Lenalidomide After Failure of Hypomethylating Agents in Myelodysplastic Syndrome (VIOLET)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2012 by Ulsan University Hospital
Sponsor:
Collaborator:
Cooperative Study Group A for Hematology
Information provided by (Responsible Party):
Hawk Kim, Ulsan University Hospital
ClinicalTrials.gov Identifier:
NCT01673308
First received: August 22, 2012
Last updated: September 17, 2012
Last verified: September 2012
  Purpose

This is a Phase II study to evaluate the efficacy of second-line lenalidomide monotherapy for myelodysplastic syndrome (MDS) patients who failed to hypomethylating agents.


Condition Intervention Phase
Myelodysplastic Syndrome
Drug: Lenalidomide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Salvage in Patients With Myelodysplastic Syndrome After Failure of Hypomethylating Agents: Lenalidomide as a Second-line Therapy

Resource links provided by NLM:


Further study details as provided by Ulsan University Hospital:

Primary Outcome Measures:
  • Response criteria by international working group (IWG) 2006 criteria [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Safety assessed by national cancer institute (NCI) common terminology criteria for adverse events (CTCAE) version 4.03


Estimated Enrollment: 35
Study Start Date: August 2012
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment arm
Lenalidomide treatment arm
Drug: Lenalidomide
Lenalidomide 10 mg orally on days 1 to 21 of a 28-day cycle for at least 4 cycles until intolerance or disease progression.
Other Name: Revlimid

Detailed Description:

There is no standard therapy after the failure of hypomethylating agents only providing supportive cares including transfusion or cytokine therapies. Lenalidomide is the treatment of choice in case of MDS with 5q deletion. A study of lenalidomide for non-5q deletion MDS patients showed that transfusion independency rate was 26% which was relatively acceptable and suggested that lenalidomide could be used for non-5q deletion MDS patients. There is no datum for second-line lenalidomide therapy after hypomethylating agents. MDS which has highly complex pathogenesis backgrounds will have distinctive subtype for each therapy and each treatment drug can have distinctive subgroup for the response. In fact the investigators don't know which patient will be responsive hypomethylating agents or lenalidomide except for 5q deletion. This suggests that second line therapy after the first line failure in MDS will be different with other type of relapsed/refractory disease which will be tend to more resistant to subsequent therapies. In this regard, there is a possibility to have a relatively high response rate to second line lenalidomide in this selected subset who has failed to the hypomethylation therapy or some patients will be responsive regardless of treatment line. Recent data suggested that MDS with JAK2 mutation will be responsive to lenalidomide. The investigators will analyze the JAK2 mutation status in response evaluation.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Myelodysplastic syndrome by world health organization (WHO) classification
  • Treatment failure after hypomethylating agents (HMA; azacitidine or decitabine); Intolerant to hypomethylating agents or Progressive disease after HMA
  • Age over 18 years old
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤2
  • Adequate organ function (serum creatinine ≤ 2.5 mg/dL, serum aspartate transaminase or alanine transaminase ≤ 3.0 x upper limit of normal (ULN), and serum direct bilirubin ≤ 2.0 mg/dL).

Exclusion Criteria:

  • Previous therapy history for MDS except for hypomethylating agents, cytokines (granulocyte-stimulating agents or erythropoietin) or supportive care.
  • Patients who cannot keep the strict contraception or who willing to be pregnant.
  • Contraindication to lenalidomide: Females who are or may become pregnant; Lenalidomide is contraindicated in any patients who have demonstrated hypersensitivity to the drug or its components; Lenalidomide capsules contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
  • Patients who cannot take lenalidomide orally
  • Current enrollment to other clinical trial
  • Presence of uncontrolled bleeding
  • Severe or life-threatening other medical conditions
  • Any coexisting major illness or organ failure
  • Patients with psychiatric disorder or mental deficiency severe as to make compliance with the treatment unlike, and making informed consent impossible
  • History of congenital or acquired coagulopathy unrelated to malignancy
  • History of non-compliance or patient who cannot sign informed consent
  • Patients with a diagnosis of prior malignancy unless disease-free for at least 5 years following therapy with curative intent (except curatively treated nonmelanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia)
  • Candidate of hematopoietic stem cell transplantation who cannot complete 4 cycles of lenalidomide.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01673308

Contacts
Contact: Hawk Kim, M.D., Ph.D. +82-52-250-8892 kimhawkmd@gmail.com

Locations
Korea, Republic of
Ulsan University Hospital Recruiting
Ulsan, Korea, Republic of, 682714
Contact: Hawk Kim, M.D., Ph.D.    +82-52-250-8892    kimhawkmd@gmail.com   
Principal Investigator: Hawk Kim, M.D., Ph.D.         
Sub-Investigator: Jae-Hoo Park, M.D., Ph.D.         
Sponsors and Collaborators
Ulsan University Hospital
Cooperative Study Group A for Hematology
Investigators
Principal Investigator: Hawk Kim, M.D., Ph.D. Ulsan University Hospital, University of Ulsan College of Medicine
  More Information

Publications:
Prebet T, Gore SD, Esterni B, et al. Outcome of high-risk myelodysplastic syndrome after azacitidine treatment failure. J Clin Oncol. 2011;29:3322-3327.
Jabbour E, Garcia-Manero G, Batty N, et al. Outcome of patients with myelodysplastic syndrome after failure of decitabine therapy. Cancer. 2010;116:3830-3834
Heise C, Carter T, Schafer P, Chopra R. Pleiotropic mechanisms of action of lenalidomide efficacy in del(5q) myelodysplastic syndromes. Expert Rev Anticancer Ther. 2010;10:1663-1672
Nomdedeu M, Maffioli M, Calvo X, et al. Efficacy of lenalidomide in a patient with myelodysplastic syndrome with isolated del(5q) and JAK2(V617F) mutation. Leuk Res. 2011;35:1276-1278

Responsible Party: Hawk Kim, Associate Professor, Ulsan University Hospital
ClinicalTrials.gov Identifier: NCT01673308     History of Changes
Other Study ID Numbers: RV-MDS-PI-0722
Study First Received: August 22, 2012
Last Updated: September 17, 2012
Health Authority: Korea: Food and Drug Administration

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Lenalidomide
Thalidomide
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on August 18, 2014