Lenalidomide Maintenance Therapy in Patients With MDS or AML With Cytogenetic Abnormalities Involving Monosomy 5 or del5q After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
Overview
- Phase
- Phase 2
- Intervention
- lenalidomide
- Conditions
- Myelodysplastic Syndromes
- Sponsor
- Technische Universität Dresden
- Enrollment
- 10
- Locations
- 7
- Primary Endpoint
- Cumulative incidence of relapse rate
- Status
- Terminated
- Last Updated
- 12 years ago
Overview
Brief Summary
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.
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.
Investigators
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.
- •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
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.
Arms & Interventions
lenalidomide
lenalidomide therapy p.o. 10 mg/d for 21 days every 4 weeks for 1 year (12 cycles) after HSCT
Intervention: lenalidomide
Outcomes
Primary Outcomes
Cumulative incidence of relapse rate
Time Frame: 1 year post transplantation
Secondary Outcomes
- Overall survival, Incidence and severity of acute and chronic GVHD, Safety(1 year post transplantation)