Lenalidomide for Myelodysplastic Syndrome Refractory to Hypomethylating Agents

Study Overview
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Brief Summary
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The purpose of this study is to determine the proportion of confirmed responses (complete response, partial response, and hematologic improvement as defined by revised IWG criteria during the 12 months of treatment.

Official Title
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Phase II Trial of High Dose Lenalidomide in Patients With Myelodysplastic Syndrome Refractory to Hypomethylating Agents

Conditions
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Myelodysplastic Syndromes

Intervention / Treatment
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* Drug: Lenalidomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient must be able to understand and voluntarily sign an informed consent form. Patient must be ≥ 18 years old. Patient must be able to adhere to the study visit schedule and other protocol requirements. Patient must have histologically confirmed Myelodysplastic Syndrome as defined by FAB Classification including CMML and secondary MDS which has either: progressed at any time during treatment with hypomethylating agents failed to achieve a response after 6 cycles progressed after treatment with hypomethylating agents had been discontinued Criteria for response and for progression as defined by revised IWG criteria Patient must have discontinued all previous cancer therapy, including radiation, hormonal therapy and surgery at least 4 weeks prior to treatment in this study. Patient must have an ECOG performance status of ≤ 2 at study entry Patient must have laboratory test results within these ranges: calculated creatinine clearance ≥ 30ml/min by Cockcroft-Gault formula total bilirubin ≤ 1.5 x ULN AST (SGOT) and ALT (SGPT) ≤ 3 x ULN Patient must be disease free of prior malignancies for at least 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix or breast. Patient must be registered into the mandatory Revlimid REMS® program and be willing and able to comply with the requirements of Revlimid REMS®. If a female of childbearing potential (FCBP), patient must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 to 14 days prior to initiation of therapy and again within 24 hours prior to prescribing lenalidomide for Cycle 1 (prescriptions must be filled within 7 days). Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program. A FCBP is defined as a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months). -If a FCBP, patient 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 Exclusion Criteria: Patient must not have any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form. Patient must not be pregnant or breastfeeding. Patient must not have 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. Patient must not use any other experimental drug or therapy within 28 days of baseline. Patient must not have a known hypersensitivity to thalidomide. Patient must not have developed of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs. Patient must not have any prior use of lenalidomide. Patient must not be concurrently using other anti-cancer agents or treatments. Patient must not have known seropositivity for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine are eligible.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lenalidomide<br>Lenalidomide 50 mg/day for two 28 day cycles. Patients who have bone marrow aplasia as defined by a cellularity of <10% will be observed till counts recover. If patients do not progress following 2 cycles of HD lenalidomide, they will receive low dose lenalidomide 10 mg daily for 12 cycles. | Drug: Lenalidomide<br> <br> * Other names: Revlimid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Confirmed Responses (Complete Remission, Partial Remission, or Hematologic Improvement) as Defined by the International Working Group Criteria | Complete remission (CR): ≤5% myeloblasts bone marrow blasts, normal maturation in all cell lines (dysplasia will be noted), ≥11 g/dl peripheral blood hemoglobin, ≥100x10^9cells/μL peripheral blood platelets, ≥1000 cells/ μL peripheral blood absolute neutrophil count (ANC), and 0% peripheral blood blasts. Marrow complete remission (MCR): ≤5% myeloblasts and decreased by ≥50% compared to pre-treatment bone marrow blasts, bone marrow morphology not relevant, and peripheral blood (if hematological improvement they will be noted in addition to marrow CR). Partial remission (PR): previously had ≥5% myeloblasts and now have ≥5% myeloblasts but decreased by ≥50% compared to pre-treatment, bone marrow morphology not relevant, ≥11 g/dl peripheral blood hemoglobin, ≥100x109cells/μL peripheral blood platelets, ≥1000 cells/ μL peripheral blood ANC, and 0% peripheral blood blasts | Up to 56 weeks (14 cycles of treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival Rate | -Overall survival rate is the percentage of participants who were alive 6 months after end of treatment. | 6 months after end of treatment (up to 82 weeks from start of treatment) | 
| Duration of Response |  | Until 6 months after end of treatment | 
| Time to Discontinuation of Treatment |  | Up to 56 weeks (14 cycles) | 
| Toxicity as Measured by Number of Participants Who Experienced Related Grade 3-5 Adverse Events Based on CTCAE Version 4 |  | 30 days after end of treatment (up to 60 weeks) | 
| Time to Progression | The time to progression is defined as the time from registration to the date of progression or last follow-up. Those who die will be considered to have had disease progression unless documented evidence clearly indicates no progression has occurred. | Up to 6 months after completion of treatment (up to 82 weeks from start of treatment) |