search
Back to results

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

Primary Purpose

Myelodysplastic Syndromes, Acute Myelogenous Leukemia

Status
Terminated
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Azacitidine
Lenalidomide
Sponsored by
Technische Universität Dresden
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myelodysplastic Syndromes focused on measuring monosomy 5, del5q, lenalidomide, azacitidine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Sites / Locations

  • Medizinische Klinik und Poliklinik I, Uniklinik
  • Universitätsklinikum Düsseldorf, Klinik für Hämatologie/Onkologie/klinische Immunologie
  • Klinikum der J.W. Goethe-Universität, Medizinische Klink II
  • Technische Universität München, Klinikum Rechts der Isar

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Azacitidine and Lenalidomide

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Clinical and cytogenetic response
Safety (type, frequency, severity, and relationship of adverse events to study treatment)

Full Information

First Posted
June 17, 2009
Last Updated
December 17, 2013
Sponsor
Technische Universität Dresden
Collaborators
Celgene Corporation
search

1. Study Identification

Unique Protocol Identification Number
NCT00923234
Brief Title
Combination of 5-azacitidine and Lenalidomide in Myelodysplastic Syndromes (MDS) or Acute Myelogenous Leukemia (AML) Myelodysplastic Syndromes
Acronym
AZALE
Official Title
A Phase I Study of a Combination of 5-azacitidine Followed by Lenalidomide in High-risk MDS or Relapsed/Refractory AML Patients With Cytogenetic Abnormalities Including -5 or Del(5q)
Study Type
Interventional

2. Study Status

Record Verification Date
December 2013
Overall Recruitment Status
Terminated
Why Stopped
The primary objective has already been answered with the number of recruited patients.
Study Start Date
June 2009 (undefined)
Primary Completion Date
July 2012 (Actual)
Study Completion Date
July 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Technische Universität Dresden
Collaborators
Celgene Corporation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
Cytogenetics are the main predictors of outcome in patients with AML. In fact, a monosomy 5 or del (5q) as single aberration are poor prognostic markers. Overall, the complete response rate for conventionally treated patients with newly-diagnosed AML with chromosome 5 abnormalities is about 31% to 37 % and all patients rapidly relapse if not rescued by allogeneic HSCT. The situation is almost similar in patients with high-risk MDS.Vidaza® has been shown in clinical trials to achieve remission rates in about 29% (CR+PR) of the patients while a total of 49% achieve improvement of blood counts.Revlimid® is also able to achieve complete remissions in advanced MDS and even overt leukemia with or without chromosome 5 abnormalities. Nevertheless, response rates are lower compared to low-risk MDS (IPSS Low/INT-1). Therefore, Revlimid® seems to be too weak as a single agent, but a promising compound for a combination therapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelodysplastic Syndromes, Acute Myelogenous Leukemia
Keywords
monosomy 5, del5q, lenalidomide, azacitidine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A

8. Arms, Groups, and Interventions

Arm Title
Azacitidine and Lenalidomide
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Azacitidine
Other Intervention Name(s)
Vidaza
Intervention Description
75 mg/m² SC days 1-5 every 28 days for a maximum of 8 cycles
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Other Intervention Name(s)
Revlimid
Intervention Description
10 - 25 mg PO days 6-19 every 28 days for a maximum of 8 cycles
Primary Outcome Measure Information:
Title
Maximum tolerated dose (MTD) of Revlimid® (lenalidomide)in combination with Vidaza®(5-azacitidine)
Time Frame
during first cycle of therapy
Secondary Outcome Measure Information:
Title
Clinical and cytogenetic response
Time Frame
during therapy
Title
Safety (type, frequency, severity, and relationship of adverse events to study treatment)
Time Frame
during therapy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Uwe Platzbecker, MD
Organizational Affiliation
Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medizinische Klinik und Poliklinik I, Uniklinik
City
Dresden
Country
Germany
Facility Name
Universitätsklinikum Düsseldorf, Klinik für Hämatologie/Onkologie/klinische Immunologie
City
Düsseldorf
ZIP/Postal Code
40225
Country
Germany
Facility Name
Klinikum der J.W. Goethe-Universität, Medizinische Klink II
City
Frankfurt
ZIP/Postal Code
60590
Country
Germany
Facility Name
Technische Universität München, Klinikum Rechts der Isar
City
München
ZIP/Postal Code
81675
Country
Germany

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs