A Phase II Study Using Ibrutinib and Short-Course Fludarabine in Treatment-Naive CLL

Phase 2

Active, not recruiting

Conditions: Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma

Interventions: Drug: Ibrutinib
Drug: Fludarabine

Registration Number: NCT02514083

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

Brief Summary: 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.

Detailed Description: Chronic lymphocytic leukemia (CLL) and/or small lymphocytic lymphoma (SLL) are tumors of B cells that often affect elderly patients. While the cause of CLL is still unclear, studies have indicated critical factors required for the tumor cells. First, CLL cells grow and survive because they receive signals through the B-cell receptor (BCR); and second, CLL cells benefit from interactions with other cells, especially T cells.

The stimulation through the BCR can be reduced with ibrutinib, which is an oral drug that selectively inhibits Bruton's tyrosine kinase (BTK). In clinical trials, ibrutinib demonstrated safety and high response rates in patients with high-risk disease. Ibrutinib has gained FDA approval as a treatment for CLL patients with 17p deletion and for those who had at least one prior therapy. However, single-agent ibrutinib has limitations; the drug does not eliminate all the tumor cells, and, with time, the tumor cells may become resistant. Therefore, a combination of ibrutinib with other drugs could be beneficial. Here we chose fludarabine because it is a well-tolerated drug that has been used widely to treat CLL. Also, fludarabine can kill both malignant B cells and T cells that support the growth of leukemia cells. With this approach, we hope to restore a healthier immune system.

This study will investigate the safety and efficacy of ibrutinib combined with fludarabine. This protocol is intended for previously untreated CLL patients. Ibrutinib will be given daily until disease progression or intolerable side effects occur. Fludarabine will be given only in cycles 3 and 4.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 29

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Ibrutinib and short-course fludarabine	Ibrutinib	* 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
Ibrutinib and short-course fludarabine	Fludarabine	* 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

Primary Outcome Measures

Name	Time	Method
Rate of Complete Response at 24 Weeks	24 weeks	Rate of complete response at 24 weeks or after 6 cycles. Response assessment was conducted according to the guidelines from the 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL).
Rate of Treatment Discontinuation Within the First 24 Weeks	24 weeks	Rate of treatment discontinuation within the first 24 weeks or 6 cycles due to intolerable side effects from study therapy

Secondary Outcome Measures