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Lenalidomide + Plerixafor in Previously Treated Chronic Lymphocytic Leukemia (CLL)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Celgene Corporation
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
David Rizzieri, MD, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT01373229
First received: June 12, 2011
Last updated: March 25, 2014
Last verified: March 2014
  Purpose

In research studies, lenalidomide (also called Revlimid) has shown some response in chronic lymphocytic leukemia (CLL); however, responses are usually partial responses that occur after several months of taking the study drug. It is thought that by adding the drug plerixafor (also called Mozobil) responses may be improved and/or occur sooner.

The main purpose of this study is to determine the dose of plerixafor that is safe to use in combination with lenalidomide. The study will also look at the response rates of the combination of lenalidomide and plerixafor and the effect the study drugs have on CLL cells.


Condition Intervention Phase
Leukemia, Lymphocytic, Chronic, B-Cell
Drug: Lenalidomide + Plerixafor (+ Rituximab)
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Lenalidomide in Combination With Plerixafor in Patients With Previously Treated Chronic Lymphocytic Leukemia

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Maximum Tolerated Dose [ Time Frame: 4-16 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Response (CR/PR) [ Time Frame: at the end of 4 months of combination treatment and at 2 months after completion of therapy ] [ Designated as safety issue: No ]
  • Progression-free survival (PFS) [ Time Frame: time from day 1 of treatment to disease progression, death, or 2 years, whichever comes first ] [ Designated as safety issue: No ]
  • Overall survival (OS) [ Time Frame: the time from day 1 of treatment to death or 2 years, whichever comes first ] [ Designated as safety issue: No ]
  • Reduction in severity of B symptoms [ Time Frame: at the end of stage 1 (lenalidomide alone), at the end of stage 2 (4 months of combination), and at 2 months post-completion of therapy ] [ Designated as safety issue: No ]
    Reduction in the severity of the following B symptoms will be assessed: fever ≥ 101F, chills, night sweats, and anorexia with weight loss.

  • Reduction in the frequency of blood and platelet transfusions [ Time Frame: 4 weeks prior to therapy and in the 4 weeks following the completion of therapy ] [ Designated as safety issue: No ]
    The change in number of transfusions from pre- to post-treatment will be calculated and summarized across all patients by giving the minimum, the 25th, 50th (median) and the 75th percentile and the maximum.

  • Reduction in the number of B-symptoms [ Time Frame: at the end of stage 1 (lenalidomide alone), at the end of stage 2 (4 months of combination), and at 2 months post-completion of therapy ] [ Designated as safety issue: No ]

Enrollment: 21
Study Start Date: January 2012
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lenalidomide + Plerixafor+ Rituximab
  1. Lenalidomide 5mg by mouth (PO) daily beginning cycle 1 day 1.
  2. Stage 1: increase by 2.5mg every 7 days to a maximum dose of 10mg.
  3. Stage 2: plerixafor will be added after 28 days of 10mg dose maintenance and white blood cell count (WBC) <100.0 x 109 / L.
  4. Dose cohorts of escalating subcutaneous (SC) thrice weekly plerixafor with continuous 10mg lenalidomide:

    • Cohort 1: 0.24 mg/kg
    • Cohort 2: 0.32 mg/kg
    • Cohort 3: 0.42 mg/kg
    • Cohort 4: 0.54 mg/kg
  5. Stage 3: Rituximab 375mg/m2 will be added on day 1 of cycles 5-12, day 1 of combination therapy for subjects with PR.
  6. Subjects will then continue single agent lenalidomide until disease progression.
Drug: Lenalidomide + Plerixafor (+ Rituximab)
  1. Lenalidomide 5mg by mouth (PO) daily beginning cycle 1 day 1.
  2. Stage 1: increase by 2.5mg every 7 days to a maximum dose of 10mg.
  3. Stage 2: plerixafor will be added after 28 days of 10mg dose maintenance and white blood cell count (WBC) <100.0 x 109 / L.
  4. Dose cohorts of escalating subcutaneous (SC) thrice weekly plerixafor with continuous 10mg lenalidomide:

    • Cohort 1: 0.24 mg/kg
    • Cohort 2: 0.32 mg/kg
    • Cohort 3: 0.42 mg/kg
    • Cohort 4: 0.54 mg/kg
  5. Stage 3: Rituximab 375mg/m2 will be added on day 1 of cycles 5-12, day 1 of combination therapy for subjects with PR.
  6. Subjects will then continue single agent lenalidomide until disease progression.
Other Names:
  • Revlimid
  • Mozobil
  • Rituxan

Detailed Description:

The combination of lenalidomide and plerixafor will be evaluated in this single institution, open label clinical study of subjects with relapsed chronic lymphocytic leukemia (CLL). The overall design of the phase 1 study includes up to three treatment "stages."

Each subject will receive lenalidomide 5mg by mouth daily beginning on cycle 1 day 1. If tolerated, the dose will be increased by 2.5mg every 7 days to a maximum dose of 10mg by mouth daily (Stage 1). Once the subject is stably maintained on a daily dose of lenalidomide of 10mg daily and the white blood cell (WBC) count is <100.0 x 109 / L, and has been taking lenalidomide for at least 28 days, plerixafor will be added (Stage 2). In the dose escalation phase, 4 different doses of plerixafor in combination with lenalidomide will be studied in cohorts of 3 to 6 subjects each, following a standard "3 + 3" format:

  • Cohort 1: plerixafor 0.24 mg/kg subcutaneous (SC) daily thrice weekly (Mon, Wed, Fri)
  • Cohort 2: plerixafor 0.32 mg/kg SC daily thrice weekly (Mon, Wed, Fri)
  • Cohort 3: plerixafor 0.42 mg/kg SC daily thrice weekly (Mon, Wed, Fri)
  • Cohort 4: plerixafor 0.54 mg/kg SC daily thrice weekly (Mon, Wed, Fri) Plerixafor will be administered for 3 weeks of each cycle (days 1, 3, 5, 8, 10, 12, 15, 17, and 19) followed by a 1 week rest period. Lenalidomide dosing will be continuous.

An interim assessment of response will be performed after 4 cycles of combination therapy:

  • Subjects achieving a complete response (CR) by National Cancer Institute (NCI)-96 criteria will continue lenalidomide monotherapy (plerixafor is discontinued) until disease progression.
  • Subjects achieving a partial response (PR) will continue both lenalidomide and plerixafor. Additionally, rituximab 375mg/m2 will be added on day 1 of each subsequent cycle beginning with cycle 5, day 1 of combination therapy. (Stage 3). Treatment with the combination of lenalidomide and plerixafor will continue for a maximum of 12 cycles of combination therapy. Subjects may receive up to 8 doses of rituximab concurrent with lenalidomide and plerixafor on day 1 of each cycle. Subjects will then continue single agent lenalidomide until disease progression.
  • Subjects with stable disease may continue lenalidomide and plerixafor at the discretion of the investigator and the subject. Rituximab 375 mg/m2 will be added on day 1 of each subsequent cycle. Treatment, dose, schedule, and duration are the same as for subjects achieving a PR.
  Eligibility

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

Inclusion Criteria:

  • Histologically confirmed diagnosis of chronic lymphocytic leukemia (CLL) or Small lymphocytic lymphoma (SLL) as established by the National Cancer Institute (NCI) Working Group Response Criteria (NCI 96 Criteria).
  • Received one or more prior therapies for CLL.
  • Subjects must have symptomatic disease requiring therapy as defined by the protocol.
  • >/= 4 weeks from prior cancer therapy.
  • Eastern Cooperative Oncology Group (ECOG) performance status of </= 2.
  • All study subjects must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.

Exclusion Criteria:

  • Prolymphocytic leukemia (PLL).
  • Richter's (large cell) transformation.
  • Prior allogeneic transplant within 12 months or prior allogeneic transplant > 12 months currently receiving immunosuppressants.
  • Active autoimmune hemolytic anemia.
  • Central nervous system (CNS) involvement.
  • Chronic enteral corticosteroids > 10mg prednisone or equivalent.
  • Evidence of laboratory tumor lysis syndrome (TLS) by Cairo-Bishop Definition of Tumor Lysis Syndrome
  • Use of any other experimental drug or therapy within 28 days of baseline
  • Major surgery 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 seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV).
  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: NCT01373229

Locations
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
David Rizzieri, MD
Celgene Corporation
Genzyme, a Sanofi Company
Investigators
Study Director: Mark Lanasa, MD, PhD Unafilliated
Principal Investigator: David A Rizzieri, MD Duke University
  More Information

No publications provided

Responsible Party: David Rizzieri, MD, Associate Professor of Medicine, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT01373229     History of Changes
Other Study ID Numbers: Pro00026715, RV0622
Study First Received: June 12, 2011
Last Updated: March 25, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Duke University:
Chronic Lymphocytic Leukemia
CLL

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
JM 3100
Lenalidomide
Rituximab
Thalidomide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antineoplastic Agents
Antirheumatic Agents
Antiviral Agents
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Leprostatic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 25, 2014