Multi-center Trial of Revlimid® and Rituximab for Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2010 by Chronic Lymphocytic Leukemia Research Consortium.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Celgene Corporation
Information provided by:
Chronic Lymphocytic Leukemia Research Consortium
ClinicalTrials.gov Identifier:
NCT01199575
First received: August 31, 2010
Last updated: September 9, 2010
Last verified: September 2010
  Purpose

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

Lenalidomide (Revlimid) is an immunomodulatory agent with promising clinical activity in CLL and is FDA approved for treatment of relapsed multiple myeloma and 5q-myelodysplastic syndrome. Rituximab (Rituxan) is a monoclonal antibody to CD20 that is approved for the treatment of CLL.

The primary objective of this study is to determine the overall response rate of the combination of Revlimid® and rituximab in previously treated CLL patients. All patients will receive treatment with Revlimid® starting at a low dose that will be 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.


Condition Intervention Phase
Chronic Lymphocytic Leukemia
CLL
Drug: Revlimid, rituximab
Drug: Relapsed or refractory CLL. Lenalidomide and Rituximab
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Two-Arm, Multi-center Trial of Revlimid® and Rituximab, for the Treatment of Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)

Resource links provided by NLM:


Further study details as provided by Chronic Lymphocytic Leukemia Research Consortium:

Primary Outcome Measures:
  • iwCLL working group response rate assessed after completion of 7 cycles of treatment. [ Time Frame: nine months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • adverse events to study treatment [ Time Frame: one year ] [ Designated as safety issue: Yes ]
  • progression free survival. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Conversion of MRD-positive complete response or partial response (PR) to a MRD-negative complete response (CR) or complete response (CR) respectively following an additional 6 cycles of Revlimid consolidation [ Time Frame: 13 cycles ] [ Designated as safety issue: No ]
  • changes in hematological parameters [ Time Frame: one year ] [ Designated as safety issue: No ]
  • Overall response in relationship to molecular and genetic prognostic factors [ Time Frame: 9 months ] [ Designated as safety issue: No ]
  • Chronic Lymphocytic Leukemia up-regulated protein 1 (CLLU1) [ Time Frame: two years ] [ Designated as safety issue: No ]
  • overall survival. [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • treatment free survival. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 80
Study Start Date: August 2010
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A: Subjects younger than 65 years old.

A: Lenalidomide starting at a low dose 2.5 or 5 mg, 21 days/cycle escalated based on patient tolerability. Rituximab at 375mg/m2 administered following the first 21 days of lenalidomide monotherapy, continued weekly throughout cycle 2, and then every 4 weeks for subsequent cycles (3-7). Each patient may receive up to 7 cycles of treatment with the combination lenalidomide/rituximab if no progressive disease or significant toxicity. Patients with residual disease can elect to receive 6 additional cycles of single agent Revlimid as consolidation.

Each patient may receive up to a maximum of 13 cycles of treatment if no progressive disease or significant toxicity.

Drug: Revlimid, rituximab
Drug:Lenalidomide and Rituximab Revlimid starting at a low dose and escalated based on patient tolerability 21 days of every cycle. Rituximab at 375mg/m2 administered following the first 21 days of Revlimid monotherapy, continued weekly throughout cycle 2, and then every monthly for subsequent cycles.Patients with residual disease, but without evidence of significant toxicity or progressive disease may stay on study for up to 6 additional cycles of single agent Revlimid. Each patient may receive up to a maximum of 13 cycles of treatment if no progressive disease or significant toxicity.
Other Names:
  • Chronic Lymphocytic Leukemia
  • Relapsed
  • Refractory
  • Revlimid(lenalidomide)
  • Rituximab (rituxan)
Experimental: B: Subjects age 65 years and older

B: Lenalidomide starting at a low dose 2.5 or 5 mg, 21 days/cycle and escalated based on patient tolerability. Rituximab at 375mg/m2 administered following the first 21 days of lenalidomide monotherapy, continued weekly throughout cycle 2, and then every 4 weeks for subsequent cycles (3-7). Each patient may receive up to 7 cycles of treatment with the combination lenalidomide/rituximab if no progressive disease or significant toxicity. Patients with residual disease can elect to receive 6 additional cycles of single agent Revlimid as consolidation.

Each patient may receive up to a maximum of 13 cycles of treatment if no progressive disease or significant toxicity.

Drug: Relapsed or refractory CLL. Lenalidomide and Rituximab
Drug:Lenalidomide and Rituximab Revlimid starting at a low dose and escalated based on patient tolerability 21 days of every cycle. Rituximab at 375mg/m2 administered following the first 21 days of Revlimid monotherapy, continued weekly throughout cycle 2, and then every monthly for subsequent cycles.Patients with residual disease, but without evidence of significant toxicity or progressive disease may stay on study for up to 6 additional cycles of single agent Revlimid. Each patient may receive up to a maximum of 13 cycles of treatment if no progressive disease or significant toxicity.
Other Names:
  • Chronic Lymphocytic Leukemia
  • Relapsed
  • Refractory
  • Revlimid(lenalidomide)
  • Rituximab (rituxan)

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 excluded.
  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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01199575

Contacts
Contact: Mary Carpenter, CRC 858-822-5635 mcarpenter@ucsd.edu
Contact: Danelle F James, MD 858-822-7894 dfjames@ucsd.edu

Locations
United States, California
University of California, San Diego Recruiting
La Jolla, California, United States, 92093
Contact: Mary Carpenter, CRC    858-822-5635    mcarpenter@ucsd.edu   
Contact: Alice K Vranceanu, Coordinator       avranceanu@ucsd.edu   
Principal Investigator: Danelle F James, MD         
Principal Investigator: Thomas Kipps, MD, PhD         
United States, Massachusetts
Dana Farber/Harvard Cancer Center at Dana farber Cancer Institute Not yet recruiting
Boston, Massachusetts, United States, 02115
Contact: Jennifer Brown, MD         
Contact: Kay Kehoe, Coordinator    617-582-8480    kekeho@partners.org   
Principal Investigator: Jennifer Brown, MD         
United States, New York
Long Island Jewish Medical Center Not yet recruiting
New Hyde Park, New York, United States, 11042
Contact: Kanti Rai, MD         
Contact: Nancy Driscoll, RPA-C    516-470-4050    Ndriscol@lij.edu   
Principal Investigator: Kanti Rai, MD         
United States, Ohio
Ohio state University Not yet recruiting
Columbus, Ohio, United States, 43210
Contact: Jeffrey Jones, MD         
Principal Investigator: Jeffrey Jones, MD         
Sponsors and Collaborators
Chronic Lymphocytic Leukemia Research Consortium
Celgene Corporation
Investigators
Study Director: Thomas J Kipps, MD, PhD Director of the CLL Research Consortium and University of California San Diego
Principal Investigator: Danelle F James, MD, MAS CLL Research Consortium and University of California San Diego
  More Information

Additional Information:
Publications:
Responsible Party: Danelle James, MD, MAS, University of California San Diego
ClinicalTrials.gov Identifier: NCT01199575     History of Changes
Other Study ID Numbers: CRC022
Study First Received: August 31, 2010
Last Updated: September 9, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by Chronic Lymphocytic Leukemia Research Consortium:
Chronic Lymphocytic Leukemia
CLL
Relapsed or Refractory
previously treated

Additional relevant MeSH terms:
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Rituximab
Lenalidomide
Thalidomide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Immunosuppressive Agents
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on September 18, 2014