Cladribine + Rituximab for Hairy Cell Leukemia

Overseen by Farhad Ravandi-Kashani

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: HIV, Hepatitis B, CNS metastases, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial studies how well two drugs, cladribine and rituximab, work together in treating patients with hairy cell leukemia. Cladribine helps stop cancer cells from growing, while rituximab helps the immune system attack cancer cells. The combination aims to be more effective in treating this type of leukemia.

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.

What data supports the effectiveness of the drug combination Cladribine and Rituximab for treating Hairy Cell Leukemia?

Research shows that Cladribine is highly effective for treating Hairy Cell Leukemia, achieving excellent remission rates, though some patients may relapse. Rituximab has been successful in treating relapsed cases and can help clear minimal residual disease, potentially improving long-term outcomes. ^{1 2 3 4 5}

Is the combination of Cladribine and Rituximab safe for treating Hairy Cell Leukemia?

Rituximab has been used safely in patients with Hairy Cell Leukemia, with some experiencing mild to moderate side effects like febrile neutropenia (fever with low white blood cell count) and reversible blood clotting issues. Cladribine has also been used effectively with a high response rate, and while relapses can occur, it is generally well-tolerated. ^{2 4 5 6 7}

How is the drug combination of Cladribine and Rituximab unique for treating hairy cell leukemia?

The combination of Cladribine and Rituximab is unique because Cladribine is a standard first-line treatment that effectively induces remission, while Rituximab, a monoclonal antibody targeting CD20, helps clear minimal residual disease (small amounts of cancer cells that remain) and is effective in relapsed cases, potentially reducing the likelihood of relapse. ^{1 2 5 8 9}

Research Team

Farhad Ravandi-Kashani

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

I am 18 years old or older.

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.

Trial Timeline

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

Treatment Details

Interventions

• Cladribine (Anti-metabolites)
• Rituximab (Monoclonal Antibodies)

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.

Participant Groups

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.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Dr. Peter WT Pisters

M.D. Anderson Cancer Center

Chief Executive Officer since 2017

MD from University of Western Ontario

Dr. Jeffrey E. Lee

M.D. Anderson Cancer Center

Chief Medical Officer

MD from Stanford University School of Medicine

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

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]

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 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 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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Randomized Phase II Study of First-Line Cladribine With Concurrent or Delayed Rituximab in Patients With Hairy Cell Leukemia. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

Rituximab: a useful drug for a repeatedly relapsed hairy cell leukemia patient. [2015]

3. United States pubmed.ncbi.nlm.nih.gov

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

4. United States pubmed.ncbi.nlm.nih.gov

Bendamustine and rituximab in relapsed and refractory hairy cell leukemia. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Multiply relapsing hairy cell leukemia responsive to repeated courses of rituximab: a case report. [2015]

6. United States pubmed.ncbi.nlm.nih.gov

Phase 2 study of rituximab in the treatment of cladribine-failed patients with hairy cell leukemia. [2021]

7. England pubmed.ncbi.nlm.nih.gov

A population-based study of hairy cell leukemia over a period of 20 years. [2021]

8. United States 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. [2021]

9. United States 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. [2022]