Clinical Trials Register

Summary
EudraCT Number:	2010-022584-35
Sponsor's Protocol Code Number:	TUD-BRIDGE-046
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-09-28
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

Germany - BfArM

A.2

EudraCT number

2010-022584-35

A.3

Full title of the trial

Clofarabine salvage therapy in patients with relapsed or refractory AML
The BRIDGE Trial

(Therapie mit Clofarabin bei rezidivierter oder refraktärer akuter myeloischer Leukämie (Bridge-Studie))

A.3.1

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

Clofarabine therapy in patients with relapsed or refractory acute myeloid leukemia

A.4.1

Sponsor's protocol code number

TUD-BRIDGE-046

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	Dresden Universtity of Technology
B.1.3.4	Country	Germany
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	Penn Pharmaceutical Services (Penn)
B.4.2	Country	United Kingdom
B.4.1	Name of organisation providing support	Genzyme Clinical Pharmacy Research Services
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Universitätsklinikum Dresden, Med. Klinik und Poliklinik I
B.5.2	Functional name of contact point	Head of Clinical Trials Unit
B.5.3	Address:
B.5.3.1	Street Address	Fetscherstraße 74
B.5.3.2	Town/ city	Dresden
B.5.3.3	Post code	01307
B.5.3.4	Country	Germany
B.5.4	Telephone number	+49351458-03775
B.5.5	Fax number	+49351458-04367
B.5.6	E-mail	christoph.roellig@uniklinikum-dresden.de

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
D.2.1.1.2	Name of the Marketing Authorisation holder	Genzyme
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
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	Evoltra
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
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

Patients with AML >40 years of age with untreated relapse or refractory disease after a minimum of one standard
induction therapy.

E.1.1.1

Medical condition in easily understood language

Patients with relapsed or refractory acute myeloid leukemia

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10060557
E.1.2	Term	Acute myelocytic leukemia
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

To study the safety and efficacy of clofarabine salvage therapy prior to allogeneic HCT. (Rate of treatment success)

E.2.2

Secondary objectives of the trial

- rate of treatment success by risk group
- rate of HCT
- rate of adverse drug reactions
- cause-specific treatment failure

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

(1) Diagnosis of AML according to WHO criteria.
(2) Untreated relapse or refractory disease after a minimum of one standard induction therapy. Treatment of
relapse with leukocyte-apheresis or up to 5 days with low dose cytarabine or hydroxyurea is allowed.
• Refractory disease is defined as ≥5% blasts after the second cycle of induction therapy or no reduction in
marrow blasts at early treatment assessment (day +15) after the first cycle of induction therapy.
• Relapse is defined as an increase in bone marrow blast count ≥5%, re-appearance of blasts in the peripheral
blood or extramedullary disease.
(3) Age above 40 years.
(4) Have adequate renal and hepatic functions as indicated by the following laboratory values:
• Serum creatinine ≤1.0 mg/dL; if serum creatinine >1.0 mg/dL, then the estimated glomerular filtration rate
(GFR) must be >60 mL/min/1.73 m2 (see reference below*)
• Serum bilirubin ≤1.5× upper limit of normal (ULN)
• Aspartate transaminase (AST)/alanine transaminase (ALT) ≤2.5× ULN
• Alkaline phosphatase ≤2.5× ULN
(5) Eligibility for intensive chemotherapy
(6) Patient needs to be capable to understand the clinical trial as an investigational approach to bridge the time to
potential allogeneic HCT, potential risks and benefits of the study.
(7) Signed written informed consent.
(8) Female patients of childbearing potential must have a negative serum pregnancy test within 3 days prior to
enrollment.
(9) Male and female patients must use an effective contraceptive method during the study and for a minimum of 6
months after study treatment.

* Calculation of Creatinine Clearance by the Modification of Diet in Renal Disease equation where Predicted
GFR (ml/min/1.73 m2) = 186x (Serum Creatinine)-1.154 x (age in years)-0.023 x (0.742 if patient is female) x
(1.212 if patient is black).

E.4

Principal exclusion criteria

(1) For refractory disease, more than two prior induction chemotherapies or more than one prior salvage
chemotherapy containing high-dose cytarabine (cumulative dose of cytarabine ≥ 5 g/m2).
(2) Second or higher relapse. Patients who received hypomethylating agents like azacytidine or decitabine as a
treatment of first relapse, respond and relapse later on may be included.
(3) Acute promyelocytic leukemia with t(15;17)(q22;q12) molecular detection or (PML/RARα).
(4) Central nervous system involvement (i.e. WBC ≥ 5/μL in cerebrospinal fluid with blasts present on cytospin).
(5) Prior allogeneic HCT
(6) Autologous transplantation within 100 days prior to start of study treatment
(7) Use of investigational agents or anticancer therapy within 10 days before study entry with the exception of
hydroxyurea or low-dose cytarabine.
(8) 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 transplantation.
(9) Patients with known refractoriness to platelet support.
(10) Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting
ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or
other treatment).
(11) Pregnant or lactating patients.
(12) Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or
compliance, interfere with consent, study participation, follow up, or interpretation of study results.

E.5 End points

E.5.1

Primary end point(s)

Rate of treatment success (Treatment success is defined as complete remission after salvage therapy with clofarabine only or after bridging therapy with clofarabine together with conditioning prior to allogeneic HCT.)

E.5.1.1

Timepoint(s) of evaluation of this end point

after completion of study treatment

E.5.2

Secondary end point(s)

Rate of treatment success by risk group, rate of HCT, rate of adverse drug reactions, cause-specific treatment failure

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

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

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

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

LVLS - provided in the 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 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)

provided in the 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

2010-11-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-11-25

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-08-23

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