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Lenalidomide in Acute Leukemias and Chronic Lymphocytic Leukemia.

Phase 1
Completed
Conditions
Chronic Lymphocytic Leukemia
Acute Myeloid Leukemia
Acute Lymphoblastic Leukemia
Interventions
Registration Number
NCT00466895
Lead Sponsor
Leslie Andritsos
Brief Summary

Phase I Study of Lenalidomide in Acute Leukemias and Chronic Lymphocytic Leukemia.

Detailed Description

Rationale:

Lenalidomide has properties of thalidomide and appears to have some activity against cancer in laboratory tests. Researchers are still learning how lenalidomide works against cancer in patients. Some ways that this drug seems to produce anti-cancer effects include through stimulating the immune system and blocking blood vessels contributing to cancer growth. The current study will explore different dose levels in patients to gather more information about lenalidomide.

Purpose:

This study will assess the maximum tolerated dose of lenalidomide in patients with relapsed or refractory acute leukemias and chronic lymphocytic leukemias. Toxicity or side effects within patients will also be evaluated. Other purposes of this study include analyzing preliminary clinical activity, pharmacokinetics, and pharmacodynamics. Pharmacokinetics refers to the activity of drugs in the body over a period of time, including how drugs are absorbed, distributed, localized in tissues, and excreted. Pharmacodynamics refers to the bodily processes that lead the drug to effect cancer and other cellular components in the body.

Treatment:

Study participants will be given lenalidomide through intravenous infusions once every 28 days. A 28-day period constitutes a cycle. Since this study will assess the maximum tolerated dose of lenalidomide, some study participants will receive different amounts of this drug compared to others depending upon when each individual enrolls in the study. Each group of 3 to 6 study participants will receive a higher dose of lenalidomide until the maximum tolerated dose is established. Several tests will be performed throughout the study, including bone marrow biopsies. Imaging exams will be conducted as well. Treatments will be discontinued due to disease growth or intolerable adverse effects. Lenalidomide administration will be repeated for 12 or more cycles in patients that experience clinical benefit.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
37
Inclusion Criteria
  • Blood blast count must be < 40,000/uL prior to initiation of therapy. Hydroxyurea (up to 6g/day) may be administered prior to initiation of therapy and during the first week to maintain blood blast count < 40,000/uL
  • ECOG(Eastern Cooperative Oncology Group)performance status 0-2.
  • Patients with CNS(central nervous system)involvement will be considered eligible for this study if no residual leukemic cells are detected in the CSF (cerebrospinal fluid)following intrathecal chemotherapy or radiation.
Exclusion Criteria
  • Patients with acute promyelocytic leukemia are excluded unless patient has failed salvage therapy with arsenic.
  • Patients with HIV are excluded due to increased risk of infectious complications, marrow suppression, and potential interactions with antiviral therapy.
  • CLL patients who have had chemotherapy (with the exception of hydroxyurea) or radiotherapy within 4 weeks prior to entering the study are excluded. CLL patients receiving corticosteroids (within 2 weeks) for treatment of disease (other than autoimmune manifestations of CLL) are not eligible.
  • Patients who have received mitomycin C or nitrosourea require a six weeks recovery period before they can be enrolled on the current study.
  • Patients with the following abnormal clinical values are excluded (unless abnormalities in these parameters are directly attributable to malignancy): Serum creatinine >2.0 mg/dl Total bilirubin > 2 x upper limit of normal (unless due to Gilbert's syndrome) ALT and AST > 5 x upper limit of normal

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Stratum 1 Acute LeukemiaslenalidomidePatients must have a diagnosis of Acute Myeloid Leukemia (AML) or Acute Lymphoblastic Leukemia(ALL)according to the WHO (World Health Organization) classification.
Stratum 2 Chronic lymphocytic leukemialenalidomidePatients must have diagnosis of B-Cell, Chronic Lymphocytic Leukemia(CLL) or Small Lymphocytic Leukemia (SLL) (including Waldenstrom's Macroglobulinemia) requiring therapy (see eligibility criteria for definition of this) and have previously received treatment with one or more prior chemotherapy regimens.
Primary Outcome Measures
NameTimeMethod
Toxicities of lenalidomideEvery 2 weeks during cycle 1; Monthly for subsequent cycles
Maximum tolerable doseEvery 2 weeks during cycle 1; Monthly during subsequent cycles
Secondary Outcome Measures
NameTimeMethod
pharmacodynamicsDays 1, 8 and 26.
preliminary clinical activityTwice weekly during cycle 1; Weekly during cycles 2-6; Monthly thereafter
plasma and cellular pharmacokineticsDays 1, 8, 15 and 21 of first cycle.

Trial Locations

Locations (1)

Ohio State University Medical Center

🇺🇸

Columbus, Ohio, United States

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