Lenalidomide for Myelodysplastic Syndrome Refractory to Hypomethylating Agents

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

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.

Study Overview

• Status: Completed
• Conditions: Myelodysplastic Syndromes
• Intervention / Treatment: Drug: Lenalidomide

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States
      • Mayo Clinic Scottsdale AZ
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lenalidomide; 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; Other Names: Revlimid

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Washington University School of Medicine

Publications and helpful links

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: November 15, 2010
• First Submitted That Met QC Criteria: November 22, 2010
• First Posted (Estimate): November 23, 2010

Study Record Updates

• Last Update Posted (Estimate): January 5, 2016
• Last Update Submitted That Met QC Criteria: November 30, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Lenalidomide
• Other Study ID Numbers: 201011810