Cladribine + Rituximab for Hairy Cell Leukemia

Overseen By Farhad Ravandi-Kashani

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: HIV, Hepatitis B, CNS metastases, 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: 3

Duration: 12 weeks

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of two drugs, cladribine and rituximab, in treating hairy cell leukemia, a rare blood cancer. Cladribine aims to stop cancer cell growth, while rituximab helps the immune system target and attack these cells. The trial seeks patients with hairy cell leukemia who have had no more than one previous treatment. Participants will receive both drugs to determine if this combination can effectively kill more cancer cells. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in cancer therapy.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have taken any investigational agents or chemotherapy in the last 4 weeks before starting the trial.

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

Research has shown that using cladribine followed by rituximab to treat hairy cell leukemia is safe. Studies report that patients tolerate this combination well, with no major safety concerns.

Cladribine is a chemotherapy drug that stops cancer cells from growing or spreading. Rituximab is a type of immunotherapy that helps the immune system attack cancer cells. Together, these drugs have proven effective and safe for patients, both for initial treatment and when the cancer returns.

Overall, this combination works effectively without causing serious side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of cladribine and rituximab for treating hairy cell leukemia because it offers a potentially more effective approach than current treatments. Cladribine works by disrupting DNA synthesis in cancer cells, leading to their death, while rituximab targets and eliminates specific B-cells, including those involved in hairy cell leukemia. This combination aims to enhance the destruction of cancerous cells more efficiently and might provide a quicker response than existing therapies, which typically involve chemotherapy alone.

What evidence suggests that cladribine and rituximab might be an effective treatment for hairy cell leukemia?

Research has shown that using cladribine and rituximab together, as studied in this trial, effectively treats hairy cell leukemia. One study found that this combination helped 97% of patients improve, with 92% showing no signs of cancer after treatment. This indicates significant improvement for most patients, with many achieving complete remission. The treatment combines chemotherapy and immunotherapy to effectively target and kill cancer cells. Previous patients have experienced excellent results, making this combination a promising option for hairy cell leukemia. ^{2 3 6 7 8}

Who Is on the Research Team?

Farhad Ravandi-Kashani

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with hairy cell leukemia who may have had one prior therapy. They must not be pregnant and should agree to use birth control. Participants need a performance status of <=3, acceptable kidney and liver function tests, and no recent investigational drugs or active infections.

Inclusion Criteria

Bilirubin less than or equal to 3.0

Women of child-bearing potential must use birth control (oral contraceptive, barrier, abstinence or any other acceptable method) for the duration of the study

No prior investigational agent in the 4 weeks prior to initiation of therapy

Exclusion Criteria

I have been diagnosed with HIV, hepatitis B, or hepatitis C.

My cancer has spread to my brain or spinal cord.

My heart condition severely limits my daily activities.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cladribine intravenously over 2 hours once daily for 5 days, followed by rituximab IV once weekly for 8 weeks beginning on day 28

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Cladribine
• Rituximab

Trial Overview The study is testing the combination of Cladribine (a chemotherapy drug) with Rituximab (an immunotherapy antibody) to see if they work better together in treating hairy cell leukemia by killing cancer cells or stopping their growth.

How Is the Trial Designed?

Group I: Treatment (cladribine and rituximab) Experimental Treatment 3 Interventions

Patients receive cladribine IV over 2 hours QD on days 1-5 and rituximab IV once weekly for 8 weeks beginning on day 28 in the absence of disease progression or unacceptable toxicity.

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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]

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]

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 ... Treatment of HCL with sequential cladribine followed by rituximab is associated with excellent efficacy and safety results both in the frontline and relapsed ...

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 ... We conducted this study to determine the feasibility and safety of cladribine followed by rituximab in patients with hairy cell leukemia

8. mdanderson.elsevierpure.com mdanderson.elsevierpure.com/en/publications/long-term-results-of-the-sequential-combination-of-cladribine-and

Long-term results of the sequential combination ... Treatment of HCL with sequential cladribine followed by rituximab is associated with excellent efficacy and safety results both in the frontline and relapsed ...