Combination Therapy Using Lenalidomide (Revlimid)- Low Dose Dexamethasone and Rituximab for Treatment of Rituximab-Resistant, Non-Aggressive B-Cell Lymphomas

The recruitment status of this study is unknown because the information has not been verified recently.
Verified December 2011 by University of Pennsylvania.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT00783367
First received: October 30, 2008
Last updated: February 6, 2013
Last verified: December 2011
  Purpose

Pre-clinical data and recently published clinical data suggest a synergistic effect between lenalidomide and dexamethasone. We hypothesize that a combination of lenalidomide-dexamethasone can overcome rituximab resistance. To determine the response rate to lenalidomide and dexamethasone plus rituximab therapy in subjects with recurrent small B-cell non-Hodgkin lymphoma who have had lymphoma progression within 6 months of being treated with rituximab alone or with a rituximab-containing regimen, we propose initial treatment with both drugs for two 28-day treatment cycles (Part I). After response assessment following two cycles of lenalidomide-dexamethasone, patients will enter Part II of the study. In Part II, patients will receive lenalidomide-dexamethasone and rituximab to evaluate the potential reversal of rituximab resistance as measured by response to rituximab and progression-free survival following rituximab.


Condition Intervention Phase
Follicular Lymphoma
Marginal Zone B-Cell Lymphoma
MALT Lymphoma
Lymphoma of Mucosa-Associated Lymphoid Tissue
Lymphoma, Small Lymphocytic
Waldenstrom Macroglobulinemia
Mantle-Cell Lymphoma
Drug: lenalidomide-low dose dexamethasone plus rituximab
Drug: Lenalidomide + Rituximab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 2 Trial of Lenalidomide (Revlimid)-Dexamethasone + Rituximab in Recurrent Small B-Cell Non-Hodgkin Lymphomas (NHL) Resistant to Rituximab

Resource links provided by NLM:


Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:
  • Response rate to lenalidomide-dexamethasone + rituximab therapy in relapsed small B-cell lymphoma with rituximab resistance [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time until progression after lenalidomide-dexamethasone + rituximab therapy in relapsed small B-cell lymphomas with rituximab resistance [ Time Frame: twelve months ] [ Designated as safety issue: No ]
  • Compare the response rate for the previous rituximab-containing regimen to that obtained subsequently to lenalidomide-dexamethasone + rituximab therapy [ Time Frame: twelve months ] [ Designated as safety issue: No ]
  • Determine the toxicity profile of lenalidomide-dexamethasone + rituximab therapy in patients who have received a previous rituximab-containing combination regimen [ Time Frame: every twenty-eight days ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 25
Study Start Date: July 2008
Estimated Study Completion Date: August 2013
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: lenalidomide-low dose dexamethasone plus rituximab Drug: lenalidomide-low dose dexamethasone plus rituximab
Lenalidomide: 10mg capsules, orally, once daily for each 28 day cycle for the duration of the study; Dexamethasone: 8mg tablets, orally, once weekly on days 3, 10, 17, 24 of each 28 day cycle for the duration of the study; rituximab: 375mg/m2 IV (in the vein), once weekly on days 1, 8, 15, 22 during month 3 of therapy
Other Names:
  • Revlimid (lenalidomide)
  • Rituxan (rituximab)
  • Decadron (dexamethasone)
Drug: Lenalidomide + Rituximab
Other Name: Lenalidomide (Revlimid®) + Rituximab with and without Dexamethasone

  Eligibility

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

Inclusion Criteria:

  • Previously treated, histologically confirmed follicular lymphoma (grade 1, 2, 3a), marginal zone lymphoma, small lymphocytic lymphoma with less than <5000 lymphocytes/mm3 or lymphoplasmacytic lymphoma with <3g/mL IgM, mantle cell lymphoma by WHO classification
  • Flow cytometry or immunohistochemistry must document CD20 antigen expression. Past documentation of CD20 antigen expression is admissible.
  • Subjects must have been treated with rituximab in combination with chemotherapy or as monotherapy and must have refractory or progressive disease <6 months from the first rituximab dose of previous rituximab containing regimen
  • At least 18 years of age
  • ECOG performance status 0-2
  • Measurable disease must be present on physical examination or imaging studies. Any tumor mass >2cm is considered measurable.
  • Lesions that are considered non-measurable, but assessable include the following: bone lesions, ascites, pleural/pericardial effusion, lymphangitis cutis/pulmonis, bone marrow
  • Patients with a history of intravenous drug abuse or any behavior associated with increased risk of HIV infection should be tested for exposure to the HIV virus
  • Understand and voluntarily sign an informed consent
  • Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant of ASA may use warfarin or low molecular weight heparin)
  • Laboratory test results within these ranges: absolute neutrophil count greater than or equal to 1500/mm3; platelet count greater than or equal to 75,000/mm3; serum creatinine less than or equal to 2.0mg/dL; total bilirubin less than or equal to 1.5mg/dL (unless due to Gilbert's syndrome); AST (SGOT) and ALT (SGPT) less than or equal to 2.5 x ULN or less than or equal to 5 x ULN if hepatic metastases are present
  • Disease free of prior malignancies for greater than or equal to 5 years with the exception of currently treated basal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast
  • All study participants must be registered into the mandatory RevAssist program, and be willing and able to comply with the requirements of RevAssist
  • 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 prescribing lenalidomide (prescriptions must be filled within 7 days) 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.

Exclusion Criteria:

  • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from following study procedure
  • Pregnant or breast-feeding females
  • 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
  • Use of any other experimental drug or therapy within 28 days of baseline
  • Known hypersensitivity to thalidomide
  • The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs
  • Any prior use of lenalidomide
  • Known positivity for HIV or active infectious Hepatitis, type A, B, or C. Patients who test positive or who are known to be infected are not eligible due to an increased risk of infection with this regimen. HIV testing is not required for study entry, but is required if the patient is perceived to be at risk.
  • Known central nervous system involvement by lymphoma
  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: NCT00783367

Locations
United States, Pennsylvania
University of Pennsylvania; Abramson Cancer Center; Lymphoma Program
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
University of Pennsylvania
Celgene Corporation
Investigators
Principal Investigator: Stephen J Schuster, MD University of Pennsylvania
  More Information

Publications:

Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT00783367     History of Changes
Other Study ID Numbers: UPCC 02408, UPenn IRB#807684, RV-NHL-PI-0296
Study First Received: October 30, 2008
Last Updated: February 6, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Pennsylvania:
Revlimid
Celgene brand of lenalidomide
lenalidomide
Rituxan
CD20 antibody, rituximab
rituximab
Follicular Lymphoma
Marginal Zone B-Cell Lymphoma
Lymphoma, Small Lymphocytic
Waldenstrom Macroglobulinemia
Mantle-Cell Lymphoma
Antigens, CD20
refractory
resistantRefractory/progressive lymphoma less than 6 months from first rituximab dose of previous rituximab-containing regimen
Previously treated
Treated with rituximab

Additional relevant MeSH terms:
Lymphoma, Follicular
Lymphoma, Mantle-Cell
Lymphoma, B-Cell
Lymphoma, B-Cell, Marginal Zone
Waldenstrom Macroglobulinemia
Lymphoma
Lymphoma, Non-Hodgkin
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Leukemia, B-Cell
Leukemia, Lymphoid
Leukemia
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Rituximab
Lenalidomide

ClinicalTrials.gov processed this record on October 19, 2014