Cladribine + Rituximab 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: Antiretrovirals, Chemotherapy

Disqualifiers: Active infection, Heart disease, HIV, Pregnancy, CNS disease, 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: Unknown

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether combining cladribine and rituximab is more effective against hairy cell leukemia (HCL) than using cladribine alone. The main goal is to determine if adding rituximab can prevent the disease from returning after initial treatment. It is open to patients with HCL who have had no more than one prior round of cladribine treatment and require further treatment due to symptoms like low blood counts or an enlarged spleen. Participants will either receive both drugs simultaneously or have rituximab added later, depending on their assigned group. The study aims to improve understanding of how these drugs work together to treat HCL. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you must stop taking your current medications. However, it mentions that no other therapy, such as chemotherapy or interferon, should be taken for 4 weeks prior to study entry, and cladribine should not be taken for 6 months prior to study entry.

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

Research has shown that the combination of cladribine and rituximab is generally well-tolerated by people with hairy cell leukemia. One study found no severe side effects unrelated to blood issues directly linked to the treatment. Only one patient with a more aggressive form of the disease experienced a relapse. Another study reported long-term success with this treatment, noting that about 20% of participants had significant side effects, which were mostly manageable. These findings suggest that cladribine and rituximab are safe for many patients, although individual experiences may differ. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for Hairy Cell Leukemia use single agents like cladribine or rituximab separately, focusing on depleting cancer cells. However, combining cladribine with rituximab is unique because it pairs a chemotherapy agent with an antibody therapy, which may enhance the overall impact on the disease. This combination targets cancer cells more aggressively by using rituximab to mark the cells for destruction by the immune system while cladribine disrupts their DNA. Researchers are excited because this dual approach could potentially lead to longer remission periods and better management of minimal residual disease, offering hope for more effective, sustained treatment outcomes.

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

This trial will evaluate the effectiveness of combining cladribine and rituximab for treating hairy cell leukemia (HCL). Studies have shown that this combination is highly effective, with 97% of patients responding well and 92% achieving complete remission, meaning no signs of cancer are detected. In this trial, some participants will receive cladribine with immediate rituximab, while others will receive cladribine with rituximab delayed by at least 6 months. Rituximab alone has also proven effective for patients who did not respond to other treatments, particularly those with a variant of HCL. These findings suggest that using both cladribine and rituximab together could be a strong treatment option for people with this type of leukemia. ^{2 3 6 7 8}

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?

This trial is for adults with Hairy Cell Leukemia (HCL) who have had no more than one prior treatment with cladribine. Participants should not be pregnant, must agree to use birth control, and cannot have untreated infections or certain other health conditions. Those with the variant form of HCL (HCLv) may also join even if they've had rituximab before.

Inclusion Criteria

I can care for myself but may not be able to do heavy physical work.

I understand the study and can agree to participate.

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

Exclusion Criteria

I have symptoms from my brain or spinal cord disease.

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

I have not improved after cladribine treatment for my blood condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Cladribine 0.15 mg/Kg/day for 5 days and Rituximab 375 mg/m2/week for 8 weeks, with randomization for immediate or delayed Rituximab

8 weeks

Follow-up

Participants are monitored for MRD-free survival and other outcomes every 3 months for 1 year, then every 6 months until 2.5 years, then yearly

2.5 years

Extension

Participants with blood-MRD relapse may receive additional Rituximab treatment at least 6 months after initial treatment

What Are the Treatments Tested in This Trial?

Interventions

• Cladribine
• Rituximab

Trial Overview The study tests whether giving rituximab at the same time as cladribine is better than waiting until after cladribine treatment when minimal residual disease (MRD) might be detected. Patients will either receive both drugs simultaneously or just cladribine first, followed by rituximab later if MRD appears.

How Is the Trial Designed?

Group I: 3/Non-randomized Group Receiving Cladribine with Immediate Rituximab Experimental Treatment 8 Interventions

Non-randomized group receiving Cladribine with immediate Rituximab (before rather than after the 1st of the 5 daily doses of cladribine on day 1).

Group II: 1/Cladribine with immediate Rituximab Experimental Treatment 8 Interventions

Cladribine with immediate Rituximab.

Group III: 2/Cladribine with Rituximab Delayed by at Least 6 months After Cladribine Active Control 8 Interventions

Cladribine with Rituximab delayed by at least 6 months after Cladribine if and when minimal residual disease is detected.

Cladribine is already approved in United States, European Union for the following indications:

Approved in United States as Leustatin for:

• Hairy cell leukemia
• Chronic lymphocytic leukemia (CLL)
• Non-Hodgkin's lymphoma
• Multiple sclerosis

Approved in European Union as Litak for:

• Hairy cell leukemia
• Chronic lymphocytic leukemia (CLL)
• Non-Hodgkin's lymphoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Bendamustine-rituximab (BR) treatment showed a 100% overall response rate in patients with multiply relapsed/refractory hairy cell leukemia, with significant complete remission rates of 50% and 67% for the 70 mg/m² and 90 mg/m² dose groups, respectively.

The treatment was well-tolerated, with no significant dose-related differences in efficacy or toxicity, and the 90 mg/m² dose was selected for future studies due to its effectiveness and manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bendamustine and rituximab in relapsed and refractory hairy cell leukemia. Burotto, M., Stetler-Stevenson, M., Arons, E., et al.[2022]

Cladribine therapy has significantly improved outcomes for patients with hairy cell leukemia, leading to long-lasting remissions in most cases, and can be re-administered effectively for relapsed patients.

Alpha interferon has shown promise as an effective treatment option for selected patients with short remission durations after cladribine, including those who did not respond to rituximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interferon-alpha is a very effective salvage therapy for patients with hairy cell leukemia relapsing after cladribine: a report of three cases. Hoffman, MA.[2021]

Combining cladribine with concurrent rituximab significantly improves the rates of minimal residual disease-free complete remission (MRD-free CR) in hairy cell leukemia patients, with 97% achieving MRD-free CR compared to only 24% with cladribine alone after 6 months.

Delayed rituximab treatment after cladribine resulted in lower rates and durability of MRD-free CR, highlighting the importance of timing in treatment for better long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Phase II Study of First-Line Cladribine With Concurrent or Delayed Rituximab in Patients With Hairy Cell Leukemia. Chihara, D., Arons, E., Stetler-Stevenson, M., et al.[2021]

Treatment with purine analogs like 2-chlorodeoxyadenosine (2-CdA) leads to high remission rates and long-term survival in patients with hairy cell leukemia, although many still have minimal residual disease after achieving complete remission.

For patients who relapse, repeat treatment with 2-CdA is effective in achieving a second complete remission, and new agents like rituximab and BL22 have shown promise in treating relapsed and refractory cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

2-CdA in the treatment of hairy cell leukemia: a review of long-term follow-up. Gidron, A., Tallman, MS.[2019]

Cladribine is an effective treatment for hairy cell leukemia (HCL), but up to 37% of patients may experience relapse, especially those who do not respond completely to the initial therapy.

Rituximab, a monoclonal antibody targeting CD20, has shown effectiveness in treating relapsed HCL, as demonstrated by a case of successful multiple re-treatments in a heavily pre-treated patient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiply relapsing hairy cell leukemia responsive to repeated courses of rituximab: a case report. Buckstein, R., Patel, H., Chesney, A., et al.[2015]

In a study of 123 patients with hairy cell leukemia (HCL) diagnosed between 1996 and 2016, cladribine as a first-line treatment resulted in a high hematological complete response rate of 92%, demonstrating its efficacy in managing this rare cancer.

The median overall survival for HCL patients was over 15 years, with 5-year and 10-year survival rates of 84% and 70.5%, indicating a favorable long-term prognosis, especially compared to other treatments like IFN-α which had a higher relapse rate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A population-based study of hairy cell leukemia over a period of 20 years. Wiber, M., Maitre, E., Poncet, JM., et al.[2021]

A patient with hairy cell leukemia, who had relapsed after multiple treatments, achieved a complete response after being treated with rituximab.

The treatment resulted in a fourfold reduction of leukemic cells and restored normal blood counts, indicating rituximab's efficacy in this case.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab: a useful drug for a repeatedly relapsed hairy cell leukemia patient. Pollio, F., Pocali, B., Palmieri, S., et al.[2015]

Cladribine (CdA) demonstrated a complete remission rate of 50% and a partial remission rate of 37% in a phase II study involving 861 patients with hairy cell leukemia, indicating its efficacy as a treatment option.

While CdA was generally well tolerated, there is a noted potential increased risk for secondary malignancies, highlighting the need for ongoing monitoring of patients after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of hairy cell leukemia with 2-chlorodeoxyadenosine via the Group C protocol mechanism of the National Cancer Institute: a report of 979 patients. Cheson, BD., Sorensen, JM., Vena, DA., et al.[2022]

In a study of 24 patients with relapsed hairy cell leukemia treated with rituximab, only 25% achieved a response, indicating that rituximab has modest efficacy as a single-agent treatment in this context.

The treatment was generally safe, with only a few instances of serious side effects, such as febrile neutropenia and disseminated intravascular coagulation, suggesting that while rituximab may not be highly effective, it is relatively safe for patients who have failed previous cladribine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 study of rituximab in the treatment of cladribine-failed patients with hairy cell leukemia. Nieva, J., Bethel, K., Saven, A.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11646483/

Long-Term Results of the Sequential Combination of ... Treatment of HCL with sequential cladribine followed by rituximab is associated with excellent efficacy and safety results both in the frontline ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.e19547

A comprehensive systematic review and meta-analysis. The highest efficacy was seen in patients receiving combination therapy of cladribine and rituximab, with an ORR of 97% and CRR of 92%.

3. sciencedirect.com sciencedirect.com/science/article/pii/S2473952923005177

Single-agent rituximab is an effective salvage therapy in ... We report our single-center experience with single-agent rituximab in patients with HCL with symptomatic disease relapse and who have failed at least 1 ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT00412594

Cladribine and Rituximab in Treating Patients With Hairy ... This phase II trial studies the side effects and how well cladribine and rituximab work in treating patients with hairy cell leukemia.

5. ashpublications.org ashpublications.org/bloodadvances/article/5/23/4807/477152/Long-term-follow-up-of-a-phase-II-study-of

Long term follow-up of a phase II study of cladribine with ... With a median follow-up of 60.2 months, 5-year failure-free survival and OS were 64.3% and 51.4%, respectively, the latter influenced by several patients with ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38749022/

Long-term results of the sequential combination of cladribine ... The 10-year EFS and OS rates were 86.7% and 91.1%, respectively. Grade 3 adverse events were observed in 28 participants (20·1%), mostly due to ...

7. ashpublications.org ashpublications.org/blood/article/118/14/3818/28709/Phase-2-study-of-cladribine-followed-by-rituximab

Phase 2 study of cladribine followed by rituximab in patients ... There were no grade 3 or 4 nonhematologic adverse events directly related to the treatment. Only 1 patient (with HCLv) has relapsed; median CR ...

8. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/hon.3280

Real‐world data on diagnostics, treatment and outcomes of ... These data confirm an excellent prognosis for HCL patients treated with cladribine-based therapy. On the contrary, HCLv with its aggressive ...