Clinical trial NCT00918723
Conditions: Chronic Lymphocytic Leukemia Stage I Chronic Lymphocytic Leukemia Stage I Small Lymphocytic Lymphoma Stage II Chronic Lymphocytic Leukemia Stage II Small Lymphocytic Lymphoma Stage III Chronic Lymphocytic Leukemia Stage III Small Lymphocytic Lymphoma Stage IV Chronic Lymphocytic Leukemia Stage IV Small Lymphocytic Lymphoma
Sponsor: Fred Hutchinson Cancer Center
Start date: 2009-06-01; Completion date: 2016-10-01
Enrollment: 40 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This phase I/II trial studies the side effects and best dose of vorinostat when given together with fludarabine phosphate, cyclophosphamide, and rituximab and to see how well they work in treating patients with previously untreated B-cell chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fludarabine phosphate and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, may block cancer growth in different ways by targeting certain cells. Giving vorinostat together with fludarabine phosphate, cyclophosphamide, and rituximab may be a better treatment for CLL or SLL.

Detailed description:
PRIMARY OBJECTIVES:

I. To estimate the maximum tolerated dose (MTD) of vorinostat that can be combined with fludarabine (fludarabine phosphate), cyclophosphamide and rituximab (FCR) in patients with previously untreated CLL/SLL.

II. To evaluate potential efficacy in terms of 2-year after FCR plus vorinostat induction followed by rituximab plus vorinostat maintenance therapy for previously untreated CLL/SLL patients.

SECONDARY OBJECTIVES:

I. To eliminate residual disease (documented by flow cytometry and/or polymerase chain reaction \[PCR\]) in patients who have achieved a complete response (CR) after FCR plus vorinostat.

II. To estimate the rate of conversion of partial response (PR) to CR after FCR plus vorinostat.

OUTLINE: This is a phase I, dose-escalation study of vorinostat followed by a phase II study.

INDUCTION THERAPY: Patients receive vorinostat orally (PO) once daily on days 1-5 and 8-12; cyclophosphamide intravenously (IV) over 30-60 minutes and fludarabine phosphate IV over 30-60 minutes on days 1-3; and rituximab IV on day 1, 2, 3, 4, or 5. Treatment repeats every 28 days for 4-6 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Beginning 3 months after the completion of induction therapy, patients receive vorinostat PO on days 1-14 and rituximab IV on day 1. Treatment repeats every 3 months for 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for 5 years and then annually thereafter.

Arms: arm 1: INDUCTION THERAPY: Patients receive vorinostat PO once daily on days 1-5 and 8-12; cyclophosphamide IV over 30-60 minutes and fludarabine phosphate IV over 30-60 minutes on days 1-3; and rituximab IV on day 1, 2, 3, 4, or 5. Treatment repeats every 28 days for 4-6 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Beginning 3 months after the completion of induction therapy, patients receive vorinostat PO on days 1-14 and rituximab IV on day 1. Treatment repeats every 3 months for 2 years in the absence of disease progression or unacceptable toxicity.
Interventions: intervention 1: Fludarabine Phosphate intervention 2: Cyclophosphamide intervention 3: Rituximab intervention 4: Vorinostat
Intervention descriptions: intervention 1: Given IV intervention 2: Given IV intervention 3: Given IV intervention 4: Given PO

Protocol documents: