Clinical Trials Register

Summary
EudraCT Number:	2008-001043-19
Sponsor's Protocol Code Number:	CLO-34100405
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2008-08-22
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

France - ANSM

A.2

EudraCT number

2008-001043-19

A.3

Full title of the trial

Phase III Randomized, Double-Blind, Controlled Study Comparing Clofarabine and Cytarabine versus Cytarabine Alone in Adult Patients 55 Years and Older with Acute Myelogenous Leukemia (AML) who have Relapsed or are Refractory after Receiving up to Two Prior Induction Regimens

A.3.2

Name or abbreviated title of the trial where available

CLASSIC I

A.4.1

Sponsor's protocol code number

CLO-34100405

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Genzyme Europe BV
B.1.3.4	Country	Netherlands
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	Evoltra 1 mg/ml concentrate for solution for infusion
D.2.1.1.2	Name of the Marketing Authorisation holder	Genzyme Europe BV
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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/3/03/141
D.3 Description of the IMP
D.3.1	Product name	Clofarabine
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CLOFARABINE
D.3.9.1	CAS number	123318-82-1
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Cytarabine
D.2.1.2	Country which granted the Marketing Authorisation	France
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	CYTARABINE
D.3.4	Pharmaceutical form	Powder for infusion*
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CYTARABINE
D.3.9.1	CAS number	147-94-4
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	500
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Acute Myelogenous (Myeloid) Leukemia (AML)

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10000880
E.1.2	Term	Acute myeloid leukaemia

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 assess the efficacy of clofarabine in combination with cytarabine compared with cytarabine alone in adult patients 55 years and older with AML who have either relapsed or are refractory after receiving up to two prior induction regimens, as measured by overall survival.

E.2.2

Secondary objectives of the trial

• To determine the overall remission (OR) rate (CR + CRi) of clofarabine in combination with cytarabine compared with cytarabine alone;
• To determine the duration of remission and disease-free survival for each treatment group;
• To compare treatment groups with respect to event-free survival and 4-month event-free survival;
• To determine the safety and tolerability of clofarabine when used in combination with cytarabine compared with cytarabine alone and the duration, seriousness, severity and relationship of adverse events which occur during the treatment and follow-up period, including hospitalizations.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients must meet all of the following criteria to be eligible to participate in the study:
(1) Provide signed, written informed consent.
(2) Have a diagnosis of AML according to the WHO classification (see Appendix B of the study protocol).
(3) Have received not more than 2 prior induction regimens for treatment of AML according to the following definitions and qualifications:
• Induction regimen: a drug or combination of drugs administered for a pre-specified number of cycles (usually not exceeding 2 cycles total) to patients with AML with the intent of achieving a CR or CRi;
• At least 1 prior induction regimen must have included cytotoxic chemotherapy;
• Hematopoietic stem cell transplantation (HSCT) (administered after induction therapy) is not considered a distinct induction regimen.
• Consolidation or maintenance regimens (administered after CR or CRi documented) are not considered distinct induction regimens.
(4) Are refractory or relapsed (requiring at least 5% leukemic blasts in the bone marrow, regardless of the presence of other features such as new or recurrent dysplastic changes or extramedullary disease).
(5) Be 55 years of age or older at the time of signing the informed consent.
(6) Have an ECOG performance status (see Appendix C) score of 0, 1, or 2.
(7) Be able to comply with study procedures and follow-up examinations.
(8) Be nonfertile or agree to use birth control (ie, condom, diaphragm, cervical cap, etc) during the study and for at least 90 days after the last dose of study drug.
(9) Have adequate renal and hepatic function as indicated by the following
laboratory values:
Renal-Estimated GFR : ≥60 mL/min/1.73m2
Hepatic-
Serum bilirubin: ≤1.5 × ULN
AST and ALT: ≤2.5 × ULN
Alkaline phosphatase: ≤2.5 × ULN
GFR = Glomerular filtration rate, as estimated by the Modification of Diet
in Renal Disease (MDRD) equation (see appendix E)
ULN = Institutional Upper Limit of Normal

E.4

Principal exclusion criteria

((1) Received previous treatment with clofarabine.
(2) Received intermediate- or high-dose cytarabine (IDAC or HDAC, respectively) defined as a bolus administration schedule at ≥500 mg/m2/dose as a component of prior induction or consolidation therapy.
(3) Have received an HSCT within the previous 3 months prior to study entry.
(4) Have ≥ grade 2 acute graft versus host disease (GvHD).
(5) Have either moderate or severe chronic GvHD, whether limited or extensive chronic GvHD. Patients with mild limited or extensive chronic GvHD may be included.
(6) Are receiving any other systemic antileukemic therapy (standard or investigational). Patients must not have received previous therapy for at least 2 weeks prior to the first dose of study drug and must have recovered from any prior drug-related non-hematologic toxicity to ≤ grade 2, with the following exceptions:
• hydroxyurea, which must not have been received <24 hours prior to the first dose of study drug;
• monoclonal antibodies, which must not have been received for 6 weeks prior to the first dose of study drug.
(7) Have psychiatric disorders that would interfere with consent, study participation, or follow-up.
(8) Have a systemic fungal, bacterial, viral, or other infection not controlled.
(9) Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver or other organ system that may place the patient at undue risk to undergo induction therapy with either or both of these agents.
(10) Have been diagnosed with another malignancy, unless the patient has been
disease free for at least 5 years following curative intent therapy.
(11) Have clinical evidence suggestive of CNS involvement with leukemia unless a lumbar puncture confirms the absence of leukemic blasts in the CSF.
(12) Known HIV positivity
(13) Are pregnant or lactating.

E.5 End points

E.5.1

Primary end point(s)

Overall survival

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

Information not present in EudraCT

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)

Yes

E.8.2.2

Placebo

Yes

E.8.2.3

Other

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

Information not present in EudraCT

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

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

See protocol

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 months

F. Population of Trial Subjects
F.1 Age Range
F.1.1	Trial has subjects under 18	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	12
F.4.2	For a multinational trial
F.4.2.1	In the EEA	36
F.4.2.2	In the whole clinical trial	376

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

2008-10-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2008-11-03

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2010-05-25

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