosphamide. Studies have found that this combination can be more effective for some blood cancers than standard treatments. Cyclophosphamide, commonly used in cancer treatment, is known for stopping cancer cells from growing. Together, these drugs offer hope for better results in patients with leukemia and other blood cancers. ^{6 7 8 9 10}

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 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]

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]

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

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pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/31849108/

Outcomes of bendamustine- or cyclophosphamide-based first ...

Despite improved EFS and lower toxicity, the shift from RCHOP/RCVP to BR in clinical practice did not improve OS for older patients with indolent B-cell ...

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withpower.com

withpower.com/trial/phase-2-lymphoma-10-2016-00003

BMT with Bendamustine + Cyclophosphamide for Leukemia

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7387870/

Bendamustine for patients with indolent B cell lymphoid ...

Bendamustine is efficacious in the treatment of patients with indolent B cell lymphoid malignancies. A number of randomised controlled trials have examined the ...

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oncozine.com

oncozine.com/treatment-with-bendamustine-based-regime-is-more-effective-for-indolent-non-hodgkin-lymphoma-than-standard-r-chop/

Treatment with bendamustine-based regime is more ...

Moderate to severe neutropenia (severe declines in neutrophil counts), occurred in 69% of patients treated with R-CHOP versus 29% of patients ...

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clinicaltrials.gov

clinicaltrials.gov/study/NCT00877006

NCT00877006 | Study of Bendamustine Hydrochloride and ...

The primary objective of the study is to compare the complete response (CR) rate of bendamustine and rituximab (BR) with that of standard treatment regimens.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC2697069/

Bendamustine (Treanda) For Chronic Lymphocytic Leukemia

The approval of bendamustine was based on results from an unpublished, comparative, phase 3 trial (02CLLIII) of 301 treatment-naive patients with Binet stage B ...

7.

ashpublications.org

ashpublications.org/bloodadvances/article/8/4/878/498748/Safety-of-bendamustine-for-the-treatment-of

Safety of bendamustine for the treatment of indolent non ...

Early trials in iNHL demonstrated superior clinical outcomes for bendamustine compared with other chemotherapy, including superior ...

8.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01832597

Efficacy and Safety Study of Bendamustine With or Without ...

Results of the fludarabine and cyclophosphamide combination regimen in chronic lymphocytic leukemia. J Clin Oncol. 2001 Mar 1;19(5):1414-20. doi: 10.1200 ...

9.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/nda/2008/22249s000_CrossR.pdf

nda 22-249 - accessdata.fda.gov

A single, open-label, multicenter, randomized trial has been submitted as the major trial to support the approval of bendamustine (Treanda®) for ...

10.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC3117628/

Bendamustine: Safety and Efficacy in the Management of ...

Bendamustine plus rituximab is highly effective in patients with relapsed-refractory indolent lymphoma, inducing remissions in 90% or more and a median ...