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

Primary Purpose

Myelodysplastic Syndrome

Status

Unknown status

Phase

Phase 2

Locations

Korea, Republic of

Study Type

Interventional

Intervention

Lenalidomide

About this trial

This is an interventional treatment trial for Myelodysplastic Syndrome

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Ulsan University Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment arm

Arm Description

Lenalidomide treatment arm

Outcomes

Primary Outcome Measures

Response criteria by international working group (IWG) 2006 criteria

Secondary Outcome Measures

Safety

Safety assessed by national cancer institute (NCI) common terminology criteria for adverse events (CTCAE) version 4.03

Full Information

NCT ID

NCT01673308

First Posted

August 22, 2012

Last Updated

May 10, 2016

Sponsor

Ulsan University Hospital

Collaborators

Cooperative Study Group A for Hematology

1. Study Identification

Unique Protocol Identification Number

NCT01673308

Brief Title

Lenalidomide After Failure of Hypomethylating Agents in Myelodysplastic Syndrome

Acronym

VIOLET

Official Title

Salvage in Patients With Myelodysplastic Syndrome After Failure of Hypomethylating Agents: Lenalidomide as a Second-line Therapy

Study Type

Interventional

2. Study Status

Record Verification Date

May 2016

Overall Recruitment Status

Unknown status

Study Start Date

August 2012 (undefined)

Primary Completion Date

November 2015 (Actual)

Study Completion Date

November 2016 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Ulsan University Hospital

Collaborators

Cooperative Study Group A for Hematology

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Myelodysplastic Syndrome

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

35 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Treatment arm

Arm Type

Experimental

Arm Description

Lenalidomide treatment arm

Intervention Type

Drug

Intervention Name(s)

Lenalidomide

Other Intervention Name(s)

Revlimid

Intervention Description

Lenalidomide 10 mg orally on days 1 to 21 of a 28-day cycle for at least 4 cycles until intolerance or disease progression.

Primary Outcome Measure Information:

Title

Response criteria by international working group (IWG) 2006 criteria

Time Frame

12 months

Secondary Outcome Measure Information:

Title

Safety

Description

Safety assessed by national cancer institute (NCI) common terminology criteria for adverse events (CTCAE) version 4.03

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Hawk Kim, M.D., Ph.D.

Organizational Affiliation

Ulsan University Hospital, University of Ulsan College of Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Ulsan University Hospital

City

Ulsan

ZIP/Postal Code

682714

Country

Korea, Republic of

12. IPD Sharing Statement

Citations:

PubMed Identifier

21788559

Citation

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Results Reference

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PubMed Identifier

20564137

Citation

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Results Reference

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PubMed Identifier

15703420

Citation

List A, Kurtin S, Roe DJ, Buresh A, Mahadevan D, Fuchs D, Rimsza L, Heaton R, Knight R, Zeldis JB. Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med. 2005 Feb 10;352(6):549-57. doi: 10.1056/NEJMoa041668.

Results Reference

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PubMed Identifier

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Citation

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PubMed Identifier

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Citation

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Results Reference

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PubMed Identifier

20942636

Citation

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 Oct;10(10):1663-72. doi: 10.1586/era.10.135.

Results Reference

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PubMed Identifier

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Citation

Nomdedeu M, Maffioli M, Calvo X, Martinez-Trillos A, Baumann T, Diaz-Beya M, Aguilar JL, Rozman M, Costa D, Esteve J, Cervantes F, Colomer D, Nomdedeu B. Efficacy of lenalidomide in a patient with myelodysplastic syndrome with isolated del(5q) and JAK2V617F mutation. Leuk Res. 2011 Sep;35(9):1276-8. doi: 10.1016/j.leukres.2011.06.008. Epub 2011 Jul 20. No abstract available.

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Citation

Raza A, Reeves JA, Feldman EJ, Dewald GW, Bennett JM, Deeg HJ, Dreisbach L, Schiffer CA, Stone RM, Greenberg PL, Curtin PT, Klimek VM, Shammo JM, Thomas D, Knight RD, Schmidt M, Wride K, Zeldis JB, List AF. Phase 2 study of lenalidomide in transfusion-dependent, low-risk, and intermediate-1 risk myelodysplastic syndromes with karyotypes other than deletion 5q. Blood. 2008 Jan 1;111(1):86-93. doi: 10.1182/blood-2007-01-068833. Epub 2007 Sep 24.

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Results Reference

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Lenalidomide After Failure of Hypomethylating Agents in Myelodysplastic Syndrome

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