A Phase 2 interventional study of Fludarabine, Cyclophosphamide, Rituximab, Lenalidomide in Chronic Lymphocytic Leukemia (CLL), sponsored by Hackensack Meridian Health. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-04-03.
Sponsored by Hackensack Meridian Health · Phase 2, Interventional, and Treatment
In previously-untreated subjects with CLL, fludarabine and rituximab with or without cyclophosphamide (FR or FCR) produces complete responses (CR) of 40-80%. The major complication of FCR has been grade 3/4 neutropenia which was reduced using a lower dose of fludarabine and cyclophosphamide (FCR-Lite) The objective of this study is to evaluate the minimal residual disease (MRD) complete response rate (using the 2008 IWCLL guidelines) after 4 cycles of FCR-Lite plus lenalidomide in subjects with previously untreated CLL. Lenalidomide is active in frontline treatment of CLL as well as in patients with refractory disease. MRD has been demonstrated to be a sensitive surrogate marker for progression-free survival. If patients are MRD negative complete responders (CR) they will stop at 4 cycles of FCR-Lite followed by the lenalidomide consolidation/maintenance arm of the study. If they have a MRD positive CR or partial response (PR) they will continue with 2 additional cycles of FCR-Lite plus lenalidomide followed by lenalidomide consolidation/maintenance. They will be re-tested for MRD after the 6th cycle of FCR-Lite and after 6 and 12 months of lenalidomide monotherapy If they have no response (NR) or progressive disease (PD) following 4 cycles of FCR-Lite plus lenalidomide they will be removed from the study.
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.
1,603 studies on the registry are indexed under Leukemia, Lymphocytic, Chronic, B-Cell; 243 are open to participants now.
This study's enrollment of 21 is below the median of 40 across 1,325 interventional studies indexed under Leukemia, Lymphocytic, Chronic, B-Cell.
Browse Leukemia, Lymphocytic, Chronic, B-Cell studies →Hackensack Meridian Health is the lead sponsor of 111 studies on the registry; 28 are open to participants now.
Of its 16 completed or terminated interventional studies of FDA-regulated products, 11 (69%) have results posted.
Counted across the registry records on this site, refreshed daily.
Patients must have diagnosis of CLL (as defined by the NCI Criteria below:
Patients must have phenotypically characterized CLL as defined as:
Exclusion Criteria:
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.
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.
Also known as: FCR + Lenalidomide
Complete Response
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.
Time frame: 28 day cycle, up to 4 cycles
Overall Response Rate
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.
Time frame: 28 day cycle, up to 6 cycles
| Milestone | FCR With Lenalidomide |
|---|---|
| Started | 21 |
| Completed | 12 |
| Not completed | 9 |
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.
| Percentage of Participants | FCR With Lenalidomide |
|---|---|
| Complete Response | 45 |
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.
| Percentage of Participants | FCR With Lenalidomide |
|---|---|
| Overall Response Rate | 95 |
Collected over From study enrollment to end of treatment, up to 18 months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| FCR With Lenalidomide | 1/21 (4.8%) | 9/21 (42.9%) | 19/21 (90.5%) |
| Event | FCR With Lenalidomide |
|---|---|
| Neutropenic FeverBlood and lymphatic system disorders | 3/21 |
| Maculopapular RashSkin and subcutaneous tissue disorders | 1/21 |
| FeverGeneral disorders | 1/21 |
| RashSkin and subcutaneous tissue disorders | 1/21 |
| SeizureNervous system disorders | 1/21 |
| Upper Respiratory InfectionRespiratory, thoracic and mediastinal disorders | 1/21 |
| Bilateral Leg WeaknessGeneral disorders | 1/21 |
| Event | FCR With Lenalidomide |
|---|---|
| NeutropeniaBlood and lymphatic system disorders | 19/21 |
| LeukopeniaBlood and lymphatic system disorders | 13/21 |
| HyperglycemiaBlood and lymphatic system disorders | 3/21 |
| AnemiaBlood and lymphatic system disorders | 1/21 |
| ThrombocytopeniaBlood and lymphatic system disorders | 1/21 |
| Infusion ReactionBlood and lymphatic system disorders | 1/21 |
| BacteremiaInfections and infestations | 1/21 |
| Pustular RashSkin and subcutaneous tissue disorders | 1/21 |
| Age, Continuous(years) | FCR With Lenalidomide |
|---|---|
| Median | 62.5 (42 to 75) |
| Sex: Female, Male(Participants) | FCR With Lenalidomide |
|---|---|
| Female | 9 |
| Male | 12 |
| Ethnicity (NIH/OMB)(Participants) | FCR With Lenalidomide |
|---|---|
| Hispanic or Latino | 0 |
| Not Hispanic or Latino | 21 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | FCR With Lenalidomide |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 2 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 0 |
| White | 18 |
| More than one race | 0 |
| Unknown or Not Reported | 1 |
| Region of Enrollment(participants) | FCR With Lenalidomide |
|---|---|
| United States | 21 |
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