Trial of High Dose Lenalidomide in Patients With MDS and AML With Trilineage Dysplasia

Phase 2

Terminated

Brief Summary: This is a phase II study of lenalidomide in patients with myelodysplastic syndrome (MDS) and with acute myeloid leukemia (AML) with trilineage dysplasia. Patients will receive two cycles of lenalidomide. Patients who respond may given additional cycles of lenalidomide until disease progression.

Detailed Description: This is a single center open label phase II study of lenalidomide in IPSS Int-1 with increased blasts or hematologic needs with 5q31.1 deletions who have failed to respond to standard dose lenalidomide., IPSS Int-1 with increased blasts or hematologic needs without 5q31.1 deletions, and Int-2 and high risk myelodysplastic syndrome (MDS) patients with or without 5q31.1 deletions, regardless of whether they have received lenalidomide previously or not. Patients will receive two cycles of 15 mg daily lenalidomide (later amended to 50 mg daily lenalidomide) given on days 1-28 out of a 42 day cycle. Within each of the two cycles of lenalidomide, patients will be given up to three weeks with no drug treatment to recover. Patients who fail to respond after two cycles of treatment may receive two additional cycles if stable. Patients who develop clinical response may continue to receive drug until disease progression.

Recruitment & Eligibility

Inclusion Criteria

Age greater than 18 years at the time of signing the informed consent form.
Able to adhere to the study visit schedule and other protocol requirements.
MDS or MDS/AML
Patients must not have received any other treatment for their disease, including hematopoietic growth factors, within three weeks of beginning the trial
ECOG performance status of 0, 1, or 2 at study entry
All study participants must be registered into the mandatory REMS® program, and be willing and able to comply with the requirements of RevAssist®.
Patients must have no clinical evidence of CNS or pulmonary leukostasis, disseminated intravascular coagulation, or CNS leukemia.
Subjects must agree to use appropriate contraception.

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 taking lenalidomide).
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 within 21 days of baseline.
Known hypersensitivity to thalidomide.
The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
Any prior use of lenalidomide except for MDS patients with del 5q31.1 abnormalities..
Concurrent use of other anti-cancer agents or treatments.
Patients may not have received prior AML induction chemotherapy or stem cell transplant. However, patients with secondary MDS who have received a stem cell transplant for other indications (eg lymphoma, multiple myeloma) will be eligible.

Arm && Interventions

Group	Intervention	Description
Lenalidomide 15 mg	Lenalidomide 15 mg	Patients diagnosed with high risk Myelodysplastic syndrome (MDS), regardless of 5q deletion status, will receive lenalidomide 15 mg per day orally, on days 1-28 of a 42 day cycle for 2 cycles. At this point, patients meeting protocol specified response criteria will proceed to Continuing Therapy on a reduced dose of lenalidomide until progression. Patients not achieving response will receive 2 additional cycles of treatment, whereupon response will again be assessed. Patients achieving response at this point will proceed to Continuing Therapy as described. Patients without evidence of response after 4 cycles will be taken off-study.
Lenalidomide 50 mg	Lenalidomide 50 mg	Patients diagnosed with high risk Myelodysplastic syndrome (MDS), regardless of 5q deletion status, will receive lenalidomide 50 mg per day orally, on days 1-28 of a 42 day cycle for 2 cycles. At this point, patients meeting protocol specified response criteria will proceed to Continuing Therapy on a reduced dose of lenalidomide until progression. Patients not achieving response will receive 2 additional cycles of treatment, whereupon response will again be assessed. Patients achieving response at this point will proceed to Continuing Therapy as described. Patients without evidence of response after 4 cycles will be taken off-study.

Primary Outcome Measures

Name	Time	Method
Response Rate	15 weeks	Number of participants with a complete or partial response according to International Working Group 2006 criteria.

Secondary Outcome Measures

Name	Time	Method
Grade 3-4 Toxicity	Up to 8 months	Number of participants who experienced at least one grade 3-4 non-hematological toxicity by CTCAE 3.0 that was attributed to lenalidomide.