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Dose Escalation Study of Revlimid With Fludarabine-Rituximab for CLL/SLL

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ClinicalTrials.gov Identifier: NCT00543114
Recruitment Status : Terminated (lack of efficacy and tolerability)
First Posted : October 12, 2007
Last Update Posted : May 27, 2016
Information provided by (Responsible Party):

Study Description
Brief Summary:
The purpose of this study is to determine the safety of lenalidomide (revlimid) in combination with fludarabine and rituximab and to determine the highest dose of lenalidomide that can safely be given in that combination. Lenalidomide is a drug that alters the immune system and may also interfere with the the development of tiny blood vessels that help support tumor growth. Lenalidomide is approved by the FDA for the treatment of two different blood cancers called myelodysplastic syndrome and multiple myeloma. Lenalidomide has also been studied in subjects with relapsed CLL. In this research study we are adding lenalidomide to a well-established initial therapy for CLL/SLL.

Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Small Lymphocytic Leukemia Drug: Lenalidomide Drug: Fludarabine Drug: Rituximab Phase 1

Detailed Description:
  • Participants will be treated in groups (cohorts) of three to six subjects per cohort. The dose of lenalidomide or fludarabine will be increased from one cohort to the next. Regardless of the treatment cohort, participants will receive treatment in cycles lasting 28 days.
  • For the first 3-5 days (depending on the group), participants will be treated on an outpatient basis in the infusion room at the Dana-Farber Clinic, with fludarabine and rituximab. Fludarabine is given intravenously for 3-5 days. Rituximab is given intravenously on day 1 of each 28-day cycle. Lenalidomide is given orally once per day for 3 weeks, followed by 1 week of rest.
  • Participants will be monitored very closely during the study treatment. During the first 28 day period (cycle 1), a physical exam and routine blood tests will be performed weekly. All participants in a group must finish the first 28-day treatment period before we proceed with the next group. Once started on study treatment, participants will continue for six cycles (a cycle is 28 days) of combination therapy with all three drugs. During that period they will have a physical exam and routine blood tests on day 1 of each treatment cycle, and additional blood tests on day 15 of each cycle.
  • When participants complete 6 cycles of combination therapy, they will proceed with two additional months of the lenalidomide alone, for 21 out of 28 days.
  • Disease response will be evaluated after 2, 6, and 8 months of study treatment. The following tests and procedures will be performed: Physical exam; blood tests; CT scans to evaluate lymph nodes; skin testing; and bone marrow biopsy if all other tests show no evidence of any remaining CLL and if the baseline bone marrow biopsy was positive
  • Participants will have a physical exam and lab work every 3 months as long as their disease remains in remission.

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Dose Escalation Study of Lenalidomide (Revlimid) in Combination With Fludarabine-Rituximab (Rituxan) for Previously Untreated CLL/SLL
Study Start Date : October 2007
Primary Completion Date : June 2009
Study Completion Date : December 2012

Arms and Interventions

Arm Intervention/treatment
Experimental: Lenalidomide, fludarabine and rituximab
Lenalidomide-Dose level will depend upon time the participant enrolls on the study: Given orally once a day for 3 weeks followed by a one week rest period fludarabine- Dose level will vary depending upon when participant enters the trial: Given intravenously for 3-5 days Rituximab- Given intravenously on Day 1 of each 28 day cycle
Drug: Lenalidomide
Dose level will depend upon time the participant enrolls on the study: Given orally once a day for 3 weeks followed by a one week rest period
Other Name: Revlimid
Drug: Fludarabine
Dose level will vary depending upon when participant enters the trial: Given intravenously for 3-5 days
Drug: Rituximab
Given intravenously on Day 1 of each 28 day cycle

Outcome Measures

Primary Outcome Measures :
  1. To evaluate the safety of lenalidomide in combination with fludarabine-rituximab (FR) and to determine the maximum tolerated dose in subjects with previously untreated CLL/SLL. [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. To determine the objective response rate and progression-free survival following lenalidomide/FR in this patient population [ Time Frame: 2 years ]
  2. To determine the improvement in ORR following two months of consolidation lenalidomide after completion of combination therapy [ Time Frame: 2 years ]
  3. To assess effects on immune function as measured by cytokine levels, T and NK cell subsets, T cell activation during therapy and DTH vaccine responses. [ Time Frame: 2 years ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 18 years of age or older
  • Diagnosed with B-CLL/SLL based on the standard histologic and immunophenotypic criteria described in the WHO classification
  • No prior systemic therapy for CLL/SLL, including chemotherapy or antibody therapy
  • Currently needs therapy based on 1996 NCI-WG criteria
  • Measurable disease
  • ECOG Performance Status of 0-2
  • Laboratory test results within parameters outlined in protocol
  • Able to take aspirin daily as prophylactic anticoagulation

Exclusion Criteria:

  • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent document
  • Pregnant or breast-feeding females
  • Any condition, including the presence of abnormal laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
  • Use of any other experimental drug or therapy within 28 days of baseline
  • Known hypersensitivity to thalidomide
  • Development of erythema nodosum characterized by a desquamating rash while taking thalidomide or similar drugs
  • Prior use of lenalidomide
  • Concurrent use of other anti-cancer agents or treatments
  • Known positive for HIV
  • Chronic active Hep B patients not on prophylactic lamivudine
  • Diagnosis of Mantle Cell Lymphoma
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00543114

United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Massachusetts General Hospital
Beth Israel Deaconess Medical Center
Celgene Corporation
Principal Investigator: Jennifer R. Brown, MD, PhD Dana-Farber Cancer Institute
More Information

Responsible Party: Jennifer R. Brown, MD, PhD, Assistant Professor of Medicine, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00543114     History of Changes
Other Study ID Numbers: 07-097
First Posted: October 12, 2007    Key Record Dates
Last Update Posted: May 27, 2016
Last Verified: May 2016

Keywords provided by Jennifer R. Brown, MD, PhD, Dana-Farber Cancer Institute:

Additional relevant MeSH terms:
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Fludarabine phosphate
Antineoplastic Agents
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
Antimetabolites, Antineoplastic