Phase II Protocol for CLL With Fludarabine and Cyclophosphamide With Rituximab (FCR) Plus Lenalidomide (FCR)
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ClinicalTrials.gov Identifier: NCT01723839 |
Recruitment Status :
Completed
First Posted : November 8, 2012
Results First Posted : October 10, 2022
Last Update Posted : October 10, 2022
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Condition or disease | Intervention/treatment | Phase |
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Chronic Lymphocytic Leukemia (CLL) | Drug: Fludarabine, Cyclophosphamide, Rituximab, Lenalidomide | Phase 2 |
STUDY OBJECTIVES:
Primary:
The primary objective is to evaluate the complete response rate following 4 cycles of FCR-Lite plus lenalidomide in previously untreated patients with CLL.
Secondary:
The first secondary objective is to evaluate the toxicity of patients with previously untreated CLL treated with FCR-Lite plus lenalidomide, followed by lenalidomide. The second is to evaluate the overall response rate and overall survival of patients with previously untreated CLL treated with FCR-Lite plus lenalidomide followed by lenalidomide. The third is to determine whether adding lenalidomide as a consolidation/maintenance therapy will eliminate bone marrow minimal residual disease in CR patients and whether patients who have a PR after 6 cycles of FCR-Lite plus lenalidomide will respond to 12 months of lenalidomide. The final secondary objective is to determine whether the expression of ZAP-70, CD38, and chromosomes correlate with response rate, duration of response, and survival for previously untreated patients with CLL.
STUDY DESIGN:
2-stage phase 2 study-design. 19 subjects are treated in stage-1 with FCR-Lite plus 5mg lenalidomide increasing to 10mg and 15mg in subsequent cycles depending on toxicity. If there are at least 5 CRs the study will accrue an additional 35 subjects (see statistical section). A secondary objective of this study will be to determine if MRD positive patients will become MRD negative with lenalidomide consolidation/maintenance and whether PR patients will convert to CRs Lenalidomide will begin 2 months after the last dose of FCR-Lite in all subjects with CR. It may begin as soon as 1 month after FCR-Lite plus lenalidomide in subjects with PR. Lenalidomide is given in 28 d cycles increasing the dose from 5 mg/d to 10 mg/d in cycle 2 and to 15mg in cycles 3-6 if well- tolerated (no grade-3 or -4 toxicity). Patients with creatinine clearance ≥30ml/min and <60ml/min will start at 2.5mg daily increasing to 5 and 10mg in subsequent cycles . Reduction to the prior dose is allowed for grade-3/-4 toxicity. MRD will be studied by flow cytometry from bone marrow and peripheral blood samples following 4 and 6 cycles of FCR-Lite and after 6 and 12 months of lenalidomide in CR patients.
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 21 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Phase II Clinical Protocol for the Treatment of Patients With Previously Untreated CLL With Four or Six Cycles of Fludarabine and Cyclophosphamide With Rituximab (FCR) Plus Lenalidomide Followed by Lenalidomide Consolidation/ Maintenance |
Actual Study Start Date : | February 22, 2012 |
Actual Primary Completion Date : | June 8, 2021 |
Actual Study Completion Date : | June 8, 2021 |

Arm | Intervention/treatment |
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FCR with Lenalidomide
Fludarabine, Cyclophosphamide, Rituximab, Lenalidomide - 19 subjects are treated in stage-1 with FCR plus 5mg lenalidomide increasing to 10mg and 15mg in subsequent cycles depending on toxicity. If there are at least 5 CRs after 4 cycles of FCR plus lenalidomide the study will accrue an additional 35 subjects.
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Drug: Fludarabine, Cyclophosphamide, Rituximab, Lenalidomide
19 subjects are treated in stage-1 with FCR plus 5mg lenalidomide increasing to 10mg and 15mg in subsequent cycles depending on toxicity.
Other Name: FCR + Lenalidomide |
- Complete Response [ Time Frame: 28 day cycle, up to 4 cycles ]Analysis of the Primary Endpoint: The complete responses will be estimated by the number of patients with CR divided by the total number of evaluable patients.
- Overall Response Rate [ Time Frame: 28 day cycle, up to 6 cycles ]Analysis of the other Secondary Endpoints: The overall response rate will be estimated by the number of patients with complete and partial responses divided by the total number of evaluable patients.

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
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Patients must have diagnosis of CLL (as defined by the NCI Criteria below:
- Patients must have peripheral blood absolute lymphocyte count of >5,000/mm3 obtained within 2 weeks prior to start of study.
- The lymphocytosis must consist of small, mature lymphocytes, with ≤55% (not greater than 55%) prolymphocytes.
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Patients must have phenotypically characterized CLL as defined as:
- The predominant population of cells share B-cell antigens with CD5 in the absence of other pan-T-cell markers (CD3, CD2, etc.);
- Surface immunoglobulin (slg) and CD20 with low-cell surface density expression.
- If surface immunoglobulin can be demonstrated, the leukemic cells are restricted to expression of either kappa or lambda.
- Splenomegaly, hepatomegaly or lymphadenopathy are not required for the diagnosis of CLL
- Patients must require chemotherapy
- Patients must not have received prior treatment cytotoxic, immunotherapy or investigational therapy.
- Patients must not have history of corticosteroid treatment for CLL, Autoimmune thrombocytopenia, or autoimmune hemolytic anemia.
- Calculated creatinine clearance ≥30ml/min by Cockcroft-Gault formula
- Bilirubin must be ≤1.5mg/dl, unless secondary to tumor, obtained within 2 weeks prior to registration
- Platelets ≥75x109/L, unless due to CLL involvement of bone marrow
- Neutrophils ≥1.5x109/L, unless due to CLL involvement of bone marrow
- AST or ALT < 2x upper limit of normal, unless related to CLL
- Age ≥18 years
- ECOG performance status 0-2
- Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test
- Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy
- Able to take aspirin (81mg or 325mg) daily as prophylactic anticoagulation
- Subject must provide written informed consent
- All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®
Exclusion Criteria:
- Patients with autoimmune hemolytic anemia or autoimmune thrombocytopenia are not eligible
- No prior immunotherapy, investigational or cytotoxic chemotherapy
- Patients with a history of steroid treatment for CLL/SLL autoimmune hemolytic anemia, or autoimmune thrombocytopenia are not eligible
- Patients with active infections requiring oral or intravenous (IV) antibiotics until resolution of the infection and completion of therapeutic antibiotics
- Women of childbearing potential and sexually active males who both refuse to use an accepted and effective method of contraception or women who are breastfeeding
- Patients with a second malignancy other than basal cell carcinoma or squamous cell carcinoma of the skin or in situ carcinoma of the cervix are not eligible unless the tumor was treated with curative intent at least two years previously
- History of known HIV
- History or presence CNS disease
- Evidence of laboratory TLS by Cairo-Bishop definition of Tumor Lysis Syndrome
- History of corticosteroid treatment for CLL, Autoimmune thrombocytopenia, or autoimmune hemolytic anemia.

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): NCT01723839
United States, New Jersey | |
John Theurer Cancer Center at HackensackUMC | |
Hackensack, New Jersey, United States, 07601 |
Principal Investigator: | Andre Goy, MD | John Theurer Cancer Center at HackensackUMC |
Documents provided by Hackensack Meridian Health:
Responsible Party: | Hackensack Meridian Health |
ClinicalTrials.gov Identifier: | NCT01723839 |
Other Study ID Numbers: |
Pro00002262 RV-CLL-PI-0530 |
First Posted: | November 8, 2012 Key Record Dates |
Results First Posted: | October 10, 2022 |
Last Update Posted: | October 10, 2022 |
Last Verified: | October 2022 |
CLL FCR Rituximab Lenalidomide Cyclophosphamide |
Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Lymphoid Leukemia Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Leukemia, B-Cell Cyclophosphamide Rituximab Fludarabine Lenalidomide |
Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Antineoplastic Agents, Immunological Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Growth Inhibitors |