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

NCT01373229 | Completed Phase 1 Results

• 2 other identifiers: Pro00026715RV0622
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Keywords

Chronic Lymphocytic Leukemia; CLL

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose

  4-16 months

Secondary Outcomes (5)

• Overall Response (Complete Response/Partial Response)

  at the end of 4 months of combination treatment and at 2 months after completion of therapy

• Progression-free Survival (PFS)

  time from day 1 of treatment to disease progression, death, or 2 years, whichever comes first

• Overall Survival (OS)

  the time from day 1 of treatment to death or 2 years, whichever comes first

• Reduction in Severity of B Symptoms

  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

• Reduction in the Frequency of Blood and Platelet Transfusions

  4 weeks prior to therapy and in the 4 weeks following the completion of therapy

Study Arms (1)

Lenalidomide + Plerixafor+ Rituximab

EXPERIMENTAL

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)

Interventions

Lenalidomide + Plerixafor (+ Rituximab) DRUG

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.

Also known as: Revlimid, Mozobil, Rituxan

Lenalidomide + Plerixafor+ Rituximab

Eligibility Criteria

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

You may qualify if:

• 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®.

You may not qualify if:

• 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).

Sponsors & Collaborators

• David Rizzieri, MD: lead
• Celgene Corporation: collaborator
• Genzyme, a Sanofi Company: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Lenalidomide; plerixafor; Rituximab

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)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Danielle Brander, MD
• Organization: Duke University Medical Center

danielle.brander@duke.edu

919-286-6897

Study Officials

• David A Rizzieri, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: June 12, 2011
• First Posted: June 14, 2011
• Study Start: January 1, 2012
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2015
• Last Updated: February 5, 2018
• Results First Posted: February 5, 2018

Record last verified: 2017-07

Locations

US (1)