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

NCT00546897 | Completed Phase 2 Results DMC

• 1 other identifier: 06-0907
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Leukemia, Myeloid, Acute

Outcome Measures

Primary Outcomes (1)

• Complete Remission Rate (CRm + CRi + CRc)

  CRm = Defined as morphologic leukemia-free state, including \<5% blasts in BM aspirate with marrow spicules and a count of \> 200 nucleated cells and no blasts with Auer rods, no persistent extramedullary disease, ANC \> 1000/uL, platelet count \>100,000/uL. Patient must be independent of transfusions for a minimum of 1 week before each marrow assessment. There is no duration requirement for this designation. CRi = Defined as CR with the exception of neutropenia \<1000/uL or thrombocytopenia \<100,000/ul. Cytogenetic complete remission (CRc): Only patients with an identified cytogenetic abnormality may receive this designation. Defines as a morphologic complete remission plus reversion to a normal karyotype (no clonal abnormalities detected in a minimum of 20 mitotic cells).

  After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2)

Secondary Outcomes (15)

• Safety and Tolerability (Removal From Study Due to Adverse Events)

  4 weeks after last dose of study drug [median duration of therapy was 65 days (range, 3-413 days)]

• Response Rate (RR)

  After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2)

• Morphologic Leukemia Free State

  After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2)

• Morphologic Complete Remission Rate (CRm)

  After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2)

• Cytogenetics CR Rate (CRc)

  After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2)

Study Arms (2)

Cohort 1

EXPERIMENTAL

Lenalidomide 50 mg/day oral for 14 days followed by 30 days of rest. Lenalidomide 50 mg/day oral for 21 days (this is Cycle 1 and Cycle 2). If no progressive disease (PD) then lenalidomide 10 mg/day oral for 28 days for 12 cycles.

Drug: Lenalidomide

Cohort 2

EXPERIMENTAL

Cycle 1: Oral lenalidomide 50 mg/day x 28 days induction therapy. Treatment will then depend on the response to Cycle 1: if patients obtain a complete remission (CR) they will proceed to low dose lenalidomide therapy, if patients have a non-CR they will receive a second high dose cycle of lenalidomide 50 mg/day x 28 days (Cycle 2) Cycle 2 consists of lenalidomide 50mg/day x 28 days Further treatment will depend on the response to Cycle 2: if patients obtain a CR/partial remission (PR)/stable disease (SD) they will proceed to low dose lenalidomide therapy, if patients have PD they will be removed from the study. Low Dose Cycles: low dose lenalidomide therapy consisting of 10 mg daily for a 28 day cycle.be 1) For patients that achieve a CR, 2 cycles of low dose lenalidomide will be administered, and then patients observed off therapy. For patients with PR/SD, low dose lenalidomide will continue for a total of 6 cycles and then patients will be observed off therapy.

Drug: Lenalidomide

Interventions

Lenalidomide DRUG

Also known as: Revlimid, CC-5013

Cohort 1; Cohort 2

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (5)

• 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. doi: 10.1056/NEJMoa041668.

  PMID: 15703420 BACKGROUND

• List, AF, G Dewald, J Bennett, et al. 2005. Hematologic and Cytogenetic (CTG) Response to Lenalidomide (CC-5013) in Patients with Transfusion-Dependent (TD) Myelodysplastic Syndrome (MDS) and Chromosome 5q31.1 Deletion: Results of the Multicenter MDS-003 Study. In ASCO, Orlando, FL.

  BACKGROUND

• Bansal D, Vij K, Chang GS, Miller CA, DiPersio JF, Vij R, Heath SE, Westervelt P, Welch JS, Fehniger TA. Lenalidomide results in a durable complete remission in acute myeloid leukemia accompanied by persistence of somatic mutations and a T-cell infiltrate in the bone marrow. Haematologica. 2018 Jun;103(6):e270-e273. doi: 10.3324/haematol.2017.184168. Epub 2018 Mar 22. No abstract available.

  PMID: 29567774 DERIVED

• Fehniger TA, Uy GL, Trinkaus K, Nelson AD, Demland J, Abboud CN, Cashen AF, Stockerl-Goldstein KE, Westervelt P, DiPersio JF, Vij R. A phase 2 study of high-dose lenalidomide as initial therapy for older patients with acute myeloid leukemia. Blood. 2011 Feb 10;117(6):1828-33. doi: 10.1182/blood-2010-07-297143. Epub 2010 Nov 4.

  PMID: 21051557 DERIVED

• Fehniger TA, Byrd JC, Marcucci G, Abboud CN, Kefauver C, Payton JE, Vij R, Blum W. Single-agent lenalidomide induces complete remission of acute myeloid leukemia in patients with isolated trisomy 13. Blood. 2009 Jan 29;113(5):1002-5. doi: 10.1182/blood-2008-04-152678. Epub 2008 Sep 29.

  PMID: 18824593 DERIVED

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Lenalidomide

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

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

Results Point of Contact

• Title: Ravi Vij, M.D.
• Organization: Washington University School of Medicine

rvij@dom.wustl.edu

314-454-8304

Study Officials

• Ravi Vij, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 17, 2007
• First Posted: October 19, 2007
• Study Start: February 1, 2007
• Primary Completion: June 1, 2010
• Study Completion: March 1, 2012
• Last Updated: September 29, 2014
• Results First Posted: September 29, 2014

Record last verified: 2014-09

Locations

US (1)