Combination of 5-azacitidine and Lenalidomide in Myelodysplastic Syndromes (MDS) or Acute Myelogenous Leukemia (AML) Myelodysplastic Syndromes

NCT00923234 | Terminated Phase 1 DMC

• 1 other identifier: TUD-AZALE1-037
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 4

Brief Summary

The hypothesis of this study is that 5-aza and lenalidomide act synergistically in MDS and AML patients with chromosomal abnormalities involving monosomy 5 or del5q. Therefore, this phase I study will investigate the maximum tolerated dose (MTD) of lenalidomide in combination with a fixed dose of 5-aza in this patient population.

Conditions

Myelodysplastic Syndromes; Acute Myelogenous Leukemia

Keywords

monosomy 5; del5q; lenalidomide; azacitidine

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD) of Revlimid® (lenalidomide)in combination with Vidaza®(5-azacitidine)

  during first cycle of therapy

Secondary Outcomes (2)

• Clinical and cytogenetic response

  during therapy

• Safety (type, frequency, severity, and relationship of adverse events to study treatment)

  during therapy

Study Arms (1)

Azacitidine and Lenalidomide

EXPERIMENTAL

Azacitidine 75 mg/m² SC days 1-5 every 28 days for a maximum of 8 cycles and Lenalidomide 10 - 25 mg PO days 6-19 every 28 days for a maximum of 8 cycles

Drug: Azacitidine; Drug: Lenalidomide

Interventions

Azacitidine DRUG

75 mg/m² SC days 1-5 every 28 days for a maximum of 8 cycles

Also known as: Vidaza

Azacitidine and Lenalidomide

Lenalidomide DRUG

10 - 25 mg PO days 6-19 every 28 days for a maximum of 8 cycles

Also known as: Revlimid

Azacitidine and Lenalidomide

Eligibility Criteria

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

You may qualify if:

• Understand and voluntarily sign an informed consent form.
• Age \>=18 years at the time of signing the informed consent form.
• Able to adhere to the study visit schedule and other protocol requirements.
• Relapsed or refractory AML (\>30% blasts, FAB classification)with karyotype abnormalities involving monosomy 5 or del(5q) or MDS and t-MDS INT-2 or HIGH according to IPSS classification with karyotype abnormalities involving monosomy 5 or del(5q) either previously treated or untreated
• Not eligible for an immediate allogeneic HSCT (due to donor unavailability)
• All previous MDS or AML specific therapy with exception of corticosteroids not exceeding doses of 10mg/day prednisone must have been discontinued at least 1 week prior to study enrollment.
• Non-hematological toxicity (except alopecia) resulting from previous treatment must be resolved to WHO CTC Grade ≤ 2.
• ECOG performance status of \< 3 at study entry.
• Laboratory test results within these ranges:Serum creatinine \<= 2.0 mg/dL, Total bilirubin \<= 3 x ULN, AST (SGOT) and ALT (SGPT) \<= 3 x ULN
• Females of childbearing potential must agree to use a reliable form of contraception or to practice complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) for at least 28 days before starting study drug; 2) while participating in the study; and 3) for at least 28 days after discontinuation from the study.

You may not qualify if:

• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
• Pregnant or breast feeding females. (Lactating females must agree not to breast feed while on study).
• 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.
• Known hypersensitivity to thalidomide, lenalidomide, 5-azacitidine or mannitol.
• Myocardial infarction within 6 months before study entry, New York Heart Association Class III or IV heart failure, uncontrolled angina or severe uncontrolled ventricular arrhythmias.
• The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
• Uncontrolled lung disease.
• Known positive for HIV or acute infectious hepatitis, type A, B or C.
• Participation in another clinical study in the 4 weeks prior to enrollment or during this study.

Sponsors & Collaborators

• Technische Universität Dresden: lead
• Celgene Corporation: collaborator

Study Sites (4)

Medizinische Klinik und Poliklinik I, Uniklinik

Dresden, Germany

Location

Universitätsklinikum Düsseldorf, Klinik für Hämatologie/Onkologie/klinische Immunologie

Düsseldorf, 40225, Germany

Location

Klinikum der J.W. Goethe-Universität, Medizinische Klink II

Frankfurt, 60590, Germany

Location

Technische Universität München, Klinikum Rechts der Isar

München, 81675, Germany

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myeloid, Acute

Interventions

Azacitidine; Lenalidomide

Condition Hierarchy (Ancestors)

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

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

Study Officials

• Uwe Platzbecker, MD

  Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus

  PRINCIPAL INVESTIGATOR

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: June 17, 2009
• First Posted: June 18, 2009
• Study Start: June 1, 2009
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: December 18, 2013

Record last verified: 2013-12

Locations

DE (4)