Lenalidomide in Older Patients With Acute Myeloid Leukemia Without Chromosome 5q Abnormalities

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00546897
First received: October 17, 2007
Last updated: August 9, 2013
Last verified: August 2013
  Purpose

This study is designed to test the safety and efficacy of lenalidomide in older patients (age > 60 years) with untreated acute myeloid leukemia without chromosomal abnormalities involving 5q.


Condition Intervention Phase
Leukemia, Myeloid, Acute
Drug: Lenalidomide
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: Phase II Trial of Lenalidomide in Older Patients (>/= 60 Years) With Untreated Acute Myeloid Leukemia Without Chromosome 5q Abnormalities

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • To assess the morphologic complete remission rate (CR) of lenalidomide therapy in this patient population [ Time Frame: 30 days, 60 days, and after 2 cycles of low dose therapy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To assess the safety and tolerability of lenalidomide therapy in this patient population [ Time Frame: 4 weeks after last dose of study drug ] [ Designated as safety issue: Yes ]
  • To assess the response rate (RR), morphologic leukemia-free state, morphologic complete remission rate (CRm), cytogenetics CR (CRc) rate, CR with incomplete blood counts (CRi) rate, and partial remission (PR) rate [ Time Frame: 30 days, 60 days, and after 2 cycles of low dose therapy ] [ Designated as safety issue: No ]
  • To assess time to progression (TTP) [ Time Frame: 30 days, 60 days, and after 2 cycles of low dose therapy ] [ Designated as safety issue: No ]
  • To assess overall survival (OS) and event free survival (EFS) [ Time Frame: Minimum of 1 year ] [ Designated as safety issue: No ]
  • To assess relapse free survival (RFS) and duration of CR for complete responders [ Time Frame: Minimum of 1 year ] [ Designated as safety issue: No ]
  • To evaluate changes in NK cell number and function, gene expression profiles of bone marrow and peripheral blood, and plasma proteins via proteomics, before, during, and after lenalidomide therapy (correlative studies) [ Time Frame: C1D15, Day 30, Day 60, Cycle 2, 4, 6, and 12 of low dose lenalidomide, and off study ] [ Designated as safety issue: No ]

Enrollment: 48
Study Start Date: February 2007
Study Completion Date: March 2012
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1

Lenalidomide 50 mg/day oral for 28 days - Cycle 1 and Cycle 2 if no progressive disease

Lenalidomide 10 mg/day oral for 28 days for 12 cycles

Drug: Lenalidomide
Other Names:
  • Revlimid
  • CC-5013

Detailed Description:

The incidence of AML increases with age, and current treatment options for the older patient population with newly diagnosed AML (AML >= 60) is limited, all with poor outcomes. AML >= 60 patients are more likely to have poor-risk cytogenetics abnormalities, and many have a preceding myelodysplastic syndrome (MDS). Traditional induction chemotherapy approaches in AML with cytarabine and anthracyclines yield remissions in 45-60% of AML >= 60, however the vast majority of these patients relapse with a median survival of about 9 months. These patients are rarely candidates for potentially curative allogeneic stem cell transplantation. Many untreated AML >= 60 patients are not candidates for aggressive therapy, and those who do receive therapy have a significant induction mortality of 10-20%, and significant hematologic toxicity occurs in over 30%, with no change in overall survival compared with supportive care. AML >= 60 patients with favorable risk cytogenetics have a modest improvement in prognosis, for example with a 5 year overall survival of ~20%, compared with 0% in other cytogenetic categories. Thus, all eligible patients with AML >= 60 should be recommended a clinical trial, regardless of whether they would be offered generally ineffective traditional induction chemotherapy. More effective and less toxic therapies are needed for the treatment of AML in this older patient population, indeed the preferred first line therapy in the national cancer center network (NCCN) guidelines for AML is a clinical trial.

In trials of lenalidomide in patients with MDS the dose of lenalidomide has been reduced for myelotoxicity and/or thrombocytopenia. However, current paradigms for the therapy of acute myeloid leukemia are based on using high doses of myelosuppressive chemotherapy and supporting the patient through a 4-5 weeks period of neutropenia/thrombocytopenia in an attempt to eliminate the malignant clone. Based on its efficacy in the related myeloid disorder MDS, and the close relationship between MDS and AML in patients > 60, this trial employs the same paradigm of myelosuppressive therapy using high dose lenalidomide instead of chemotherapy. Importantly, within the MDS trials using low doses of lenalidomide, responses were observed in 3/9 (33%) of patients with excess blasts (RAEB/RAEB-t), which are now classified as evolving into AML or AML. This suggests that the therapeutic effect of lenalidomide occurs in the setting of a large percentage of blasts, such as AML, although the dose and schedule of lenalidomide administration is different. The response of AML >= 60 patients to the proposed high dose lenalidomide regimen is unknown. Following high dose lenalidomide, in those patients that have a response, we propose using a lower dose maintenance strategy similar to the FDA approved dosing for MDS. The maintenance phase will include standard dose reductions for unacceptable toxicities.

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • AML, de novo, secondary to prior therapy, or transformed from MDS, as defined by the International Working Group (except acute promyelocytic leukemia (AML M3). Patients must not have abnormalities of chromosome 5q as assessed by routine cytogenetics or FISH. Diagnosis of AML by WHO criteria (≥20% blasts) is determined by CBC, bone marrow assessment, and immunophenotypic analysis performed within 2 weeks of study enrollment.
  • Intermediate or poor-risk cytogenetics as defined by SWOG criteria
  • Age ≥ 60 years at the time of signing the informed consent form.
  • Understand and voluntarily sign an informed consent form.
  • Able to adhere to the study visit schedule and other protocol requirements.
  • No previous treatment for AML, however hydroxyurea, steroids, and leukopheresis are allowed
  • ECOG performance status of ≤ 2 at study entry.
  • Life expectancy > 2 months
  • Adequate organ function as defined by:
  • Serum creatinine ≤ 1.5X institution upper limit of normal (ULN)
  • Total bilirubin ≤ 2.0 mg/dL
  • AST (SGOT) and ALT (SGPT) ≤ 5 x ULN
  • 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 had 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 ≥ 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast.

Exclusion Criteria:

  • Received prior treatment for AML
  • Favorable risk cytogenetic abnormalities as defined by SWOG criteria (http://www.bloodjournal.org/cgi/content/abstract/96/13/4075) that include: inv(16)/t(16;16)/del(16q), t(15;17) with/without secondary aberrations, t(8;21) lacking del(9q) or complex karyotype (16). Prior to enrollment, FISH, molecular studies or routine cytogenetics must be completed to rule out these cytogenetic abnormalities.
  • Known CNS leukemia
  • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
  • Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
  • Use of any other experimental drug or therapy within 30 days of enrollment.
  • Known hypersensitivity to thalidomide.
  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: NCT00546897

Locations
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Ravi Vij, M.D. Washington University School of Medicine
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00546897     History of Changes
Other Study ID Numbers: 06-0907
Study First Received: October 17, 2007
Last Updated: August 9, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Congenital Abnormalities
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Lenalidomide
Thalidomide
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on August 28, 2014