Ibrutinib + Fludarabine for Chronic Lymphocytic Leukemia

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Must not be taking: Immunomodulatory, Chemotherapy, Radiotherapy, others

Disqualifiers: Transformed CLL, Autoimmune anemia, Hepatitis, 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: 6

Duration: 24 weeks

29 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take certain medications like strong CYP3A inhibitors or require anticoagulation with warfarin. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug combination Ibrutinib and Fludarabine for treating Chronic Lymphocytic Leukemia?

Research shows that Ibrutinib, when combined with other treatments like bendamustine and rituximab, has a high overall response rate and can improve progression-free survival in patients with Chronic Lymphocytic Leukemia. This suggests that Ibrutinib may enhance the effectiveness of treatments like Fludarabine without adding significant side effects. ^{1 2 3 4 5}

Is the combination of Ibrutinib and Fludarabine safe for treating chronic lymphocytic leukemia?

The combination of Ibrutinib with other treatments like Fludarabine has been studied for safety in chronic lymphocytic leukemia. Common side effects of Ibrutinib include diarrhea, infections, bleeding issues, and heart problems like atrial fibrillation (irregular heartbeat). However, the combination with chemoimmunotherapy did not show additional toxicities, suggesting it may be generally safe. ^{1 2 6 7 8}

How is the drug combination of Ibrutinib and Fludarabine unique for treating chronic lymphocytic leukemia?

The combination of Ibrutinib and Fludarabine for chronic lymphocytic leukemia is unique because Ibrutinib is an oral drug that targets specific proteins in cancer cells, potentially enhancing the effectiveness of traditional chemotherapy like Fludarabine without adding extra side effects. This approach may offer a more targeted and less toxic treatment option compared to standard chemotherapy regimens. ^{2 3 6 9 10}

What is the purpose of this trial?

This is a pilot phase 2 study investigating the safety and efficacy of ibrutinib combined with short-course fludarabine in previously untreated CLL patients. Ibrutinib will be given daily until disease progression or intolerable side effects occur. Fludarabine will be given in cycles 3 and 4. The primary efficacy endpoint is the rate of complete response after 6 cycles or 24 weeks. The primary safety endpoint is the rate of treatment discontinuation after 6 cycles or 24 weeks.

Research Team

Andy Itsara, M.D.

Principal Investigator

National Heart, Lung, and Blood Institute (NHLBI)

Eligibility Criteria

This trial is for adults with previously untreated Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL), who have certain blood cell counts and are able to perform daily activities. They must not have had previous CLL treatments, be free from significant heart disease, active infections like Hepatitis B/C or HIV, and agree to use effective contraception.

Inclusion Criteria

I have CLL/SLL and have not received any treatment yet.

I can perform daily activities with minimal assistance.

Agreement to use acceptable methods of contraception, negative pregnancy test for females of childbearing potential, and willingness to participate in all study procedures

Exclusion Criteria

Psychiatric illness/social situations limiting patient's ability to comply with study requirements, inability to understand the study or give informed consent

I do not have severe liver, kidney, or other life-threatening health issues.

Major surgery within specific timeframe, currently active, clinically significant cardiovascular disease, subjects who received or require strong CYP3A inhibitors

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ibrutinib daily and fludarabine during cycles 3 and 4

24 weeks

6 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Fludarabine
• Ibrutinib

Trial Overview The study tests the combination of Ibrutinib taken daily until disease progression or side effects become intolerable, with Fludarabine given in short courses. The main goals are to see how many patients achieve a complete response after 6 cycles and monitor those who stop treatment due to side effects within the same period.

Participant Groups

Group I: Ibrutinib and short-course fludarabine Experimental Treatment 2 Interventions

* Ibrutinib 420 mg PO daily for the duration of the study * Fludarabine 25 mg/m2/day IV on days 1-5 of cycles 3 and 4

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

Approved in European Union as Fludara for:

• Chronic lymphocytic leukemia
• Mantle-cell lymphoma
• Non-Hodgkin's lymphoma

Approved in United States as Fludara for:

• Chronic lymphocytic leukemia
• Non-Hodgkin's lymphoma
• Stem Cell Transplant Conditioning

Approved in Canada as Fludara for:

• Chronic lymphocytic leukemia
• Non-Hodgkin's lymphoma

Who Is Running the Clinical Trial?

National Heart, Lung, and Blood Institute (NHLBI)

Lead Sponsor

Trials

3,987

Recruited

47,860,000+

Findings from Research

Ibrutinib is a targeted therapy specifically designed for treating chronic lymphocytic leukemia (CLL), which is a type of cancer that affects the blood and bone marrow.

This novel treatment works by inhibiting Bruton's tyrosine kinase (BTK), a key enzyme that helps cancer cells survive and proliferate, leading to improved patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib (imbruvica): a novel targeted therapy for chronic lymphocytic leukemia. Parmar, S., Patel, K., Pinilla-Ibarz, J.[2021]

In a phase 1b study involving patients with relapsed/refractory chronic lymphocytic leukemia, the combination of ibrutinib with bendamustine and rituximab (BR) showed a high overall response rate of 93.3%, with significant improvements in complete responses over time.

The study demonstrated that ibrutinib can enhance the efficacy of chemoimmunotherapy without adding prolonged hematologic toxicity, suggesting a promising treatment strategy for patients with this type of leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Bruton tyrosine kinase inhibitor ibrutinib with chemoimmunotherapy in patients with chronic lymphocytic leukemia. Brown, JR., Barrientos, JC., Barr, PM., et al.[2021]

In the phase 3 HELIOS trial involving 578 patients with previously treated chronic lymphocytic leukemia (CLL), the combination of ibrutinib and bendamustine-rituximab (BR) significantly improved progression-free survival (PFS) compared to placebo+BR, with a median PFS not reached for ibrutinib+BR versus 14.3 months for placebo+BR.

The treatment with ibrutinib+BR also resulted in a higher rate of minimal residual disease (MRD)-negative responses (26.3% vs. 6.2% for placebo+BR), indicating a deeper response to therapy, while the safety profile remained consistent with earlier reports.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated results from the phase 3 HELIOS study of ibrutinib, bendamustine, and rituximab in relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma. Fraser, G., Cramer, P., Demirkan, F., et al.[2023]

Ibrutinib (Imbruvica) is an effective treatment for chronic lymphocytic leukemia, targeting specific pathways to inhibit cancer cell growth.

Tasimelteon (Hetlioz) is beneficial for individuals with non-24-hour sleep-wake disorder, helping to regulate sleep patterns, while anti-inhibitor coagulant complex (Feiba) is used to prevent or reduce bleeding episodes in patients with hemophilia A or B, demonstrating its efficacy in managing bleeding risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmaceutical approval update. Goldenberg, MM.[2021]

Ibrutinib has shown high effectiveness as a first-line treatment for chronic lymphocytic leukemia in real-world settings, with 12-month overall survival rates between 95% and 96% and progression-free survival rates ranging from 89% to 93% across various studies involving 112 to 2033 patients.

The treatment demonstrated a strong response rate, with 71% to 90% of patients responding positively, and a significant majority (91% at 12 months and 87% at 24 months) did not require new treatment, indicating its sustained efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Literature Review of Real-World Effectiveness Results Data for First-Line Ibrutinib in Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma. Lee, P., Kistler, KD., Douyon, L., et al.[2023]

References

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

Ibrutinib (imbruvica): a novel targeted therapy for chronic lymphocytic leukemia. [2021]

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

The Bruton tyrosine kinase inhibitor ibrutinib with chemoimmunotherapy in patients with chronic lymphocytic leukemia. [2021]

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

Ibrutinib-Rituximab or Chemoimmunotherapy for Chronic Lymphocytic Leukemia. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Updated results from the phase 3 HELIOS study of ibrutinib, bendamustine, and rituximab in relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma. [2023]

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

Pharmaceutical approval update. [2021]

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

Safety and activity of BTK inhibitor ibrutinib combined with ofatumumab in chronic lymphocytic leukemia: a phase 1b/2 study. [2021]

7. France pubmed.ncbi.nlm.nih.gov

Ibrutinib (Imbruvica). Relapsed chronic lymphocytic leukaemia and mantle cell lymphoma: uncertain impact on survival. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Ibrutinib and its use in the treatment of chronic lymphocytic leukemia. [2021]

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

An oral drug for chronic lymphocytic leukemia. [2021]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Systematic Literature Review of Real-World Effectiveness Results Data for First-Line Ibrutinib in Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma. [2023]