Clinical Trials Register

Summary
EudraCT Number:	2004-005101-29
Sponsor's Protocol Code Number:	KCH-MDS-04-1.0
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2005-02-23
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2004-005101-29

A.3

Full title of the trial

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

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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.

A.3.2

Name or abbreviated title of the trial where available

Revlimid in MDS with 5q- cytogenetic abnormality

A.4.1

Sponsor's protocol code number

KCH-MDS-04-1.0

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	King's College Hospital NHS Foundation Trust
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	King's College Hospital NHS Foundation Trust
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	King's College Hospital NHS Foundation Trust
B.5.2	Functional name of contact point	Professor Ghulam Mufti
B.5.3	Address:
B.5.3.1	Street Address	Department of Haematological Medicine, King's College Hospital, Denmark Hill
B.5.3.2	Town/ city	London
B.5.3.3	Post code	SE5 9RS
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	00440203299 3080
B.5.5	Fax number	00440207346 3514
B.5.6	E-mail	ghulam.mufti@kcl.ac.uk
B.Sponsor: 2
B.1.1	Name of Sponsor	King's College London
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	King's College Hospital NHS Foundation Trust
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	King's College London
B.5.2	Functional name of contact point	Professor Ghulam Mufti
B.5.3	Address:
B.5.3.1	Street Address	Denmark Hill
B.5.3.2	Town/ city	London
B.5.3.3	Post code	SE5 9RS
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	004402032993080
B.5.5	Fax number	004402073463514
B.5.6	E-mail	ghulam.mufti@kcl.ac.uk

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Revlimid
D.2.1.1.2	Name of the Marketing Authorisation holder	Celgene Europe Limited
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/04/192
D.3 Description of the IMP
D.3.1	Product name	Revlimid®
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	LENALIDOMIDE
D.3.9.1	CAS number	191732-72-6
D.3.9.3	Other descriptive name	Revlimid
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Myelodysplastic Syndrome (MDS) associated with a Del (5q) cytogenetic abnormality

E.1.1.1

Medical condition in easily understood language

MDS is a disease of the bone marrow, in which the production of blood cells slows down considerably. This syndrome carries a risk of developing leukaemia.

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.0
E.1.2	Level	LLT
E.1.2	Classification code	10067097
E.1.2	Term	5q minus MDS
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

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%

E.2.2

Secondary objectives of the trial

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

E.2.3

Trial contains a sub-study

E.3

Principal 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.
• All subjects must
o Agree to abstain from donating blood while taking study drug therapy and for 28 days following discontinuation of study drug therapy.
8. Laboratory test results within these ranges:
• Absolute neutrophil count > 0.5 x 109/L
• Platelet count > 25 x 109/L
• Serum creatinine < 2.0 mg/dl
• Total bilirubin < 1.5 mg/dl
• AST (SGOT) and ALT (SGPT) < 3 x ULN.
9. Disease free of prior malignancies for > 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma “in-situ” of the cervix or breast.
10. Agree not to share study drug with another person and to return all unused study drug to the investigator or pharmacist

E.4

Principal 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.

E.5 End points

E.5.1

Primary end point(s)

Red blood cell (RBC) transfusion independence.

E.5.1.1

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

E.5.2

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.

E.5.2.1

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

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

Last visit of last subject

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Upon discontinuation of treatment with IMP, patients' care will return as per standard clinical practice. Patients will be followed up three monthly as part of survival contact.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2005-02-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2005-01-12

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-05-23

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