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A Two-Arm, Multi-center Trial of Revlimid® and Rituximab, for the Treatment of Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)

Phase 2
18 Years
Open (Enrolling)
Chronic Lymphocytic Leukemia, CLL

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Trial Information

A Two-Arm, Multi-center Trial of Revlimid® and Rituximab, for the Treatment of Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)

The Chronic Lymphocytic Leukemia (CLL) Research Consortium (CRC) is conducting a two-arm,
multicenter phase II trial of Revlimid® and rituximab for Relapsed or Refractory Chronic
Lymphocytic Leukemia (CLL) for patients under the age of 65 and patients 65 years and older.

Revlimid® (lenalidomide) a derivative of thalidomide with immune-modulating properties.
Revlimid® is FDA approved for treatment of relapsed multiple myeloma and 5q- myelodysplastic
syndrome. Revlimid® has promising clinical activity, in both previously treated and
treatment naive CLL in early clinical trials. However, the mechanism(s) whereby Revlimid® is
active in CLL is unknown. Rituximab (Rituxan®) is a monoclonal antibody that binds to CD20
expressed on normal and leukemia B cells. Rituximab is approved for the treatment of CLL.

In preclinical models of lymphoma Revlimid improved the activity of Rituximab. In clinical
studies of relapsed and/or refractory CLL the combination Revlimid and Rituximab was
associated with better therapeutic effects compared with what was historically observed with
either agent alone.

The purpose of this study is to evaluate the safety and activity of the combination of
Revlimid® and rituximab in relapsed or refractory CLL, elucidate the mechanism of action of
Revlimid® in CLL, and to assess whether prognostic factors might predict those patients
likely to benefit from this therapy in the future.

The primary objective of this study is to determine the overall response rate (ORR) of the
combination of Revlimid® and rituximab in previously treated CLL patients for those age 65
years and above and those younger than 65.

Secondary objectives will evaluate the safety of the combination of Revlimid® and Rituximab,
response duration, improvement in hematologic parameters, activity of the combination in
high-risk CLL subsets, the significance of the tumor flare reaction and to compare the
activity of this regimen when administered to previously treated patients to our protocol in
the front line setting and to compare these outcomes for both arms of the study.

All patients will receive treatment with Revlimid® starting at a low dose that will be
slowly dose escalated based on individual patient tolerability. The combination of
Revlimid and Rituximab will be administered for a maximum of 7 cycles. Patients with
residual leukemia following seven cycles of treatment with the combination may elect to
continue on protocol for an additional 6 cycles of single agent Revlimid® consolidation.

All patients will have baseline assessment of known CLL prognostic factors through the CRC
tissue core. These known prognostic features in CLL together with novel prognostic factors
will be evaluated for the ability to predict response to treatment with Revlimid® and the
combination of Revlimid® and Rituximab.

Inclusion Criteria:

1. Diagnosis of chronic lymphocytic leukemia (CLL).

2. Subjects must have active disease appropriate for therapy.

3. Previous treatment for CLL

4. Understand and voluntarily sign an informed consent form.

5. Age ≥18 years at the time of signing the informed consent form.

6. Able to adhere to the study visit schedule and other protocol requirements.

7. ECOG performance status of ≤ 2 at study entry (see Appendix B).

8. Laboratory test results within these ranges: Absolute neutrophil count ≥ 1.0 x
109/L,Platelet count ≥ 50 x 109/L, Total bilirubin ≤ 1.5 mg/dL, AST (SGOT) and ALT
(SGPT) ≤ 2 x ULN, Creatinine clearance estimated to be ≥ 30 ml/min

9. Disease free of prior malignancies for ≥ 2 years with exception of currently treated
basal cell, squamous cell carcinoma of the skin, or carcinoma in situ" of the cervix
or breast.

10. Females of childbearing potential (FCBP)† must have a negative serum or urine
pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to
and again within 24 hours of starting Revlimid® and must either commit to continued
abstinence from heterosexual intercourse or begin TWO acceptable methods of birth
control, one highly effective method and one additional effective method AT THE SAME
TIME, at least 28 days before she starts taking Revlimid®. FCBP must also agree to
ongoing pregnancy testing. Men must agree to use a latex condom during sexual
contact with a FCBP even if they have had a successful vasectomy. All patients must
be counseled at a minimum of every 28 days about pregnancy precautions and risks of
fetal exposure. See Appendix: Risks of Fetal Exposure, Pregnancy Testing Guidelines
and Acceptable Birth Control Methods, AND also Appendix: Education and Counseling
Guidance Document.

Exclusion Criteria:

1. Known Hepatitis B Ag positive, Hepatitis C positive patients.

2. Known HIV positive patients.

3. Patients with uncontrolled Autoimmune Hemolytic Anemia (AIHA) or autoimmune
thrombocytopenia (ITP).

4. Inability to provide informed consent.

5. Concurrent malignancy (excluding basal and squamous cell skin cancers).

6. Active fungal, bacterial, and/or viral infection.

7. Any serious medical condition, laboratory abnormality, or psychiatric illness that
would prevent the subject from signing the informed consent form.

8. Pregnant or breast-feeding females. (Lactating females must agree not to breast feed
while taking Revlimid®).

9. Any condition, including the presence of laboratory abnormalities, which places the
subject at unacceptable risk if he/she were to participate in the study or confounds
the ability to interpret data from the study.

10. Use of any other experimental drug or therapy within 28 days of baseline.

11. Known hypersensitivity to thalidomide.

12. The development of erythema nodosum if characterized by a desquamating rash while
taking thalidomide or similar drugs.

13. Concurrent use of other anti-cancer agents or treatments.

14. Patients with history of deep venous thrombus or pulmonary embolism. Patients who are
at increased risk of thrombosis during treatment with Revlimid® including those
taking concurrent erythropoietin, darbepoetin or high-dose corticosteroids are also

15. Patients with a history of embolic events (e.g. TIA) from arrhythmia or peripheral
arterial disease or of recent mycocardial infarction whether or not treated with
anti-platelet drugs.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

iwCLL working group response rate assessed after completion of 7 cycles of treatment.

Outcome Time Frame:

nine months

Safety Issue:


Principal Investigator

Thomas J Kipps, MD, PhD

Investigator Role:

Study Director

Investigator Affiliation:

Director of the CLL Research Consortium and University of California San Diego


United States: Food and Drug Administration

Study ID:




Start Date:

August 2010

Completion Date:

June 2014

Related Keywords:

  • Chronic Lymphocytic Leukemia
  • CLL
  • Chronic Lymphocytic Leukemia
  • CLL
  • Relapsed or Refractory
  • previously treated
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid



Long Island Jewish Medical Center New Hyde Park, New York  11040
Ohio State University Columbus, Ohio  43210
University of California, San Diego La Jolla, California  92037-1709
Dana Farber/Harvard Cancer Center at Dana farber Cancer Institute Boston, Massachusetts  02115