Dasatinib With Fludarabine and Rituximab in Relapsed and Refractory CLL and SLL

NCT01173679 | Terminated Phase 2 Results DMC

• 1 other identifier: 09-325
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 3

Brief Summary

Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL) are similar diseases of the white blood cells and are typically treated the same way. Recent research shows that a key enzyme in CLL cells is responsible for cell survival. This enzyme is called LYN kinase. Laboratory studies show that inhibition of LYN kinase in CLL cells results in the death of CLL cells. Dasatinib has the ability to inhibit LYN kinase and, therefore, should have some effect on CLL cells. The purpose of this study is to see of the study drug dasatinib, in combination with fludarabine and rituximab, is safe and effective to use for people with relapsed or refractory CLL/SLL.

Conditions

Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Keywords

CLL; fludarabine; rituximab; dasatinib; refractory; relapsed

Outcome Measures

Primary Outcomes (1)

• Response Rate

  To describe the response rate of complete response (CR) and partial response (PR) to treatment with this drug combination (SD=stable disease, PD=progressive disease)

  2 years

Secondary Outcomes (2)

• Progression-Free and Overall Survival

  2 years

• Toxicities

  2 years

Study Arms (1)

dasatinib, rituximab, fludarabine

OTHER

Single-arm, open-label

Drug: dasatinib; Drug: Rituximab; Drug: fludarabine

Interventions

dasatinib DRUG

Taken orally once a day on days 1-14 of each 28-day cycle

dasatinib, rituximab, fludarabine

Rituximab DRUG

Given intravenously, 375 mg/m2 each cycle (dose split, given on Days 3+4 of cycle 1, variable after that).

dasatinib, rituximab, fludarabine

fludarabine DRUG

Given intravenously, 25 mg/m2/day, for 3 doses per cycle (Days 3-5 in cycle 1, Days 1-3 after that)

dasatinib, rituximab, fludarabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• CLL/SLL with cells positive by flow cytometry (or immunostaining) for CD19, CD23, and CD5. Patients may be CD23 negative as long as they are also cyclin D1 negative or t(11;14) negative.
• Participants must have received at least 1 prior regimen containing a purine analogue or have received at least 2 chemotherapy regimens not containing a purine analogue. Patients may be refractory to single-agent purine analogue treatment, but patients may not be refractory to a combination of purine analogue with rituximab. Patients may have received rituximab.
• years of age or older
• Able to take oral medications
• ECOG Performance Status of 2 or better
• Adequate organ function to tolerate chemotherapy
• Women of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to the start of study drug administration and agree to use and utilize an adequate method of contraception throughout treatment and for at least 4 weeks after study is stopped.
• Require treatment based on 1996 NCI-WG criteria updated in 2008 by the IWCLL
• Patient agrees to discontinue St. John's Wort while receiving dasatinib therapy and stop at least 5 days before starting dasatinib.
• Patient agrees that IV bisphosphonates will be withheld for the first 8 weeks of dasatinib

You may not qualify if:

• Pregnant or breastfeeding women
• Uncontrolled angina, congestive heart failure, or MI within 6 months
• Diagnosed or suspected congenital long QT syndrome
• Any history of clinically significant ventricular arrhythmias
• Prolonged QTc interval on pre-entry ECG
• Uncontrolled hypertension
• Hypokalemia or hypomagnesemia that is not corrected prior to dasatinib administration
• Patients should not be taking drugs that are generally accepted to have a risk of causing Torsades de Pointes
• Known HIV positive
• Known significant bleeding disorder unrelated to CLL
• Any significant pleural or pericardial effusion
• Patients may not have another malignancy that is uncontrolled or requires treatment within a year of starting this study.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Dana-Farber Cancer Institute: collaborator
• Beth Israel Deaconess Medical Center: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Recurrence

Interventions

Dasatinib; Rituximab; fludarabine

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Philip C. Amrein, M.D.
• Organization: Massachusetts General Hospital

pamrein@partners.org

6177243456

Study Officials

• Philip Amrein, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: July 28, 2010
• First Posted: August 2, 2010
• Study Start: July 1, 2010
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: April 14, 2017
• Results First Posted: March 20, 2017

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)