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

Primary Purpose

Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

dasatinib

Rituximab

fludarabine

About this trial

This is an interventional treatment trial for Chronic Lymphocytic Leukemia focused on measuring CLL, fludarabine, rituximab, dasatinib, refractory, relapsed

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.
18 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

Exclusion Criteria:

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.

Sites / Locations

Massachusetts General Hospital
Beth Israel Deaconess Medical Center
Dana-Farber Cancer Institute

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

dasatinib, rituximab, fludarabine

Arm Description

Single-arm, open-label

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

Progression-Free and Overall Survival

To describe the progression-free and overall surivial

Toxicities

Dasatinib may enhance the myelosuppression expected from fludarabine. This toxicity will be monitored with frequent CBC's. If after Day 21 of a cycle there is a grade 4 cytopenia, a dose reduction will occur in the next cycle of treatment, and that cycle cannot start until the ANC > 1,000 and the platelets > 25,000. There is also a risk for pleural effusions with dasatinib, but the risk will be low, since there is a break from dasatinib dosing on days 15-28 of each cycle. Nevertheless, if a grade 2 pleural effusion occurs, there will be a dose reduction in the next cycle of treatment.

Full Information

NCT ID

NCT01173679

First Posted

July 28, 2010

Last Updated

March 17, 2017

Sponsor

Massachusetts General Hospital

Collaborators

Dana-Farber Cancer Institute, Beth Israel Deaconess Medical Center, Bristol-Myers Squibb

1. Study Identification

Unique Protocol Identification Number

NCT01173679

Brief Title

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

Official Title

Phase II Trial of Dasatinib With Fludarabine and Rituximab in Relapsed and Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

Study Type

Interventional

2. Study Status

Record Verification Date

March 2017

Overall Recruitment Status

Terminated

Why Stopped

Slow accrual

Study Start Date

July 2010 (undefined)

Primary Completion Date

January 2015 (Actual)

Study Completion Date

January 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Massachusetts General Hospital

Collaborators

Dana-Farber Cancer Institute, Beth Israel Deaconess Medical Center, Bristol-Myers Squibb

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

Detailed Description

Since the purpose of the study is to determine the response rate of the 3 drug regimen, everyone who participates will receive the same dose of the study drug, dasatinib and the 2 standard drugs, fludarabine and rituximab. Participants will receive the drugs dasatinib, fludarabine, and rituximab at the following time points through each cycle of treatment. A cycle of study treatment is 28 days. Dasatinib pills will be taken orally each day for the first 2 weeks of each cycle. Fludarabine will be give intravenously on three days of each cycle (Days 3-5 in the first cycle, days 1-3 after that). Rituximab will be given intravenously with a total dose of 375 mg/m2 each cycle (split on Days 3+4 in the first cycle and at the discretion of the treating physician after that on Days 1-3). The following procedures will be repeated throughout the study: medical history review; physical exam; performance status test; blood tests and EKG. They will occur daily during the first week of treatment, then weekly for the rest of cycle 1. After cycle 1 these procedures will be done once a week for 4 weeks then once a month for 6 months. Tumor assessments will be repeated once every 2 months for the first six months of the study, and then once every 6 months after that. Blood samples will be obtained in the first 5 days of treatment for pharmacokinetic studies and pharmacodynamic studies. Participants that are benefiting from the study treatment after the first cycle can continue to receive an additional 6 cycles of study treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma

Keywords

CLL, fludarabine, rituximab, dasatinib, refractory, relapsed

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Actual)

8. Arms, Groups, and Interventions

Arm Title

dasatinib, rituximab, fludarabine

Arm Type

Other

Arm Description

Single-arm, open-label

Intervention Type

Drug

Intervention Name(s)

dasatinib

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Rituximab

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

fludarabine

Intervention Description

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

Primary Outcome Measure Information:

Title

Response Rate

Description

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)

Time Frame

2 years

Secondary Outcome Measure Information:

Title

Progression-Free and Overall Survival

Description

To describe the progression-free and overall surivial

Time Frame

2 years

Title

Toxicities

Description

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. 18 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 Exclusion Criteria: 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Philip Amrein, MD

Organizational Affiliation

Massachusetts General Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Massachusetts General Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

Facility Name

Beth Israel Deaconess Medical Center

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115

Country

United States

Facility Name

Dana-Farber Cancer Institute

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

I do not plan to share IPD.

Learn more about this trial

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

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