Lenalidomide in Older Patients With Acute Myeloid Leukemia Without Chromosome 5q Abnormalities - Full Text View

Sponsored by:	Washington University School of Medicine
Information provided by:	Washington University School of Medicine
ClinicalTrials.gov Identifier:	NCT00546897

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 II

MedlinePlus related topics: Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Lenalidomide CC 5013

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title:	Phase II Trial of Lenalidomide in Older Patients (> 60 Years) With Untreated Acute Myeloid Leukemia Without Chromosome 5q Abnormalities

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: At 30 and 60 days post therapy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To assess the safety and tolerability of lenalidomide therapy in this patient population [ Time Frame: Continuous throughout study ] [ 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: At 30 and 60 days post therapy ] [ Designated as safety issue: No ]
To assess time to progression (TTP) [ Time Frame: Continuous throughout study ] [ Designated as safety issue: No ]
To assess overall survival (OS) and event free survival (EFS) [ Time Frame: Continuous throughout study ] [ Designated as safety issue: No ]
To assess relapse free survival (RFS) and duration of CR for complete responders [ Time Frame: Continuous throughout study ] [ 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: At 30 and 60 days post therapy ] [ Designated as safety issue: No ]

Estimated Enrollment:	42
Study Start Date:	February 2007
Estimated Study Completion Date:	September 2014
Estimated Primary Completion Date:	September 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Lenalidomide	Drug: Lenalidomide High dose lenalidomide 50 mg po will be administered daily in a 28 day cycle for up to 2 cycles. Patients without evidence of disease progression will continue on low dose lenalidomide 10 mg po daily in a 28 day cycle for up to 12 cycles.

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00546897

Contacts

Contact: Ravi Vij, M.D.

314-454-8304

rvij@dom.wustl.edu

Locations

United States, Missouri
Washington University School of Medicine	Recruiting
St. Louis, Missouri, United States, 63110
Sub-Investigator: Todd A. Fehniger, M.D., Ph.D.
Sub-Investigator: Camille N. Abboud, M.D.
Sub-Investigator: Amanda F. Cashen, M.D.
Sub-Investigator: John F. DiPersio, M.D., Ph.D.
Sub-Investigator: Timothy A. Graubert, M.D.
Sub-Investigator: Timothy J. Ley, M.D.
Sub-Investigator: Keith E. Stockerl-Goldstein, M.D.
Sub-Investigator: Michael H. Tomasson, M.D.
Sub-Investigator: Geoffrey Uy, M.D.
Sub-Investigator: Matthew Walter, M.D.
Sub-Investigator: Peter Westervelt, M.D., Ph.D.

Sponsors and Collaborators

Washington University School of Medicine

Investigators

Principal Investigator:

Ravi Vij, M.D.

Washington University in St. Louis

More Information

Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine This link exits the ClinicalTrials.gov site

This link exits the ClinicalTrials.gov site

Publications:

List A, Kurtin S, Roe DJ, Buresh A, Mahadevan D, Fuchs D, Rimsza L, Heaton R, Knight R, Zeldis JB. Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med. 2005 Feb 10;352(6):549-57.

Responsible Party:	Washington University ( Ravi Vij, M.D., Principal Investigator )
Study ID Numbers:	06-0907
Study First Received:	October 17, 2007
Last Updated:	November 7, 2008
ClinicalTrials.gov Identifier:	NCT00546897
Health Authority:	United States: Food and Drug Administration

Study placed in the following topic categories:

Leukemia
Lenalidomide
Acute myelogenous leukemia
Leukemia, Myeloid

Congenital Abnormalities
Leukemia, Myeloid, Acute
Acute myelocytic leukemia

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Histologic Type
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009