Fludarabine, Rituximab, and Lenalidomide in Minimally Treated/Untreated Patients With Chronic Lymphocytic Leukemia (CLL)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Celgene Corporation
Genentech
Information provided by (Responsible Party):
SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier:
NCT00536341
First received: September 24, 2007
Last updated: April 9, 2014
Last verified: April 2014
  Purpose

This phase I/II trial will combine fludarabine, rituximab, and lenalidomide in untreated or minimally treated (Phase I only) CLL patients, employing fixed doses of fludarabine and rituximab, using a schedule similar to that examined by the investigators at MD Anderson. Given that the optimal dose and schedule is not currently known, this trial will perform a phase I component followed by a phase II examination to further explore this regimen's activity.


Condition Intervention Phase
Chronic Lymphocytic Leukemia
Drug: lenalidomide, fludarabine, rituximab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Fludarabine, Rituximab, and Lenalidomide in Minimally Treated and Untreated Patients With Chronic Lymphocytic Leukemia

Resource links provided by NLM:


Further study details as provided by SCRI Development Innovations, LLC:

Primary Outcome Measures:
  • Safety and tolerability [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]

Enrollment: 64
Study Start Date: January 2008
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: lenalidomide, fludarabine, rituximab Drug: lenalidomide, fludarabine, rituximab

Phase I Non-stratified, dose-escalation: >=3 patients per dose level. Safety and tolerability will be evaluated every 2 weeks during the active treatment. Doses of lenalidomide will be escalated, while the fludarabine and rituximab doses remain fixed.

Phase II The Phase II regimen will be chosen following a review of the Phase I data. Following selection of the Phase II schedule, 40 treatment naive patients will be enrolled and treated with the Phase II regimen every 28 days for up to 6 courses. For those patients achieving a CR after 3 cycles, one additional cycle of treatment will be administered beyond CR confirmation.


Detailed Description:

Primary (Phase I) Portion:

  1. To determine the overall safety and tolerability of this regimen and to define the optimal phase II dosing schedule.
  2. To determine the dose limiting toxicity (DLT) and the maximum tolerated dose (MTD) of lenalidomide when combined with a 3 day course of fludarabine and monthly rituximab.

Primary (Phase II) Portion:

  1. To determine the complete response (CR) rate.
  2. To determine minimal residual disease by flow cytometry in patients who otherwise meet CR criteria and correlate with progression free and overall survival.

Secondary (Phase II) Portion:

  1. To determine partial remission and overall response rate.
  2. To measure progression free survival, overall survival, and response duration.
  3. To correlate responses with: RAI stage, degree of white blood cell count elevation, CD 38 expression levels, FISH for 11q deletion, 17p deletion, 13q deletion, and trisomy 12, and beta-2 microglobulin.
  4. To determine the effects of therapy on the patient's absolute CD4 count and IgG, IgA, and IgM levels 2 months post-treatment and 1 year after the completion of therapy compared to baseline levels.
  Eligibility

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

Inclusion Criteria:

  • Understand and voluntarily sign an informed consent form.
  • Able to adhere to the study visit schedule and other protocol requirements.
  • Age >=18 years at the time of signing the informed consent form.
  • Patient must have histopathologically confirmed B-cell CLL
  • For Phase I only: Untreated or minimally treated patients (patients who have received only prior single agent rituximab) are eligible. For those patients who have had rituximab monotherapy, last dose must be greater than 90 days prior to beginning study treatment.
  • For Phase II only: Untreated B-cell CLL patients only.
  • Rai staging, will be employed. Patients must have Rai stage III/IV disease (irrespective of symptoms) OR symptomatic Rai stage 0-II disease, requiring therapy as defined by NCI 1996 guidelines.
  • Platelets must be > 75,000/mm3 and absolute neutrophil count must be > 1000/mm3 within 14 days of starting protocol treatment unless treating physicians deems the neutropenia is related to marrow involvement and then ANC > 750/mm3 is allowed.
  • Serum creatinine <=2.0 mg/dl obtained within 14 days of starting protocol treatment. Creatinine clearance as determined by the Cockroft-Gault formula, using ideal body weight, must be > 30 mL/minute.
  • AST or ALT must be < 3 x the upper limit of normal within 14 days of starting treatment.
  • ECOG performance of 0, 1 or 2.
  • Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.
  • Disease free of prior malignancies for >= 2 years (including carcinoma in situ of the cervix or breast) treated with curative intent and anticipated 5 year disease-free survival is greater than 90%. Any basal cell or squamous cell carcinoma of the skin treated with curative intent is permitted.
  • Able to take aspirin (325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use low molecular weight heparin).

Exclusion Criteria:

  • Major surgery less than 28 days prior to study treatment.
  • Any prior use of lenalidomide or thalidomide.
  • Concurrent use of other anti-cancer therapies.
  • Pregnant or breast feeding females. (Lactating females may be considered if they agree not to breast feed while receiving study treatment and until 12 months following last dose of rituximab).
  • History of pulmonary embolus or deep vein thrombosis.
  • Clinically significant heart dysfunction, defined as New York Heart Association class III or IV, at the time of screening, or history of myocardial infarction or heart failure within 6 months preceding the first study treatment (cardiac ejection fraction must be >= 50% within 8 weeks of beginning study treatment for any patient with a history of clinically significant heart dysfunction).
  • Known positive for HIV, hepatitis B surface Ag, hepatitis B core antibody, or hepatitis C. Mandatory testing is not required, but should be considered in patients deemed high risk or suspicious.
  • Active infection requiring oral or intravenous antibiotics at study entry. After infection resolves patient may be evaluated for enrollment.
  • Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura.
  • Richter's transformation.
  • CNS involvement.
  • Other severe, acute, or chronic medical or psychiatric condition, laboratory abnormality, or difficulty complying with protocol requirements that may increase the risk associated with study participation or study drug administration or may interfere with interpretation of study results that in the judgment of the investigator would make the patient inappropriate for this study or that would prevent the patient from signing the informed consent form.
  • Use of any other biologic agent or disease-modifying anti-rheumatic drugs (DMARDS).
  • Known anaphylaxis or IgE-mediated hypersensitivity to murine proteins or any component of rituximab.
  • Evidence of laboratory TLS by Cairo-Bishop criteria (subjects may be enrolled upon correction of electrolyte abnormalities).
  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: NCT00536341

Locations
United States, Florida
Florida Cancer Specialists
Fort Myers, Florida, United States, 33901
Florida Hospital Cancer Institute
Orlando, Florida, United States, 32804
United States, Maryland
Center for Cancer and Blood Disorders
Bethesda, Maryland, United States, 20817
National Capital Clinical Research Consortium
Bethesda, Maryland, United States, 20817
United States, South Carolina
South Carolina Oncology Associates, PA
Columbia, South Carolina, United States, 29210
United States, Tennessee
Tennessee Oncology, PLLC
Nashville, Tennessee, United States, 37023
Sponsors and Collaborators
SCRI Development Innovations, LLC
Celgene Corporation
Genentech
Investigators
Study Chair: Ian W. Flinn, M.D. SCRI Development Innovations, LLC
  More Information

Additional Information:
No publications provided

Responsible Party: SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier: NCT00536341     History of Changes
Other Study ID Numbers: SCRI CLL 02
Study First Received: September 24, 2007
Last Updated: April 9, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by SCRI Development Innovations, LLC:
Chronic Lymphocytic Leukemia
untreated
minimally treated
fludarabine
rituximab
lenalidomide

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

ClinicalTrials.gov processed this record on September 18, 2014