Clinical Trials Register

Summary
EudraCT Number:	2010-018965-42
Sponsor's Protocol Code Number:	CC-4047-MF-002
National Competent Authority:	Sweden - MPA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-01-07
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

Sweden - MPA

A.2

EudraCT number

2010-018965-42

A.3

Full title of the trial

A PHASE-3, MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP STUDY TO COMPARE EFFICACY AND SAFETY OF POMALIDOMIDE IN SUBJECTS WITH MYELOPROLIFERATIVE NEOPLASM -ASSOCIATED MYELOFIBROSIS AND RED BLOOD CELL-TRANSFUSION-DEPENDENCE

A.3.1

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

Study to compare the safety and efficacy of pomalidomide versus a non-active pill in patients who need frequent red blood cell transfusions due to bone marrow scaring (fibrosis) associated with specific bone marrow disorders (MPNs – polycythemia vera, essential thrombocythemia, and primary myelofib.rosis)

A.3.2

Name or abbreviated title of the trial where available

RESUME

A.4.1

Sponsor's protocol code number

CC-4047-MF-002

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01178281

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	Celgene Corporation
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Celgene Corporation
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Celgene Corporation
B.5.2	Functional name of contact point	ClinicalTrialDisclosure
B.5.3	Address:
B.5.3.1	Street Address	9225 Indian Creek Parkway, Suite 900
B.5.3.2	Town/ city	Kansas
B.5.3.3	Post code	66210
B.5.3.4	Country	United States
B.5.4	Telephone number	+1-888-260-1599
B.5.5	Fax number	+1 913-266-0394
B.5.6	E-mail	ClinicalTrialDisclosure@celgene.com

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	No
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/3/10/757
D.3 Description of the IMP
D.3.1	Product name	Pomalidomide
D.3.2	Product code	CC-4047
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	Pomalidomide
D.3.9.1	CAS number	19171-19-8
D.3.9.2	Current sponsor code	CC-4047
D.3.9.3	Other descriptive name	NA
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	0.5
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule, hard
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Myeloproliferative Neoplasm (MPN) Associated Myelofibrosis defined as primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (post-PV MF) and post-essential thrombocythemia myelofibrosis (post-ET MF)

E.1.1.1

Medical condition in easily understood language

Cancer of the bone marrow where normal blood cell growth is affected and collagen fibers begin to develop in the marrow

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	14.1
E.1.2	Level	PT
E.1.2	Classification code	10028537
E.1.2	Term	Myelofibrosis
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

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

Compare efficacy of pomalidomide versus placebo in achieving Red Blood Cell (RBC)-transfusion-independence in subjects with Myeloproliferative neoplasm-associated myelofibrosis with RBC-transfusion-dependence.

E.2.2

Secondary objectives of the trial

Evaluate safety of pomalidomide in subjects with MPN-associated myelofibrosis with RBC-transfusion-dependence.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Age ≥18 years of age at the time of signing the informed consent document.

2. MPN-associated myelofibrosis (primary myelofibrosis (PMF), post-polycythemia vera
myelofibrosis (post-PV MF) and/or post-essential thrombocythemia myelofibrosis (post-ET MF)

3. RBC-transfusion-dependence:
- Average RBC-transfusion frequency of ≥2 U/28 days over at least the 84 days
immediately prior to randomization. There must be no interval >42 days without
≥1 RBC-transfusion.
- Only RBC-transfusions given when the hemoglobin ≤90 g/L^3 are scored in
determining eligibility.
- RBC-transfusions due to bleeding are not scored in determining eligibility
- RBC-transfusions due to chemotherapy-induced anemia are not scored in
determining eligibility.

4. Hemoglobin ≤130 g/L at randomization.

5. Bone marrow slides that meet defined criteria for central histological review will be
submitted to a central reviewer.

6. A blood cell or bone marrow allo-transplant should not be an appropriate therapy at this time.

7. Erythropoietin should not be an appropriate therapy at this time.

8. Androgenic steroids should not be an appropriate therapy at this time.

9. Treatment with systemic corticosteroids is permitted for non-hematological conditions providing the subject is receiving a stable or decreasing dose for ≥84 days immediately prior to randomization and are receiving a constant dose equivalent to ≤10 mg prednisone for the 28 days immediately prior to randomization.

10. Eastern Cooperative Oncology Group (ECOG) performance score ≤2.

11. Females of childbearing potential (FCBP) must undergo pregnancy testing based on the frequency outlined in protocol Appendix 18.1 and pregnancy results must be negative.

12. Unless practicing complete abstinence from heterosexual intercourse, sexually active FCBP must agree to use adequate contraceptive methods as specified in protocol Appendix 18.1.

13. Males (including those who have had a vasectomy) must use barrier contraception (condoms) when engaging in sexual activity with FCBP as specified in Appendix 18.1.

14. Males must agree not to donate semen or sperm during the duration specified in Appendix 18.1.

15. 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
- Agree not to share study medication with another person.
- Be counseled about pregnancy precautions and risks of fetal exposure.

16. Understand and voluntarily sign an informed consent document before any study related assessments/procedures are conducted.

17. Able to adhere to the study visit schedule and other protocol requirements.

E.4

Principal exclusion criteria

The presence of any of the following will exclude a subject from enrollment:
1. Prior bone marrow or blood cell transplant.

2. Use of drugs to treat MPN-associated myelofibrosis ≤30 days pre-randomization(42 days for hydroxyurea) or ongoing adverse events from previous treatment.

3. Use of an erythropoietin or androgenic steroids ≤84 days pre- randomization.

4. Anemia from other proved causes other than MPN-associated myelofibrosis.

5. Pregnant or lactating females.

6. More than 10% blasts by bone marrow examination or more than 10% blasts in blood in consecutive measurements spanning at least 8 weeks.

7. Prior history of malignancies, other than the disease being studied, unless the subject has been free of the malignancy for ≥ 5 years with the following exceptions:
-Basal cell carcinoma of the skin,
-Squamous cell carcinoma of the skin
-Carcinoma in situ of the cervix
-Carcinoma in situ of the breast
-Incidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system)

8. Proved human immunodeficiency virus-1 (HIV-1) infection

9. Active hepatitis B virus (HBV) or active hepatitis C Virus (HCV) infection.

10. Prior therapy with pomalidomide.

11. Any of the following adverse reactions to prior therapy with thalidomide or lenalidomide:
- Prior ≥grade-2 National Cancer Institute (NCI) Common Terminology Criteria
for Adverse Events (CTCAE) allergic reaction to thalidomide and/or lenalidomide
- Prior desquamating (blistering) rash while taking thalidomide and/or lenalidomide
- Hypersensitivity to thalidomide and lenalidomide

12. Any of the following laboratory abnormalities:
-Neutrophils <0.5x10e9/L
- Platelets <25 x 10e9/L
- Estimated glomerular filtration rate <30 mL/min/1.73m2
- Aspartate aminotransferase (AST),and alanine transaminase (ALT) >3.0 x upper limit of normal (ULN)
- Total bilirubin ≥4 x ULN;
- Uncontrolled hyperthyroidism or hypothyroidism.

13. Deep venous thrombosis (DVT) or pulmonary embolus (PE) <6 months pre-randomization.

14. Heart disease ≤6 months pre-randomization including:
- New York Heart Association class >II, congestive heart failure
- Unstable angina
- Myocardial infarction within 6 months

15. Any significant medical condition, laboratory abnormality or psychiatric illness that
would prevent the subject from participating in the study.

16. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.

17. Any condition that confounds the ability to interpret data from the study.

E.5 End points

E.5.1

Primary end point(s)

Proportion of subjects achieving ≥ 84 consecutive days of RBC-transfusion-independence

E.5.1.1

Timepoint(s) of evaluation of this end point

At the end of study week 24 (Day 169) then, every 28 days until relapse or discontinuation for any reason.
Group analysis: when the last subject randomized reaches Day 169 evaluation

E.5.2

Secondary end point(s)

1) Duration of RBC-transfusion-independence
2) Time to becoming RBC-transfusion-independent
3) Survival - alive or dead
4) Frequency of AE's
5) Healthcare resource utilization
6) EQ-5D Health Outcome Assessment
7) FACT-An Quality of Life (QoL) Assessment

E.5.2.1

Timepoint(s) of evaluation of this end point

1) Every 28d until relapse/discontinuation for any reason; 2) Every 28d until all responders are identified; 3) Every 4months during the first 2 years following treatment discontinuation, then every 6 months until 5 years after subject was randomized; 4) & 5) every 28d until 28d after subject’s final dose of study medication; 6) At Day 1, 85, 169 and at treatment discontinuation; 7) At D1, D84 and every 84d while on treatment and at treatment discontinuation

1st analysis of all endpoints: when all subjects have completed the blinded treatment phase. 2nd analysis: 2 years after the last subject was randomized. 3rd analysis: 5 years after the last subject was randomized

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

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

Yes

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

QoL (EQ-5D, FACT-An)

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

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

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Canada

China

Japan

Russian Federation

United States

E.8.7

Trial has a data monitoring committee

Yes

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

At the end of the follow up phase, minimum 5 years after the last subject is randomized in the study, or until the last subject dies.

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

Number of subjects for this age range:

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:

115

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

137

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.4.2

For a multinational trial

F.4.2.1

In the EEA

123

F.4.2.2

In the whole clinical trial

252

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)

See protocol

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

2011-02-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-02-09

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2018-05-15

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