A Phase I Trial Using Cyclophosphamide, Rituximab and Revlimid (CR2) for the Treatment of Relapsed/Refractory B-Cell Chronic Lymphocytic Leukemia (B-CLL) and Small Lymphocytic Lymphoma (SLL)

This study has been terminated.
(Slow Accrual)
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Rajni Sinha, Emory University
ClinicalTrials.gov Identifier:
NCT01005979
First received: September 30, 2009
Last updated: February 28, 2013
Last verified: February 2013
  Purpose

The purpose of this study is to determine the maximum tolerated dose (MTD), safety and toxicity when cyclophosphamide, rituximab and lenalidomide (Revlimid) are combined for the treatment of relapsed/refractory of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).


Condition Intervention Phase
Leukemia, Lymphocytic, Chronic, B-Cell
Chronic Lymphocytic Leukemia
Lymphoma, Small Lymphocytic
Drug: Lenalidomide, Rituximab, and Cyclophosphamide
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Trial Using Cyclophosphamide, Rituximab and Revlimid (CR2) for the Treatment of Relapsed/Refractory B-Cell Chronic Lymphocytic Leukemia (B-CLL) and SLL

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • The primary endpoint is to determine the maximum tolerated dose of lenalidomide in combination with cyclophosphamide and rituximab for the treatment of CLL or SLL. [ Time Frame: Day 28 of the first cycle of chemotherapy ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Assess response criteria, including complete response rate, survival at 1 year, time to progression, duration of response, and eradication of minimal residual disease. [ Time Frame: Response will be measured after 4 cycles, at the end of treatment and then every 3 months post treatment. ] [ Designated as safety issue: No ]

Enrollment: 6
Study Start Date: July 2010
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A Drug: Lenalidomide, Rituximab, and Cyclophosphamide

COHORT 1: Cyclophosphamide 250 mg/m2 day 1, 2 and 3, Rituximab 500 mg/m2 i.v. day 1, Lenalidomide 2.5 mg/day starting day 8-28 of Cycle 1 and then daily on Days 1-28 of subsequent cycles

COHORT 2: Cyclophosphamide 250mg/m2 day 1, 2 and 3. Rituximab 500 mg.m2 i.v. daY Lenalidomide 5 mg/day starting day 8 -28 of Cycle 1 and then daily on Days 1-28 of subsequent cycles

COHORT 3: Cyclophosphamide 250mg/m2 day 1, 2 and 3, Rituximab 500 mg.m2 i.v. day 1, Lenalidomide 10 mg/day starting day 8 -28 of Cycle 1 and then daily on Days 1-28 of subsequent cycles

COHORT 4: Cyclophosphamide 250mg/m2 day 1, 2 and 3, Rituximab 500 mg.m2 i.v. day 1, Lenalidomide 15 mg/day starting day 8 -28 of Cycle 1 and then daily on Days 1-28 of subsequent cycles

Patients will receive a total of 6-8 cycles.

Other Names:
  • Revlimid
  • Rituxan
  • Mab Thera
  • Endoxan
  • Cytoxan
  • Neosar
  • Procytox
  • Revimmune

  Eligibility

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

Inclusion Criteria:

  1. Understand and voluntarily sign an informed consent form.
  2. Age ≥ 18 years at the time of signing the informed consent form.
  3. Able to adhere to the study visit schedule and other protocol requirements.
  4. Relapsed/refractory B-cell CLL or SLL
  5. All previous cancer therapy, including radiation, hormonal therapy and surgery, must have been discontinued at least 2 weeks prior to treatment in this study.
  6. Patients must have received at least one prior therapy and must meet the NCI Working Group (NCI WG) Criteria for treatment of B-CLL as described in Appendix D.
  7. ECOG performance status of ≤ 2 at study entry (see Appendix C).
  8. Laboratory test results within these ranges (unless related to CLL involvement):

    • Absolute neutrophil count ≥ 1000 /mm3
    • Platelet count ≥ 50,000/mm³
    • Serum creatinine ≤ 1.5 mg/dL. Serum creatinine > 1.5 mg/dL requires creatinine clearance of ≥ 60 mL/min by Cockroft-Gault formula.
    • Total bilirubin ≤ 1.5 mg/dL
    • AST (SGOT) and ALT (SGPT) ≤ 2 x ULN or ≤ 5 x ULN if hepatic metastases are present.
  9. Disease free of second malignancies for ≥ 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "insitu" 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 lenalidomide 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 lenalidomide. 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 A: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods, AND also Appendix B: Education and Counseling Guidance Document.
  11. Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin).

Exclusion Criteria:

  1. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
  2. Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
  3. 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.
  4. Evidence of laboratory TLS by Cairo-Bishop criteria (Appendix J) (subjects may be enrolled upon correction of electrolyte abnormalities).
  5. Use of any other experimental drug or therapy within 28 days of baseline.
  6. Known hypersensitivity to thalidomide.
  7. The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
  8. Any prior use of lenalidomide.
  9. Concurrent use of other anti-cancer agents or treatments.
  10. Known positive for HIV or infectious hepatitis, type A, B or C.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01005979

Locations
United States, Georgia
Emory University Winship Cancer Institute
Atlanta, Georgia, United States, 30322
Sponsors and Collaborators
Emory University
Celgene Corporation
Investigators
Principal Investigator: Rajni Sinha, MD Emory University Winship Cancer Institute
  More Information

No publications provided

Responsible Party: Rajni Sinha, Principal Investigator, Emory University
ClinicalTrials.gov Identifier: NCT01005979     History of Changes
Other Study ID Numbers: WCI1642-09
Study First Received: September 30, 2009
Last Updated: February 28, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Emory University:
Leukemia, Lymphocytic, Chronic, B-Cell
Chronic Lymphocytic Leukemia
Lymphoma, Small Lymphocytic
Lymphoma
Leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Rituximab
Lenalidomide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on April 17, 2014