Phase 1-2 of Azacitidine + Lenalidomide for Previously Untreated Elderly Patients With Acute Myeloid Leukemia (AML)

NCT00890929 | Completed Phase 1 Results DMC

• 4 other identifiers: IRB-15611SU-04242009-2385RV-AML-0410HEMAML0011
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

This study has a phase 1 and a phase 2 component. In phase 1, the objective is to determine the maximum tolerated dose (MTD) of lenalidomide when after azacitidine. In phase 2, the objective is to determine the efficacy of the combination treatment.

Conditions

Acute Myeloid Leukemia (AML); Adult Acute Myeloblastic Leukemia

Keywords

Acute myeloid leukemia; Acute myeloblastic leukemia; AML

Outcome Measures

Primary Outcomes (1)

• Compete Remission (CR) Rate

  Compete Remission (CR) includes subjects with CR but incomplete recovery of blood counts (CRi). CR was assessed according to the European LeukemiaNet (ELN) guidelines, and is defined as the absence of clonal lymphocytes in the peripheral blood.

  12 months

Secondary Outcomes (8)

• 4-week Survival Rate

  28 days

• Maximum Tolerated Dose (MTD) of Lenalidomide

  15 months

• Remission Duration

  26 months

• Overall Response Rate (ORR)

  26 months

• Overall Survival (OS)

  88 weeks (median)

Study Arms (1)

Azacitidine followed by lenalidomide

EXPERIMENTAL

Dose escalation then dose expansion

Drug: Lenalidomide; Drug: Azacitidine

Interventions

Lenalidomide DRUG

5 mg, 10 mg, 25 mg, and/or 50 mg of lenalidomide administered PO from day 8 to Day 28 of each cycle

Also known as: CC-5013, Revlimid

Azacitidine followed by lenalidomide

Azacitidine DRUG

75 mg/m2 Azacitidine administered intravenously (IV) or subcutaneously (SC) for days 1 to 7 of each cycle

Also known as: 5-azacytidine, Vidaza

Azacitidine followed by lenalidomide

Eligibility Criteria

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

You may qualify if:

• WHO-confirmed acute myeloid leukemia (AML), except acute promyelocytic leukemia (APL)
• White blood cell count (WBC) at initiation of treatment ≤ 10,000
• ◦If WBC is \> 10,000 patients may be started on an appropriate dose of hydroxyurea (to be determined by the investigators), until WBC \< 10,000, at which time the hydroxyurea will be discontinued for 24 hours prior to enrollment
• Age ≥ 60 years and not a candidate for allogeneic stem cell transplantation
• Unwilling or unable to receive conventional chemotherapy
• No prior therapy, except supportive care measures such as growth factor support, blood product transfusions, apheresis, or hydroxyurea
• ECOG performance status ≤ 2
• Life expectancy \> 2 months
• All study participants must be registered into the mandatory RevAssist® program, and must be willing and able to comply with the requirements of RevAssist
• If a female of childbearing potential (FCBP):
• Must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 to 14 days prior to study enrollment and again within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days)
• Must commit to either 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 starting lenalidomide.
• Must also agree to ongoing pregnancy testing.
• Male partners must use a latex condom during sexual contact, including if the male partners has previously had a successful vasectomy.
• Able to adhere to the study visit schedule and other protocol requirements

You may not qualify if:

• Relapsed or refractory disease
• Prior therapy with lenalidomide
• History of intolerance to thalidomide or development of erythema nodosum while taking thalidomide or similar drugs
• Known or suspected hypersensitivity to azacitidine or mannitol
• Advanced malignant hepatic tumors
• Concomitant treatment with other anti-neoplastic agents, except hydroxyurea
• Anti-neoplastic treatment less than four weeks prior to enrollment, except hydroxyurea
• Use of any other experimental drug or therapy within 28 days of baseline
• Inability to swallow or absorb drug
• Active opportunistic infection or treatment for opportunistic infection within four weeks of first day of study drug dosing
• New York Heart Association Class III or IV heart failure
• Unstable angina pectoris
• Uncontrolled cardiac arrhythmia
• Uncontrolled psychiatric illness that would limit compliance with requirements
• Known HIV infection

Sponsors & Collaborators

• Stanford University: lead
• Celgene Corporation: collaborator

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Related Publications (2)

• Pollyea DA, Zehnder J, Coutre S, Gotlib JR, Gallegos L, Abdel-Wahab O, Greenberg P, Zhang B, Liedtke M, Berube C, Levine R, Mitchell BS, Medeiros BC. Sequential azacitidine plus lenalidomide combination for elderly patients with untreated acute myeloid leukemia. Haematologica. 2013 Apr;98(4):591-6. doi: 10.3324/haematol.2012.076414. Epub 2012 Dec 14.

  PMID: 23242596 DERIVED

• Pollyea DA, Kohrt HE, Gallegos L, Figueroa ME, Abdel-Wahab O, Zhang B, Bhattacharya S, Zehnder J, Liedtke M, Gotlib JR, Coutre S, Berube C, Melnick A, Levine R, Mitchell BS, Medeiros BC. Safety, efficacy and biological predictors of response to sequential azacitidine and lenalidomide for elderly patients with acute myeloid leukemia. Leukemia. 2012 May;26(5):893-901. doi: 10.1038/leu.2011.294. Epub 2011 Oct 28.

  PMID: 22033493 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Lenalidomide; Azacitidine

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; Aza Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Bruno C Medeiros, MD
• Organization: Stanford University Medical Center

bruno.medeiros@stanford.edu

650-498-6000

Study Officials

• Bruno Carneiro de Medeiros

  Stanford University

  PRINCIPAL INVESTIGATOR

• Daniel Aaron Pollyea

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: April 28, 2009
• First Posted: April 30, 2009
• Study Start: April 1, 2009
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2012
• Last Updated: June 18, 2018
• Results First Posted: October 20, 2014

Record last verified: 2018-05

Locations

US (1)