Azacitidine and Lenalidomide for Relapsed and Refractory Patients With Acute Myeloid Leukemia

NCT01743859 | Completed Phase 2 Results DMC

• 2 other identifiers: 12-1283.ccNCI-2012-03191
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to determine the complete remission/complete remission with incomplete recovery of blood counts (CR/CRi) rate for relapsed and refractory acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) patients.

Conditions

Acute Myeloid Leukemia

Keywords

Myeloid; Leukemia

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Complete Remission or Complete Remission With Incomplete Recovery Blood Counts

  Change in baseline to end of study. To be assessed by standard criteria based on bone marrow examination. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

  Interim assessment after 18 patients (estimated 2 years) and full assessment after 37 patients (estimated 3-4 years)

• Overall Response Rate

  Change in baseline to end of study. To be assessed by standard criteria based on bone marrow examination

  Planned assessment after enrollment of all 37 patients (estimated 3-4 years)

Secondary Outcomes (5)

• Response or Remission Duration

  Depending on outcomes, will initiate this assessment after 2 years and will continue until completion of study, estimated at 4 years

• Toxicity and SAEs Related to Treatment

  Will begin assessment with first patient and will continue until completion of study, estimated to be 4 years

• Overall Survival

  Depending on outcomes, will begin assessment at 2 years and will continue until completion of study, estimated to be at four years

• Progression-free Survival

  Depending on outcomes, will initiate this assessment after 2 years and will continue until completion of study, estimated at 4 years

• Determine Biomarkers That Predict Response/Toxicity

  Three years after initiating study

Study Arms (1)

Azacitidine + Lenalidomide + Off Therapy

EXPERIMENTAL

Patients will receive 7 days of azacitidine followed by 3 weeks of lenalidomide. They will then have 2 weeks off therapy, for a maximum of 12 cycles.

Drug: Azacitidine; Drug: Lenalidomide; Other: Off Therapy

Interventions

Azacitidine DRUG

Enrolled patients will receive 75 mg/m2 of azacitidine subcutaneously (SC) or intravenously (IV) on days 1-7 alone.

Also known as: Vidaza (TM)

Azacitidine + Lenalidomide + Off Therapy

Lenalidomide DRUG

Beginning on day 8, patients will receive 50 mg of lenalidomide PO, and will take this daily from day 8 through 28.

Also known as: Revlimid (TM)

Azacitidine + Lenalidomide + Off Therapy

Off Therapy OTHER

2 weeks off therapy, then begin sequence again for 12 weeks.

Azacitidine + Lenalidomide + Off Therapy

Eligibility Criteria

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

You may qualify if:

• World Health Organization (WHO)-confirmed AML, other than Acute Promyelocytic Leukemia (APL)
• Age \>18 years
• White blood cell count (WBC) at initiation of treatment ≤ 10,000/L
• o If WBC is \> 10,000/L patients may be started on an appropriate dose of hydroxyurea (to be determined by the investigators), until WBC \< 10,000/L, at which time the hydroxyurea will be discontinued for 12 hours prior to enrollment
• Relapsed or refractory (resistant) disease, as defined by standard criteria21:
• Relapsed: Bone marrow blasts ≥5%; reappearance of blasts in the blood; development of extramedullary disease
• Refractory (resistant): Failure to achieve Complete Remission (CR) or complete remission with incomplete recovery of blood counts (CRi) in patients who survive ≥7 days following completion of initial treatment, with evidence of persistent leukemia by blood and/or bone marrow examination
• Failure of at least one prior therapy
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (See Appendix D: ECOG Performance Status Scale)
• Life expectancy \> 2 months
• All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist® (RevAssist is a restricted distribution program for receiving lenalidomide)
• Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 million International Units per milliliter (mIU/mL) 10 - 14 days prior to study enrollment and again within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days) 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. See Appendix F: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods
• Willing and able to understand and voluntarily sign a written informed consent
• Able to adhere to the study visit schedule and other protocol requirements

You may not qualify if:

• Known or suspected hypersensitivity to azacitidine or mannitol
• Patients with advanced malignant hepatic tumors.
• Treatment less than four weeks prior to enrollment with other experimental therapies or antineoplastic agents, with the exception of hydroxyurea
• Inability to swallow or absorb drug
• Prior treatment with lenalidomide for AML
• 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
• Significant uncontrolled cardiac arrhythmias
• Uncontrolled psychiatric illness that would limit compliance with requirements
• Known Human immunodeficiency virus (HIV) infection
• Graft vs. host disease ≥ grade 2
• Relapse after allogeneic stem cell transplantation prior to post-transplant day 30
• Pregnant or breast feeding females; lactating females must agree not to breast feed while taking lenalidomide
• Other medical or psychiatric illness or organ dysfunction or laboratory abnormality which in the opinion of the investigator would compromise the patient's safety or interfere with data interpretation

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Celgene: collaborator

Study Sites (1)

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia

Interventions

Azacitidine; Lenalidomide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Dr. Daniel Pollyea
• Organization: University of Colorado

daniel.pollyea@ucdenver.edu

Study Officials

• Daniel Pollyea, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2012
• First Posted: December 6, 2012
• Study Start: December 6, 2012
• Primary Completion: April 27, 2016
• Study Completion: August 3, 2016
• Last Updated: October 8, 2019
• Results First Posted: October 8, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)