Lenalidomide Maintenance Therapy in Patients With Myelodysplastic Syndromes (MDS) or Acute Myelogenous Leukemia (AML) (LENAMAINT)

This study has been terminated.
(Low recruitment, scientific rationale not applicable anymore to all patients and possible induction of GvHD by the study drug)
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Technische Universität Dresden
ClinicalTrials.gov Identifier:
NCT00720850
First received: July 17, 2008
Last updated: September 26, 2013
Last verified: September 2013
  Purpose

The hypothesis of this study is that lenalidomide can be an effective drug in preventing relapse of MDS and AML patients with chromosomal abnormalities involving monosomy 5 or del5q after allogeneic HSCT. Due to its immunomodulatory action it might also be able to enhance a T - or NK cell mediated graft versus leukemia (GVL) effects. Nevertheless, one has to keep in mind a possible, yet unknown influence on modulation of clinical GVHD.


Condition Intervention Phase
Myelodysplastic Syndromes
Acute Myelogenous Leukemia
Drug: lenalidomide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Lenalidomide Maintenance Therapy in Patients With MDS or AML With Cytogenetic Abnormalities Involving Monosomy 5 or del5q After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Resource links provided by NLM:


Further study details as provided by Technische Universität Dresden:

Primary Outcome Measures:
  • Cumulative incidence of relapse rate [ Time Frame: 1 year post transplantation ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival, Incidence and severity of acute and chronic GVHD, Safety [ Time Frame: 1 year post transplantation ] [ Designated as safety issue: Yes ]

Enrollment: 10
Study Start Date: April 2008
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: lenalidomide
lenalidomide therapy p.o. 10 mg/d for 21 days every 4 weeks for 1 year (12 cycles) after HSCT
Drug: lenalidomide
p.o. 10 mg/d for 21 days every 4 weeks for 1 year (12 cycles) after HSCT
Other Name: Revlimid

Detailed Description:

Cytogenetics are main predictors of outcome in patients with MDS and AML. In fact, a monosomy 5 (-5) or del5q (excluding typical 5q-syndrome) are mostly poor prognostic markers also because being frequently part of a complex karyotype. Together, these patients often do not respond to conventional chemotherapy and can only be cured by allogeneic HSCT. Nevertheless, even after transplantation the relapse rate is considerably high and in the majority of patient's relapses occur within the first year after HSCT.

Lenalidomide has been successfully used in MDS patients with del5q, irrespective of additional cytogenetic abnormalities. Furthermore, in vitro studies have demonstrated also impressive anti-proliferative effects of the compound in cell lines harbouring a monosomy 5. Therefore, it seems to be a promising compound in preventing relapse of high-risk MDS or AML patients with chromosomal abnormalities involving del5q or -5 after allogeneic HSCT. Due to its immunomodulatory action it might also be able to enhance T - or NK cell mediated graft versus leukemia effects. Nevertheless, it is unknown whether lenalidomide could modulate or enhance clinical graft versus host disease.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  • AML (>/= 20% blasts) including secondary (s)AML (after radio-chemotherapy) with karyotype abnormalities involving monosomy 5 or del5q or MDS and sMDS RAEB-1 and RAEB-2 with karyotype abnormalities involving monosomy 5 or del5q or MDS and sMDS type RA(+/-RS) or RCMD(+/-RS) only with complex karyotype abnormalities involving monosomy 5 or del5q
  • in complete hematological remission documented by bone marrow aspiration within 8-12 weeks after allogeneic HSCT
  • All previous cancer therapy, including radiation, hormonal therapy and surgery, must have been discontinued at least 4 weeks prior to treatment in this study.
  • ECOG performance status of </= 2 at study entry.
  • Laboratory test results within these ranges:

    • Absolute neutrophil count >= 1.0 x 10 9/L
    • Platelet count >= 100 x 10 9/L
    • Serum creatinine <= 2.0 mg/dL
    • Total bilirubin <= 1.5 mg/dL
    • AST (SGOT) and ALT (SGPT) <= 5 x ULN
  • Females of childbearing potential (FCBP)† must agree to use two reliable forms of contraception simultaneously 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. The two methods of reliable contraception must include one highly effective method (i.e. intrauterine device (IUD), hormonal [birth control pills, injections, or implants], tubal ligation, partner's vasectomy) and one additional effective (barrier) method (i.e. latex condom, diaphragm, cervical cap). FCBP must be referred to a qualified provider of contraceptive methods if needed.
  • Disease free of prior malignancies for >= 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast
  • Able to take aspirin (ASA) 100mg daily as prophylactic anticoagulation in case of concomitant steroid treatment (patients intolerant to ASA may use low molecular weight heparin).

Exclusion Criteria:

  • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
  • active uncontrolled acute GVHD overall grade 3-4
  • Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
  • History of arterial or venous embolism or stroke
  • 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.
  • Use of any other experimental drug or therapy to treat MDS or AML within 28 days of baseline (patients within a clinical trial evaluating new conditioning regimens are allowed to participate in the LENAMAINT study)
  • Known hypersensitivity to thalidomide or lenalidomide.
  • history of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
  • Known positive for HIV or infectious hepatitis, type A, B or C.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00720850

Locations
Germany
Dresden University of Technology, Medizinische Klinik und Poliklinik 1
Dresden, Saxony, Germany, 01307
Universitätsklinikum Düsseldorf, Medizinische Klinik und Poliklinik, Klinik für Hämatologie, Onkologie und klinische Immunologie
Düsseldorf, Germany, 40225
Universitätsklinikum Essen, Klinik für Knochenmarktransplantation
Essen, Germany, 45122
Universitätsklinikum Hamburg-Eppendorf, Onkologisches Zentrum
Hamburg, Germany, 20246
Medizinische Hochschule Hannover, Zentrum Innere Medizin, Hämatologie
Hannover, Germany, 30625
Universitätsklinikum Ulm, Klinik für Innere Medizin III
Ulm, Germany, 89081
Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II
Würzburg, Germany, 97080
Sponsors and Collaborators
Technische Universität Dresden
Celgene Corporation
Investigators
Study Chair: Uwe Platzbecker, PD Dr. med. Dresden University of Technology, Medizinische Klinik und Poliklinik 1
  More Information

Additional Information:
No publications provided

Responsible Party: Technische Universität Dresden
ClinicalTrials.gov Identifier: NCT00720850     History of Changes
Other Study ID Numbers: TUD-LENAMA-022
Study First Received: July 17, 2008
Last Updated: September 26, 2013
Health Authority: Germany: Ethics Commission
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Technische Universität Dresden:
MDS
AML
Lenalidomide
monosomy 5
monosomy del5q

Additional relevant MeSH terms:
Chromosome Aberrations
Chromosome Disorders
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Monosomy
Myelodysplastic Syndromes
Preleukemia
Pathologic Processes
Congenital Abnormalities
Genetic Diseases, Inborn
Neoplasms by Histologic Type
Neoplasms
Aneuploidy
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Lenalidomide
Thalidomide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents

ClinicalTrials.gov processed this record on April 22, 2014