The purpose of the study is to determine if the drug lenalidomide (Revlimid®) is able to improve anaemia (low red blood count) and reduce the number of blood transfusions that you require because of Myelodysplastic Syndrome (MDS). The other purpose of the study is to evaluate the effect of the study drug (lenalidomide) on the genetic abnormality (changes in the cell characteristics) associated with MDS.

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2004-005101-29-GB
• Date of registration: 23/02/2005
• Prospective Registration: Yes
• Primary sponsor: King's College Hospital NHS Foundation Trust
• Public title: The purpose of the study is to determine if the drug lenalidomide (Revlimid®) is able to improve anaemia (low red blood count) and reduce the number of blood transfusions that you require because of Myelodysplastic Syndrome (MDS). The other purpose of the study is to evaluate the effect of the study drug (lenalidomide) on the genetic abnormality (changes in the cell characteristics) associated with MDS.
• Scientific title: THE EFFICACY AND SAFETY OF LENALIDOMIDE (Revlimid®) MONOTHERAPY IN RED BLOOD CELL TRANSFUSION DEPENDENT SUBJECTS WITH MYELODYSPLASTIC SYNDROME ASSOCIATED WITH A DEL (5q) CYTOGENETIC ABNORMALITY - Revlimid in MDS with 5q- cytogenetic abnormality
• Date of first enrolment: 24/02/2005
• Target sample size: 48
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2004-005101-29
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

United Kingdom

Contacts

• Name: Professor Ghulam Mufti
• Affiliation: King's College Hospital NHS Foundation Trust

• Name: Professor Ghulam Mufti
• Affiliation: King's College Hospital NHS Foundation Trust

Key inclusion & exclusion criteria

Inclusion criteria:
1. Understand and voluntarily sign an informed consent form.
2. Age >18 years at the time of signing the informed consent form.
3. Able to adhere to the study visit schedule and other protocol requirements.
4. Diagnosis of low- or intermediate-1-risk (IPSS) MDS associated with a del(5q) cytogenetic abnormality. The del(5q) cytogenetic abnormality may be an isolated finding or may be associated with other cytogenetic abnormalities and if del5q is an isolated aberration the patient could have up to 20% blasts.
5. RBC transfusion-dependent anaemia defined as having at least 2 separate transfusion events within the past 112 days.
6. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2 (Appendix I).
7. Women of childbearing potential (WCBP)† must:
o Understand the study drug is expected to have a teratogenic risk
o Agree to use, and be able to comply with, effective contraception without interruption, 4 weeks before starting study drug, throughout the entire duration of study drug therapy (including dose interruptions) and for 4 weeks after the end of study drug therapy, even if she has amenorrhoea. This applies unless the subject commits to absolute and continued abstinence confirmed on a monthly basis. The following are effective methods of contraception
o Implant
o Levonorgestrel-releasing intrauterine system (IUS)
o Medroxyprogesterone acetate depot
o Tubal sterilisation
o Sexual intercourse with a vasectomised male partner only; vasectomy must be confirmed by two negative semen analyses
o Ovulation inhibitory progesterone-only pills (i.e., desogestrel)
o Understand that even if she has amenorrhea, she must follow all the advice on effective contraception.She understands the potential consequences of pregnancy and the need to rapidly consult if there is a risk of pregnancy
o Agree to have medically supervised pregnancy test with a minimum sensitivity of 25 mIU/ml between 14 and 10 days prior to starting drug therapy. In addition, agree to have a medically supervised pregnancy test with a minimum sensitivity of 25 mIU/ml on the day of drug dispensing (prior to starting drug therapy) or within the 24 hours prior to the study visit once the subject has been on effective contraception for at least 4 weeks. This requirement also applies to women of childbearing potential who practice complete and continued abstinence. The test should ensure the subject is not pregnant when she starts treatment
o WCBP must undergo pregnancy testing at intervals described in Appendix 4. These pregnancy tests should be performed on the day of drug dispensing (prior to prescribing lenalidomide) or within the 24 hours prior to the study visit. This requirement also applies to women of childbearing potential who practice complete and continued abstinence
• Male subjects must
o Agree to use condoms throughout study drug therapy, during any dose interruption and for one week after cessation of study drug therapy if their partner is of childbearing potential and has no contraception.
o Agree not to donate semen or sperm during study drug therapy and for 28 days after end of study drug therapy.

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 > grade 3 (National Cancer Institute [NCI] Common Toxicity Criteria [CTC]) allergic reaction to thalidomide (Appendix 3).
4. Prior > grade 3 (NCI CTC) rash or any desquamation (blistering) while taking thalidomide (Appendix 3).
5. Clinically significant anaemia due to factors such as iron, B12 or folate deficiencies, autoimmune or hereditary haemolysis or gastrointestinal bleeding (if a marrow aspirate is not evaluable for storage iron, transferrin saturation must be > 20 % and serum ferritin not less than 50 ng/ml).
6. Use of haematopoietic growth factors within 7 days of the first day of study drug treatment. Use of G-CSF is permitted.
7. Concurrent use of erythropoietin
8. Chronic use (>2 weeks) of greater than physiologic doses of a corticosteroid agent (dose equivalent to >10 mg/day of prednisolone) within 28 days of the first day of study lenalidomide treatment.
9. Use of experimental or standard drugs (i.e. chemotherapeutic, immunosuppressive, and cytoprotective agents) for the treatment of MDS within 28 days of the first day of study lenalidomide treatment.
10. Prior history of malignancy other than MDS (except basal cell or squamous cell carcinoma or carcinoma in situ of the cervix or breast) unless the subject has been free of disease for >5 years.
11. Any prior use of lenalidomide
12. Concurrent use of other anti-cancer agents or treatments. Patients must not have received any form of chemotherapy for at least 4 weeks prior to study entry and must have fully recovered from haematological toxicity associated with this therapy.
13. Known positive for HIV or infectious hepatitis, type A, B or C.


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]

Myelodysplastic Syndrome (MDS) associated with a Del (5q) cytogenetic abnormality
MedDRA version: 16.0 Level: LLT Classification code 10067097 Term: 5q minus MDS System Organ Class: 100000004864

Intervention(s)

Trade Name: Revlimid
Product Name: Revlimid®
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: LENALIDOMIDE
CAS Number: 191732-72-6
Other descriptive name: Revlimid
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Primary Outcome(s)

Secondary Objective: To evaluate the safety of lenalidomide treatments in MDS subjetcs with a del5q cytogenetic abnormality.
To attempt to determine further the genetic and cellular changes involved with the development of the 5q- syndrome and the effects of lenalidomide (Revlimid®) upon these cells

Primary end point(s): Red blood cell (RBC) transfusion independence.

Main Objective: To evaluate the efficacy of lenalidomide treatments to achieve haematopoietic improvement in subjects with low- or intermediate-1 risk International Prognostic Scoring System1 (IPSS) myelodysplastic syndrome (MDS) associated with a del 5q cytogenetic abnormality
To evaluate the efficacy of lenalidomide to achieve haematopoietic improvement in patients with isolated del5q with blasts <20%

Timepoint(s) of evaluation of this end point: Subjects may remain in the study until bone marrow disease progression or progression/relapse following erythroid haematological improvement

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Subjects may remain in the study until bone marrow disease progression or progression/relapse following erythroid haematological improvement

Secondary end point(s): • Cytogenetic response
• >50 % decrease in RBC transfusion requirements
• Change of haemoglobin concentration from baseline
• Safety (type, frequency, severity, and relationship of adverse events to lenalidomide)
• Platelet response
• Neutrophil response
• Bone marrow response
• Duration of response
• Gene expression profiling of patients with the 5q- syndrome and effects of lenalidomide on gene expression profiles.

Secondary ID(s)

KCH-MDS-04-1.0

Source(s) of Monetary Support

King's College Hospital NHS Foundation Trust

Secondary Sponsor(s)

King's College London

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 21/09/2019
• Date Completed: 23/05/2016
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2004-005101-29/results