5-Azacytidine With Lenalidomide in Patients With High Risk Myelodysplastic Syndrome (MDS) and Acute Myelogenous Leukemia (AML)

NCT01038635 | Completed Phase 1 Results

• 2 other identifiers: 2009-0467NCI-2011-01941
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of Phase 1 of this clinical research study is to find the highest tolerable dose of lenalidomide that can be given in combination with azacitidine to patients with MDS or AML. The goal of Phase 2 of this study is to learn if the combination dose of azacitidine and lenalidomide found in Phase 1 can help to control MDS and/or AML. The safety of this drug combination will be studied in both Phases.

Conditions

Leukemia

Keywords

5-Azacytidine; 5-Aza; Lenalidomide; Revlimid; CC-5103; Myelodysplastic Syndrome; MDS; Acute Myelogenous Leukemia; AML

Outcome Measures

Primary Outcomes (1)

• Number of Dose Limiting Toxicities for Determining Maximum Tolerated Dose (MTD) of Lenalidomide in Combination With 5-azacytidine (5-AZA)

  DLT determined only during first course of therapy, at least 28 days from treatment of last participant before a new dose level initiated. All severe (Grade 3-4) non-hematological toxicities that are drug related considered for DLT determination. If 1 participant develops grade III-IV non-hematological toxicity, 3 more will be accrued at that particular dose level. If 2 or more participants develop grade III-IV non-hematologic toxicity, the doses of the combination at which this occurs will be considered too toxic. A total of 10 patients will be treated at the maximally tolerated dose (MTD) of the combination (the dose level below that considered to be too toxic) to confirm its tolerability.

  3-8 week cycles, up to 24 weeks

Secondary Outcomes (2)

• Overall Response Rate (ORR) of Lenalidomide in Combination With 5-azacytidine (5-AZA) in Participants With Leukemia

  6 months

• Overall Response: Number of Participants With CR or CRi Response

  6 months

Study Arms (1)

5-Azacytidine + Lenalidomide

EXPERIMENTAL

5-Azacytidine 75 mg/m\^2 by vein daily x 5 days on days 1 to 5. Lenalidomide starting dose 10 mg orally daily x 5 days on days 6 to 10.

Drug: 5-Azacytidine; Drug: Lenalidomide

Interventions

5-Azacytidine DRUG

75 mg/m\^2 IV daily x 5 days on days 1 to 5.

Also known as: 5-AZA, Azacitidine, Vidaza, 5-AZC, AZA-CR, Ladakamycin

5-Azacytidine + Lenalidomide

Lenalidomide DRUG

Starting dose 10 mg orally daily x 5 days on days 6 to 10.

Also known as: CC-5013, Revlimid

5-Azacytidine + Lenalidomide

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with higher risk MDS (bone marrow blasts \>/= 10% to 30% inclusive) of any age who refuse or are not eligible for frontline chemotherapy.
• No prior therapy for higher risk MDS as defined above.
• Performance status of \</= 2 by the Eastern Cooperative Oncology Group (ECOG) scale.
• Signed informed consent indicating that patients are aware of the investigational nature of this study in keeping with the policies of University of Texas MD Anderson Cancer Center (UTMDACC).
• Hydroxyurea for patients with rapidly proliferative disease can be used up to 24 hours prior to therapy but not concomitantly with 5-azacitidine or lenalidomide. Hydroxyurea can be used once the patient has completed the planned 5 azacitidine and lenalidomide treatment.
• Adequate liver function: Total bilirubin of \</= 1.5 x upper limit of normal (ULN), AST (SGOT) and ALT (SGPT) \</= 3 x ULN
• Renal function - assessed by calculated creatinine clearance as follows (see Appendix: Cockcroft-Gault estimation of CrCl): 1. Phase I subjects must have calculated creatinine clearance \>/= 60ml/min by Cockcroft-Gault formula. 2. Phase II subjects must have calculated creatinine clearance \>/= 30ml/min by Cockcroft-Gault formula.
• All study participants must be registered into the mandatory Revlimid REMS® program, and be willing and able to comply with the requirements of Revlimid REMS®.
• Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program.
• Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin).
• 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 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.
• Continued from #9: Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy.

You may not qualify if:

• Nursing and pregnant females.
• Known or suspected hypersensitivity to azacitidine or mannitol.
• Patients with advanced malignant hepatic tumors.
• Unwilling or unable to remain in compliance with the RevAssist® program
• Known hypersensitivity to thalidomide or lenalidomide (if applicable).
• The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
• Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine are eligible.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Celgene: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• DiNardo CD, Daver N, Jabbour E, Kadia T, Borthakur G, Konopleva M, Pemmaraju N, Yang H, Pierce S, Wierda W, Bueso-Ramos C, Patel KP, Cortes JE, Ravandi F, Kantarjian HM, Garcia-Manero G. Sequential azacitidine and lenalidomide in patients with high-risk myelodysplastic syndromes and acute myeloid leukaemia: a single-arm, phase 1/2 study. Lancet Haematol. 2015 Jan;2(1):e12-20. doi: 10.1016/S2352-3026(14)00026-X. Epub 2014 Dec 22.

  PMID: 26687423 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes; Leukemia, Myeloid, Acute

Interventions

Azacitidine; Lenalidomide

Condition Hierarchy (Ancestors)

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

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: Guillermo Garcia-Manero, MD/Professor, Leukemia
• Organization: The University of Texas (UT) MD Anderson Cancer Center

CR_Study_Registration@mdanderson.org

713-792-7734

Study Officials

• Guillermo Garcia-Manero, MD

  M.D. Anderson Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2009
• First Posted: December 24, 2009
• Study Start: December 1, 2009
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: February 10, 2017
• Results First Posted: February 10, 2017

Record last verified: 2016-12

Locations

US (1)