Pralatrexate + Bendamustine for T-Cell Lymphoma

Overseen By Lorenzo Iovino, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Fred Hutchinson Cancer Center

Must not be taking: Anti-lymphoma agents

Disqualifiers: Active CNS disease, Pregnancy, others

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

Compensation: Varies

Number of Visits: 7

Duration: 7 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for T-cell non-Hodgkin lymphoma that has either relapsed or is refractory. Researchers combine two drugs, pralatrexate and bendamustine (a chemotherapy drug), with whole-body radiation before a donor stem cell transplant to determine if this combination effectively kills cancer cells and prepares the body for healthy new cells. The trial seeks participants who have experienced these specific types of lymphoma relapses or treatment failures and are considering a stem cell transplant. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer treatment advancements.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that concurrent treatment with any other approved or investigational anti-lymphoma agent is not allowed at the time of starting conditioning. It's best to discuss your current medications with the trial team.

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

Research shows that pralatrexate, when used alone, often causes side effects. The most common include mouth sores, low platelet counts, fever, and vomiting, typically mild to moderate. Bendamustine has been tested for similar conditions and has shown promise, especially for patients whose cancer responds to chemotherapy.

Both drugs have been used in patients with relapsed or hard-to-treat T-cell lymphoma. While these treatments can be effective, they may cause side effects. The safety of using pralatrexate and bendamustine together remains under study. However, the separate use of both drugs with some success is encouraging.

Prospective trial participants should discuss with the study team. They can provide the most up-to-date information on safety and side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of pralatrexate and bendamustine for treating T-cell lymphoma because it could offer a new way to target cancer cells. Unlike traditional chemotherapy drugs, pralatrexate is specifically designed to interfere with the folate pathway, which is crucial for cancer cell growth. Bendamustine, on the other hand, combines the properties of both alkylating agents and purine analogs, potentially leading to a more effective attack on cancer cells. This dual approach might provide a more powerful treatment option, leading to better outcomes for patients with T-cell lymphoma compared to current standard treatments.

What evidence suggests that this trial's treatments could be effective for T-cell lymphoma?

This trial will evaluate the combination of pralatrexate and bendamustine, along with total-body irradiation (TBI) and peripheral blood stem cell transplantation (PBSC HCT), for treating T-cell lymphomas. Studies have shown that pralatrexate can help treat T-cell lymphomas, with about 31% of patients experiencing a positive response, and some even reaching complete remission. Lab studies have demonstrated bendamustine's effectiveness against T-cell lymphoma cells. These drugs may work well together because pralatrexate stops cancer cells from growing, while bendamustine damages their DNA. This combination could lead to better results for patients with hard-to-treat T-cell lymphomas. ^{1 4 6 7 8}

Who Is on the Research Team?

Lorenzo Iovino, MD, PhD

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

This trial is for patients with T-cell non-Hodgkin lymphoma that has relapsed or is refractory. Participants must be eligible for a stem cell transplant from a donor and able to undergo various diagnostic tests such as bone marrow biopsy, CT scans, and PET scans.

Inclusion Criteria

Ability to understand and sign a written informed consent document

Donor requirements for related, matched unrelated, mismatched unrelated, and haploidentical donors

Bilirubin ≤ 2.5 x institutional upper limit of normal

Exclusion Criteria

Known hypersensitivity or contraindication to any study drug

Pregnancy or lactation

I have an active brain or spinal cord condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive pralatrexate, bendamustine, and total-body irradiation followed by peripheral blood stem cell transplantation

7 days

Daily visits for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments for graft-versus-host disease and disease response

2 years

Follow-up visits at 6 months, 1 year, and 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Bendamustine
• Pralatrexate
• Total-Body Irradiation

Trial Overview The study is testing the combination of pralatrexate (a cancer growth blocker), bendamustine (DNA-damaging agent), and total-body irradiation before receiving a donor's stem cells. The goal is to determine the best dose of pralatrexate when used with bendamustine and TBI in this setting.

How Is the Trial Designed?

Group I: Treatment (pralatrexate, bendamustine, TBI, PBSC HCT) Experimental Treatment 15 Interventions

Patients receive pralatrexate IV over 3-5 minutes on day -6, bendamustine IV over 60 minutes on days -5, -4, and -3, and TBI on day -1 or 0. Patients then undergo PBSC HCT on day 0. Patients also undergo ECHO or MUGA and lumbar puncture during screening, PET-CT, MRI, bone marrow biopsy/aspiration, and blood sample collection throughout the study. In addition, patients may undergo chest X-rays as clinically indicated.

Who Is Running the Clinical Trial?

Fred Hutchinson Cancer Center

Lead Sponsor

Trials

583

Recruited

1,341,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3627334/

Safety and efficacy of pralatrexate in the treatment of patients ... The overall response rate (ORR) was 31% with CR in 17% of patients. The majority of the responses were seen in patients with a T-cell lineage lymphoma including ...

2. ashpublications.org ashpublications.org/bloodadvances/article/8/11/2601/515169/Pooled-analysis-of-pralatrexate-single-agent

Pooled analysis of pralatrexate single-agent studies in ... Patients with PTCL-NOS and AITL have a 32% estimated 5-year overall survival (OS).4. Patients with relapsed or refractory (R/R) PTCL marginally ...

3. aol.amegroups.org aol.amegroups.org/article/view/4496/5298

Bendamustine in peripheral T-cell lymphoma - Reboursiere Preclinical data have shown in vitro efficacy of bendamustine in lymphoma T-cell lines (9,10). Based on these data, bendamustine has been tested in PTCL ...

4. nature.com nature.com/articles/s41598-019-56891-0

Pralatrexate in patients with recurrent or refractory ... Our study showed relatively lower ORR and shorter PFS in patients with recurrent or refractory PTCLs treated with pralatrexate in real-world practice.

5. sciencedirect.com sciencedirect.com/science/article/pii/S0006497119813344

T-Cell Lymphoma Clinical Studies Pralatrexate in ... Conclusions: The combination of pralatrexate and CHOP was well tolerated in treatment-naive PTCL patients. MTD of pralatrexate was not reached, and the protocol ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5356759/

Bendamustine for the treatment of relapsed or refractory ... Bendamustine as single agent could be considered as a therapeutic option for relapsed or refractory PTCL, particularly in chemosensitive or AITL patients.

7. journals.sagepub.com journals.sagepub.com/doi/10.1177/2040620712445330

Safety and efficacy of pralatrexate in the treatment ... It has long been recognized that the majority of PTCLs have an inferior response to therapy and a worse prognosis compared with their B-cell counterparts.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11157204/

Pooled analysis of pralatrexate single-agent studies in ... The most common treatment-related all-grade adverse events were stomatitis, thrombocytopenia, white blood cell count decrease, pyrexia, and vomiting. Subgroup ...