Phase II Protocol for CLL With Fludarabine and Cyclophosphamide With Rituximab (FCR) Plus Lenalidomide

NCT01723839 | Completed Phase 2 Results DMC

• 1 other identifier: Pro00002262 RV-CLL-PI-0530
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Chronic Lymphocytic Leukemia (CLL)

Keywords

CLL; FCR; Rituximab; Lenalidomide; Cyclophosphamide

Outcome Measures

Primary Outcomes (1)

• 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.

  28 day cycle, up to 4 cycles

Secondary Outcomes (1)

• Overall Response Rate

  28 day cycle, up to 6 cycles

Study Arms (1)

FCR with Lenalidomide

OTHER

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

Interventions

Fludarabine, Cyclophosphamide, Rituximab, Lenalidomide DRUG

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

FCR with Lenalidomide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hackensack Meridian Health: lead
• Celgene Corporation: collaborator

Study Sites (1)

John Theurer Cancer Center at HackensackUMC

Hackensack, New Jersey, 07601, United States

Location

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  BACKGROUND

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

fludarabine; Cyclophosphamide; Rituximab; Lenalidomide; Receptors, Fc

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins

Results Point of Contact

• Title: Joshua Zenreich
• Organization: John Theurer Cancer Center at Hackensack Meridian Health

joshua.zenreich@hmhn.org

551-996-4248

Study Officials

• Andre Goy, MD

  John Theurer Cancer Center at HackensackUMC

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2012
• First Posted: November 8, 2012
• Study Start: February 22, 2012
• Primary Completion: June 8, 2021
• Study Completion: June 8, 2021
• Last Updated: October 10, 2022
• Results First Posted: October 10, 2022

Record last verified: 2022-10

Locations

US (1)