A Study of Lenalidomide Versus Placebo in Subjects With Transfusion Dependent Anemia in Low Risk Myelodysplastic Syndrome (MDS) Without Del 5Q (MDS-005)

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2009-011513-24-DE
• Date of registration: 02/11/2009
• Prospective Registration: Yes
• Primary sponsor: Celgene Corporation
• Public title: A Study of Lenalidomide Versus Placebo in Subjects With Transfusion Dependent Anemia in Low Risk Myelodysplastic Syndrome (MDS) Without Del 5Q (MDS-005)
• Scientific title: A PHASE 3, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP STUDY TO COMPARE THE EFFICACY AND SAFETY OF LENALIDOMIDE (REVLIMID®) VERSUS PLACEBO IN SUBJECTS WITH TRANSFUSION-DEPENDENT ANEMIA DUE TO IPSS LOW OR INTERMEDIATE-1 RISK MYELODYSPLASTIC SYNDROMES WITHOUT DELETION 5Q[31] AND UNRESPONSIVE OR REFRACTORY TO ERYTHROPOIESISSTIMULATING AGENTS
• Target sample size: 228
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-011513-24
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Belgium, Czech Republic, France, Germany, Israel, Italy, Poland, Portugal, Spain, Turkey, United Kingdom

Contacts

• Name: ClinicalTrialDisclosure
• Affiliation: Celgene Corporation

• Name: ClinicalTrialDisclosure
• Affiliation: Celgene Corporation

Key inclusion & exclusion criteria

Inclusion criteria:
1.Must understand and voluntarily sign an informed consent form.
2.Age = 18 years at the time of signing the informed consent form.
3.Must be able to adhere to the study visit schedule and other protocol requirements including willingness to undergo bone marrow aspirate and biopsy as indicated in the study protocol.
4.Must be able to complete patient-reported outcome assessments either independently or with minimal assistance from trained clinic personnel or caregiver.
5.Must have a documented diagnosis of MDS according to WHO 2008 classification (Brunning, 2008) associated with the following features:
- IPSS low or intermediate-1 risk (subjects who were once a higher risk
IPSS are excluded)
- Any karyotype except del 5q [31] (at least 20 analyzable metaphases are required for standard G-banding cytogenetic analysis at screening).
6.Must have transfusion-dependent anemia that meets the following criteria:
- Average transfusion requirement of =2 units‡/28 days of pRBCs confirmed for a minimum of 112 days immediately preceding randomization.
- No consecutive 56 days that was RBC transfusion-free during the 112 days immediately preceding randomization.
- Hemoglobin levels at the time of or within 7 days prior to transfusions must have been = 9.0 g/dL for the transfusions to qualify as required for the purpose of providing evidence of transfusion-dependent anemia
7.Must be unresponsive or refractory to erythropoiesis-stimulating agents, based on one of the following two criteria:
- Transfusion-dependence in subjects previously treated with an ESA (requires a minimum ESA trial of > 40,000 U/week r-HuEPO x 8 weeks or equivalent dose of darbepoetin or other erythropoietin agent), or
- Serum erythropoietin level of > 500 mU/mL in subjects not previously treated with an ESA.
8.Must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.
9.Concurrent corticosteroids used for medical conditions other than MDS is allowed provided subject is on a stable or decreasing dose for = 1 week prior to randomization.
10.Females of childbearing potential (FCBP) must undergo pregnancy testing based on the frequency outlined in Appendices 21.2 and 21.4 and pregnancy results must be negative.
11.Unless practicing complete abstinence from heterosexual intercourse, sexually active FCPB must agree to use adequate contraceptive methods as specified in Appendices 21.2 and 21.4.
12.Males (including those who have had a vasectomy) must use barrier contraception (condoms) when engaging in sexual activity with FCBP as specified Appendices 21.2 and 21.4.
13.Males must agree not to donate semen or sperm during the duration specified in Appendices 21.2 and 21.4.
14. All subjects must:
- Understand that the investigational product could have a potential teratogenic risk.
- Agree to abstain from donating blood while taking investigational product and following discontinuation of investigational product (see Appendices 21.2 and 21.4)
- Agree not to share investigational product with another person.
- Be cou
Exclusion criteria:
1.Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
2.Pregnant or lactating females.
3.Prior history of malignancies, other than MDS, unless the subject has been free of the disease for = 5 years. However, subjects with the following history/concurrent conditions may enroll at any time:
- Basal cell carcinoma of the skin
- Carcinoma in situ of the cervix
- Incidental histologic finding of prostate cancer (Tumor Node Metastasis (TNM) stage of T1a or T1b)
4. Known Human Immunodeficiency Virus (HIV), active Hepatitis B
Virus (HBV) and/or Hepatitis C Virus (HCV) infection.
5. Prior therapy with immunomodulating or immunosuppressive agents,
or epigenetic or DNA modulating agents. Subjects who received
investigational agents are also excluded.
6. Any of the following laboratory abnormalities:
- Absolute neutrophil count (ANC) < 500/µL (0.5 x 109/L)
- Platelet count < 50,000/µL (50 x 109/L)
- Serum aspartate aminotransferase (AST)/serum glutamic-oxaloacetic
transaminase (SGOT) or alanine transaminase (ALT)/serum glutamate
pyruvate transaminase (SGPT) > 3.0 x upper limit of normal (ULN) o
serum bilirubin levels > 1.5 x ULN; serum bilirubin levels > 1.5 x ULN
are acceptable if these can be attributed to ineffective erythropoiesis.
Subjects with ineffective erythropoiesis may have a decreased
haptoglobin level, elevated indirect bilirubin level and/or lactate
dehydrogenase level (refer to Appendix 21.10). Autoimmune hemolytic
anemia is an exclusion criterion.
7. Renal insufficiency (CrCl < 40 mL/min by Cockroft-Gault method)
8. Uncontrolled hyperthyroidism or hypothyroidism.
9. = Grade-2 neuropathy.
10. Use of an erythropoiesis stimulating agent within the 56 days prior
to randomization.
11. Prior allogeneic or autologous stem cell transplantation.
12. Concurrent use of androgens other than to treat hypogonadism.
13. Clinically significant anemia due to iron, B12, or folate deficiencies,
or autoimmune or hereditary hemolytic anemia, or gastrointestinal
bleeding.
*If marrow stain for iron is not available, the transferrin saturation
(iron/total iron binding capacity Fe/TIBC) must be >20% or serum
ferritin must be >100 ng/dL
14. Prior history of deep venous thrombosis (DVT) or pulmonary
embolus (PE) within 3
years of randomization.
15. Significant active cardiac disease within the previous 6 months
including:
- New York Heart Association class II-IV congestive heart failure
- Unstable angina or angina requiring surgical or medical intervention
- Myocardial infarction



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

TRANSFUSION-DEPENDENT ANEMIA DUE TO IPSS LOW OR INTERMEDIATE-1 RISK MYELODYSPLASTIC SYNDROMES WITHOUT DELETION 5Q [31] AND UNRESPONSIVE OR REFRACTORY TO ERYTHROPOIESIS-STIMULATING AGENT
MedDRA version: 18.1 Level: LLT Classification code 10068361 Term: MDS System Organ Class: 100000004864

Intervention(s)

Trade Name: Revlimid 2.5mg, hard capsules
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: LENALIDOMIDE
CAS Number: 191732-72-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Revlimid 5mg, hard capsules
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: LENALIDOMIDE
CAS Number: 191732-72-6
Current Sponsor code: CC-5013
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Revlimid 10mg, hard capsules
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: LENALIDOMIDE
CAS Number: 191732-72-6
Current Sponsor code: CC-5013
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Up to 6 years for each subject (likely to be 6 months to 2 years)

Secondary Objective: •To evaluate the safety of lenalidomide versus placebo in subjects with RBC transfusion-dependent low or Int-1 risk MDS associated with any karyotype except deletion 5q[31] and unresponsive or refractory to erythropoiesisstimulating agents.

•To evaluate the impact of lenalidomide therapy on health-related quality of life (HRQOL) and healthcare resource utilization.

Main Objective: To compare the efficacy of lenalidomide versus placebo in subjects with red blood cell (RBC) transfusiondependent low or Int-1 risk MDS associated with any karyotype except deletion 5q[31] and unresponsive or refractory to erythropoiesis-stimulating agents in the ITT population and in the pre-specified subgroup of subjects with an erythroid differentiation signature predictive of lenalidomide response

Primary end point(s): Proportion of subjects in the
- ITT population and in the
- pre-specified subgroup of subjects with an erythroid differentiation gene expression signature predictive of lenalidomide response (Ebert, 2008) achieving red blood cell (RBC) transfusion independence for at least 8 weeks (using International Working Group (IWG) 2006 criteria)

Secondary Outcome(s)

Secondary end point(s): Evaluate the safety of lenalidomide versus placebo. [ Time Frame: at least 6 years from study start through follow-up ]

Evaluate the impact of lenalidomide therapy on health-related quality of life (HRQOL) and use of healthcare resources. [ Time Frame: at least 6 years from study start through follow-up ]

Timepoint(s) of evaluation of this end point: See E.5.2

Secondary ID(s)

CC-5013-MDS-005

2009-011513-24-BE

Source(s) of Monetary Support

Celgene Corporation

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 24/05/2019
• Date Completed: 09/05/2018
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-011513-24/results