Lenalidomide in Comb w/Rituximab for Pts w/CD5+/CD20+ Hem Malignancies Who Relapse/Progress After Rituximab

NCT00609869 | Completed Phase 2 Results

• 2 other identifiers: MCC-14978RV-CLL-PI-067
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this research is to evaluate the use of Rituximab in combination with Revlimid in the treatment of refractory Mantle Cell Lymphoma (MCL) and Chronic Lymphocytic Leukemia (CLL). Revlimid® is a drug that changes the immune system and it may also get in the way with the growth of tiny blood vessels that help support tumor growth. Therefore, in theory, it may reduce or prevent the growth of cancer cells. Revlimid® is approved by the Food and Drug Administration (FDA) for the treatment of specific types of Myelodysplasia syndrome (MDS) and Multiple Myeloma, two different types of blood cancer. It is currently being tested in a variety of cancer conditions. In this case it is considered experimental.

Conditions

Lymphocytic Leukemia; Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  The sum of Complete Remission (CR) plus Partial Remission (PR) rates. Duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, and must be confirmed greater than 8 weeks after first meeting CR or PR criteria. Response and progression for Chronic Lymphocytic Leukemia (CLL) were evaluated using 2008 updated National Cancer Institute-Sponsored Working Group Guidelines (NCI-WG) for Chronic Lymphocytic Leukemia. CR: all of the criteria must be met, and patients have the lack disease-related constitutional symptoms: PR: at least two of the criteria of Group A plus one of the criteria of group B have to be met. Group A Parameters: Lymphadenopathy; Hepatomegaly; Splenomegaly; Blood; Lymphocytes; Marrow. Group B Parameters: Platelet count; Hemoglobin; Neutrophils.

  Up to 6 years

Secondary Outcomes (2)

• Clinical Benefit Rate

  Up to 6 years

• Median Time to Treatment Failure (TTF)

  Up to 6 years

Study Arms (1)

Lenalidomide and Rituximab

EXPERIMENTAL

28 day cycles of Lenalidomide administered orally and Rituximab administered intravenously. Lenalidomide: Escalating doses starting with of 2.5 mg daily on 28-days cycles. Rituximab: at 375 mg/m\^2 on a weekly basis for the first cycle starting on day 15.

Drug: Lenalidomide; Drug: Rituximab

Interventions

Lenalidomide DRUG

Lenalidomide was administered orally with escalating doses on 28-days cycles. The first cycle was administered with a starting dose of 2.5 mg daily on days 1-7, 5mg on days 8-14 and 10 mg on days 15-21, followed by seven days off. On cycle 2 and beyond lenalidomide was administered at 20 mg daily on days 1-21.

Also known as: REVLIMID®

Lenalidomide and Rituximab

Rituximab DRUG

Rituximab was administered at 375 mg/m\^2 intravenously on a weekly basis for the first cycle starting on day 15. Subsequent rituximab doses were administered on day one of cycle 2 and beyond, every 4 weeks. Doses were repeated on 28-day cycles until disease progression or unacceptable toxicity, but were planned for 12 cycles.

Also known as: RITUXAN®

Lenalidomide and Rituximab

Eligibility Criteria

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

You may qualify if:

• Have histologically or cytologically confirmed CD5+/CD20+ B-Cell Chronic Lymphocytic Leukemia or Mantle Cell Lymphoma
• Meet the following CLL criteria to participate in this study:
• Absolute lymphocyte count \> 5000/μL
• CD20+ and CD5+
• Atypical cells representing \< 55% on the peripheral smear
• Bone marrow lymphocytes ≥ 30%
• Or previous confirmed diagnosis of CLL/small lymphocytic lymphoma (SLL) with less than 5000/μl or less than 30% lymphocytes in BM
• CLL Patients are eligible if they have stage III or IV disease. Patients with stage 0, I or II disease will be eligible if they have evidence of active disease defined as one or more of the following signs/symptoms:
• Documented weight loss of ≥ 10% over a six month period
• Febrile episodes of 38 degrees Celsius (100.5 degrees F) or greater for greater than 2 weeks without evidence of infection
• Massive or progressive splenomegaly defined as \> 6 cm below the left costal margin
• Massive (\> 10 cm in longest diameter) or progressive lymphadenopathy
• Patients with progressive lymphadenopathy will need a biopsy of the lymphadenopathy within the previous six months to ensure that the disease entity remains chronic lymphocytic leukemia. Lymph node biopsy can be deferred if the patient does not have superficial lymphadenopathy that is easily accessible by surgery or by CT guided biopsy.
• The diagnosis of MCL is based upon the National Comprehensive Cancer Network (NCCN) guidelines. The patient's will have biopsy proven CD5+/CD20+/CD23- mantle cell lymphoma with the characteristic cytogenetic abnormality t(11;14) or a cyclin D1 positive immunophenotype. If malignancy is CD23+ but FISH positive for t(11;14), diagnosis of mantle cell lymphoma can be made. Patients with mantle cell lymphoma require appropriate staging which would include upper and lower endoscopy within 2 months of enrollment per NCCN guidelines without additional treatment since the endoscopies.
• Patients with MCL and CLL will be eligible if they have relapsed or progressive disease after Rituximab therapy or a combination therapy including Rituximab. Any other number of previous treatments is allowed including autologous or allogeneic bone marrow transplantation. Patients who are younger than age 65 who have not had a bone marrow transplant must be ineligible or have declined a bone marrow (BM) transplant to participate in this study. Although a transplant is not the standard of care for this patient population, it does provide the best opportunity for a cure.

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
• May not be receiving any other investigational agents
• Known brain metastases
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to lenalidomide and/or thalidomide
• Prior desquamating (blistering) rash with thalidomide
• Neuropathy ≥ grade 2
• Uncontrolled intercurrent illness including (not limited to) ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, psychiatric illness/social situations that would limit compliance with study requirements.
• Women currently pregnant or breastfeeding
• Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine are eligible.
• History of another malignancy besides CLL or MCL who have been disease-free ≤ 3 years with exception of basal cell or squamous cell carcinoma of skin or carcinoma in situ of cervix or breast
• Any serious medical condition or psychiatric illness that will prevent patient from signing the informed consent form or will place the patient at unacceptable risk if he/she participates in the study
• Prior use of lenalidomide
• Prior severe hypersensitivity to Rituximab or other murine products

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Celgene Corporation: collaborator

Study Sites (2)

Center for Cancer Care & Research/Watson

Lakeland, Florida, 33805, United States

Location

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphoid; Lymphoma, Mantle-Cell

Interventions

Lenalidomide; Rituximab

Condition Hierarchy (Ancestors)

Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Lymphoma

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

Limitations and Caveats

The 4 Mantle Cell participants were not evaluated for Outcome Measures due to their low enrollment.

Results Point of Contact

• Title: Javier Pinilla-Ibarz
• Organization: H. Lee Moffitt Cancer Center and Research Institute

javier.pinilla@moffitt.org

813-745-1387

Study Officials

• Javier Pinilla, M.D., PhD.

  H. Lee Moffitt Cancer Center and Research Institute

  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: January 24, 2008
• First Posted: February 7, 2008
• Study Start: October 1, 2007
• Primary Completion: February 1, 2014
• Study Completion: August 1, 2015
• Last Updated: September 17, 2015
• Results First Posted: September 1, 2014

Record last verified: 2015-09

Locations

US (2)