Rituximab + Chemotherapy for Hairy Cell Leukemia

Not currently recruiting at 1 trial location

Overseen By Julie C Feurtado, R.N.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Live vaccines

Disqualifiers: Active infection, Heart disease, HIV, 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: 11

Duration: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatment options for individuals with hairy cell leukemia (HCL) that hasn't responded to standard treatments or has returned. Researchers are testing whether combining rituximab, a drug that helps the immune system target cancer cells, with either pentostatin or bendamustine (both anti-cancer drugs) proves more effective than using rituximab alone. Participants will receive either rituximab with bendamustine or rituximab with pentostatin to determine which combination works best. The trial seeks individuals diagnosed with HCL that hasn't improved with previous therapies, impacting their daily life. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop taking my current medications to join the trial?

The trial requires that you stop any chemotherapy or interferon treatments at least 4 weeks before joining, and cladribine at least 6 months before. Other medications are not specifically mentioned, so 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 the combination of bendamustine and rituximab effectively treats various B-cell cancers, including some types of leukemia and lymphoma, and is generally well-tolerated. Studies have found that this combination can lead to a 100% overall response rate, with some patients achieving complete remission. Most side effects were manageable and acceptable for patients.

For the pentostatin and rituximab combination, research indicates it is safe and effective, especially for patients with recurring or stubborn hairy cell leukemia (HCL). In one study, all 18 patients responded to the treatment, with 89% achieving complete remission. Common side effects included fever, low blood cell counts, and kidney issues, but these were generally manageable.

Both combinations help the immune system target and destroy cancer cells. While these treatments have shown promise in other conditions, researchers continue to study their specific effects on HCL, especially when used with rituximab. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for hairy cell leukemia because they combine Rituximab with chemotherapy drugs like Bendamustine and Pentostatin, which might offer new benefits over standard treatments like Cladribine and Pentostatin alone. Rituximab is an antibody that specifically targets cancer cells, potentially enhancing the effectiveness of chemotherapy. Combining Rituximab with Bendamustine or Pentostatin could improve response rates or reduce side effects compared to using chemotherapy drugs alone. These combinations may represent a more targeted approach to treatment, offering hope for better outcomes for patients with hairy cell leukemia.

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

Research has shown that using rituximab with either bendamustine or pentostatin may be promising for treating hairy cell leukemia (HCL). In this trial, participants will receive different combinations of these treatments. The combination of bendamustine and rituximab proved very effective, with all patients in studies responding and many achieving complete remission. Similarly, pentostatin and rituximab together showed success, with 89% of patients in studies achieving complete remission. Both drug combinations help the immune system fight cancer cells, offering hope for patients who haven't had success with other treatments. These findings suggest that using rituximab with either of these drugs could be a strong option against HCL. ^{1 2 5 6 7}

Who Is on the Research Team?

Robert J Kreitman, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

Adults diagnosed with hairy cell leukemia that hasn't improved or has returned after standard treatments. They must have specific blood conditions, organ function within certain limits, and agree to birth control if applicable. Excluded are those with active infections, severe heart disease, HIV/hepatitis B/C, pregnant/nursing women, non-responsive to both drug combinations previously or unable to follow the trial procedures.

Inclusion Criteria

Patients who have eligible blood counts within 4 weeks from enrollment will not be considered ineligible if subsequent blood counts prior to enrollment fluctuate and become ineligible up until the time of enrollment

I need treatment for symptoms like frequent infections, low blood counts, or enlarged spleen.

My blood or lymph node test shows I have hairy cell leukemia.

Exclusion Criteria

Inability to comply with study and/or follow-up procedures

I have an active infection that hasn't been treated.

I do not have severe heart disease.

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 rituximab with either bendamustine or pentostatin for four 28-day cycles

16 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

Long-term Follow-up

Participants are monitored for disease progression and overall survival

4 years

What Are the Treatments Tested in This Trial?

Interventions

• Bendamustine
• Pentostatin
• Rituximab

Trial Overview The trial is testing whether rituximab combined with either pentostatin or bendamustine is more effective for treating hairy cell leukemia than rituximab alone. Participants will undergo four treatment cycles of 28 days each and receive these drugs on specified days while their health is closely monitored through tests and biopsies.

How Is the Trial Designed?

Group I: Non-randomized to Bendamustine 90mg/m^2 or Pentostatin 4mg/m^2 with Rituximab Experimental Treatment 10 Interventions

After initial tolerability studies are completed. Non-randomize up to 4 total participants to Bendamustine and/or Pentostatin with Rituximab

Group II: Arm 2 - Non-randomized to 90 mg/m^2 Bendamustine-Rituximab Experimental Treatment 9 Interventions

Rituximab + Bendamustine at 90 mg/m\^2 for initial tolerability study (closed)

Group III: Arm 1 - Non-Randomized to 70 mg/m^2 Bendamustine-Rituximab Experimental Treatment 9 Interventions

Rituximab + Bendamustine at 70 mg/m\^2 for initial tolerability study (closed)

Group IV: Arm 3 - Randomized to 90 mg/m^2 Bendamustine-Rituximab Active Control 9 Interventions

Rituximab + Bendamustine (at the tolerated dose)

Group V: Arm 4 - Randomized to Pentostatin-Rituximab Active Control 9 Interventions

Rituximab + Pentostatin

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5746417/

Bendamustine plus rituximab is an effective first-line ... In this work, bendamustine plus rituximab proved to be an effective and feasible first-line treatment strategy for elderly patients with TP53 un-mutated HCLv.

2. aacrjournals.org aacrjournals.org/clincancerres/article/19/22/6313/208548/Bendamustine-and-Rituximab-in-Relapsed-and

Bendamustine and Rituximab in Relapsed and Refractory ... Results: At 70 and 90 mg/m2/dose of bendamustine, overall response rate was 100%, with three (50%) and four (67%) complete remissions (CR) in each respective ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0006497119618367

Bendamustine and Rituximab for the Treatment of Multiply ... The combination of DCF and rituximab (DCFR) is reported to achieve high complete remission (CR) rates in HCL in retrospective series, but prospective phase II ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11326663/

Clinical Outcome of Patients Receiving Rituximab in ... Our study demonstrated that patients on R-Benda had good clinical outcomes, with the vast majority living beyond 50 months. Moreover, 76.1% had ...

5. journals.lww.com journals.lww.com/md-journal/fulltext/2021/02050/long_term_follow_up_after_rituximab_plus.84.aspx

Long-term follow-up after rituximab plus bendamustine in a... For patients with indolent lymphoma, rituximab plus bendamustine (RB) has proven effective in several clinical trials. Thus, RB is expected to ...

6. ashpublications.org ashpublications.org/blood/article/118/21/3909/68914/Bendamustine-and-Rituximab-for-the-Treatment-of

Bendamustine and Rituximab for the Treatment of Multiply ... Bendamustine and rituximab (BR) have been reported as effective with acceptable toxicity in several B-cell malignancies, particularly B-cell ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01059786?id=%22NCT00412594%22OR%22NCT00923013%22OR%22NCT01059786%22OR%22NCT02157181%22OR%22NCT03805932%22&rank=3

NCT01059786 | Randomized Phase II Trial of Rituximab ... Bendamustine is approved for early treatment of chronic lymphocytic leukemia (CLL) and is effective with rituximab for relapsed/refractory CLL. Its use in HCL ...