What side effects are associated with this type of intervention?

Common treatments for blood cancers, such as cyclophosphamide, often lead to a range of side effects. These include cytopenias (reduced blood cell counts), which can result in anemia, increased risk of infections, and bleeding complications. Gastrointestinal issues like nausea, vomiting, and diarrhea are also frequent. Long-term use can lead to secondary malignancies, cardiopulmonary complications, and potential teratogenic effects. Additionally, mucocutaneous ulcers and peripheral neuropathy are notable side effects. These treatments require careful monitoring and supportive care to manage these adverse effects effectively.

What prior FDA approvals exist?

Cyclophosphamide, an immunosuppressive and chemotherapeutic agent, has been widely used in the treatment of various blood cancers. It is often part of combination regimens such as Hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) for acute lymphoblastic leukemia (ALL) and in protocols for multiple myeloma involving combinations like bortezomib, dexamethasone, and cyclophosphamide. Additionally, cyclophosphamide is used in conditioning regimens for bone marrow transplantation to reduce the risk of graft-versus-host disease (GVHD). These regimens have been studied extensively and have shown efficacy in improving patient outcomes in blood cancers.

What other types of research exist?

Promising alternatives to cyclophosphamide for blood cancer patients include: 1) Ibrutinib-based therapy, which has shown superior efficacy in CLL patients with del17p, TP53 mutation, or IGHV-unmutated CLL. 2) Venetoclax plus obinutuzumab, which is effective for older or frail adults with IGHV-mutated CLL. 3) Non-immunosuppressive analogues of Cyclosporin A, such as SDZ PSC 833, which have demonstrated cytotoxic activity in tumor cells from patients with hematological malignancies. 4) Pembrolizumab, particularly for patients with head and neck cancer, which may also be relevant for certain blood cancers. These alternatives offer potential benefits in terms of efficacy and reduced side effects.

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Alkylating agents

Reduced-Dose Cyclophosphamide for Blood Cancer

Phase 1 & 2

Recruiting

Led By Christopher G Kanakry, M.D.

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Subjects must have a histologically or cytologically confirmed hematologic malignancy with standard indication for allogeneic hematopoietic cell transplantation

Age criteria: 60-85 years, or age 18-60 years and unfit for myeloablative conditioning

Must not have

Poorly controlled malignant indication for transplantation

Uncontrolled intercurrent illness that would make it unsafe to proceed with transplantation

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 1 year

Awards & highlights

Summary

This trial is testing if a lower dose of cyclophosphamide after a bone marrow transplant can help adults with difficult-to-treat blood cancers. The aim is to prevent complications from donor cells attacking the body while reducing side effects. The study focuses on patients who are older, less fit, or have not had success with other treatments.

Who is the study for?

Adults aged 18-85 with blood cancers not responding well to standard treatments or at high relapse risk, and their donors. Participants must have a suitable donor, agree to contraception use, and meet specific health criteria like adequate organ function. Excluded are those on other investigational drugs, with poorly controlled cancer or significant unrelated illnesses.

What is being tested?

The trial is testing if a lower dose of cyclophosphamide can reduce side effects while still preventing graft-versus-host disease in bone marrow transplant patients. It includes chemotherapy, radiation, and post-transplant medications over several weeks with follow-up visits up to five years.

What are the potential side effects?

Potential side effects include reactions from the chemotherapy drug cyclophosphamide such as nausea, hair loss, mouth sores; Mesna may cause allergic reactions; Filgrastim can lead to bone pain; TBI might result in fatigue; Mycophenolate Mofetil could cause stomach issues; Sirolimus may increase infection risk.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have a blood cancer confirmed by lab tests, needing a stem cell transplant.

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I am between 60-85 years old, or 18-60 and not suitable for intensive treatment.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My cancer is not well-managed and I need a transplant.

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I do not have any severe illnesses that would make a transplant unsafe for me.

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I have an active cancer that is not related to blood.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 1 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~1 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and 1 year for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

determine if optimal dose of PTCy to prevent grade III-IV acute GVHD (aGVHD) at day +60

Secondary study objectives

Chronic GVHD at one year

Estimation of platelet engraftment, neutrophil engraftment.

Grade II-IV acute GVHD at day 100 and 200

+5 more

Trial Design

5Treatment groups

Experimental Treatment

Active Control

Group I: Younger, HLA-mismatchedExperimental Treatment8 Interventions

Subjects age 18-60 unfit for MAC with hematologic malignancies and an HLA-haploidentical or HLA-mismatched unrelated donor

Group II: Younger, HLA-matchedExperimental Treatment8 Interventions

Subjects age 18-60 unfit for MAC with hematologic malignancies and an HLA-matched related or unrelated donor

Group III: Older, HLA-mismatchedExperimental Treatment8 Interventions

Subjects age 60-85 with hematologic malignancies and an HLA-haploidentical or HLA-mismatched unrelated donor

Group IV: Older, HLA-matchedExperimental Treatment8 Interventions

Subjects age 60-85 with hematologic malignancies and an HLA-matched related or unrelated donor

Group V: DonorsActive Control1 Intervention

Collection of research samples on bone marrow donors

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Filgrastim

2000

Completed Phase 3

~3690

Cyclophosphamide

2010

Completed Phase 4

~2320

Mesna

2003

Completed Phase 2

~1380

Total Body Irradiation (TBI)

2016

Completed Phase 3

~1220

Mycophenolate Mofetil

1997

Completed Phase 4

~2380

Allogeneic HSCT

2015

Completed Phase 2

~60

Fludarabine

2012

Completed Phase 4

~1860

Sirolimus

2013

Completed Phase 4

~2750

0 / 5Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Cyclophosphamide, a common treatment for blood cancers, acts by cross-linking DNA strands, thereby preventing cell division and inducing cell death in rapidly dividing cells like cancer cells. Its immunosuppressive properties also help prevent graft-versus-host disease (GVHD) in bone marrow transplant patients. This dual action is crucial for blood cancer patients as it reduces malignant cells and supports successful transplantation.

Optimizing the Outcome of Anti-Myeloma Treatment with Daratumumab.