Clinical Trials Register

Summary
EudraCT Number:	2010-022946-25
Sponsor's Protocol Code Number:	AALL0622
Clinical Trial Type:	Outside EU/EEA
Date on which this record was first entered in the EudraCT database:	2011-12-19
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
H.4 THIRD COUNTRY IN WHICH THE TRIAL WAS FIRST AUTHORISED

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A. Protocol Information

A.2

EudraCT number

2010-022946-25

A.3

Full title of the trial

Intensified Tyrosine Kinase Inhibitor Therapy (Dasatinib: IND# 73969, NSC# 732517) in Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (ALL)

A.3.1

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

Dasatinib and Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

A.4.1

Sponsor's protocol code number

AALL0622

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT00720109

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/200/2011

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Children's Oncology Group
B.1.3.4	Country	United States
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	Children's Oncology Group
B.4.2	Country	United States
B.4.1	Name of organisation providing support	National Cancer Institute
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	The Children’s Hospital of Philadelphia
B.5.2	Functional name of contact point	Peter C. Adamson - COG Group Chair
B.5.3	Address:
B.5.3.1	Street Address	3501 Civic Center Blvd, CTRB 10060
B.5.3.2	Town/ city	Philadelphia
B.5.3.3	Post code	PA 19104
B.5.3.4	Country	United States
B.5.4	Telephone number	1(215) 590-6359
B.5.5	Fax number	1(215) 590-7544
B.5.6	E-mail	Adamson@email.chop.edu

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/3/05/338-339
D.3 Description of the IMP
D.3.1	Product name	Dasatinib
D.3.2	Product code	BMS-354825
D.3.4	Pharmaceutical form	Film-coated tablet
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	DASATINIB
D.3.9.1	CAS number	302962-49-8
D.3.9.2	Current sponsor code	BMS-354825
D.3.9.4	EV Substance Code	SUB23322
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	20
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.IMP: 2
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/3/05/338-339
D.3 Description of the IMP
D.3.1	Product name	Dasatinib
D.3.2	Product code	BMS-354825
D.3.4	Pharmaceutical form	Film-coated tablet
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	DASATINIB
D.3.9.1	CAS number	302962-49-8
D.3.9.2	Current sponsor code	BMS-354825
D.3.9.4	EV Substance Code	SUB23322
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.IMP: 3
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/3/05/338-339
D.3 Description of the IMP
D.3.1	Product name	Dasatinib
D.3.2	Product code	BMS-354825
D.3.4	Pharmaceutical form	Film-coated tablet
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	DASATINIB
D.3.9.1	CAS number	302962-49-8
D.3.9.2	Current sponsor code	BMS-354825
D.3.9.4	EV Substance Code	SUB23322
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	50
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

Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (ALL)

E.1.1.1

Medical condition in easily understood language

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	10000844
E.1.2	Term	Acute lymphoblastic leukaemia
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

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	10034877
E.1.2	Term	Philadelphia chromosome positive
E.1.2	System Organ Class	10022891 - Investigations

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 determine the feasibility and toxicity of dasatinib in combination with intensified chemotherapy in young patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia.
•To determine whether the intensification of tyrosine kinase inhibition (TKI) through the addition of dasatinib to induction therapy (on days 15-28) and the substitution of dasatinib for imatinib mesylate during post-induction therapy will lead to a 3-year event-free survival (EFS) in ≥ 60% of these patients.

E.2.2

Secondary objectives of the trial

•To determine whether the addition of dasatinib to induction therapy will decrease levels of minimal residual disease (MRD) present at the end of induction therapy as compared with MRD levels in patients treated on COG-AALL0031.
•To determine whether early intensified TKI therapy (dasatinib) will lower levels of MRD at the end of consolidation therapy as compared with MRD levels in patients who received imatinib mesylate during blocks 1 and 2 consolidation therapy (cohorts 3-5) on COG-AALL0031.
•To determine the overall 3-year EFS rate for both standard- and high-risk patients treated with dasatinib.
•To determine the long-term effects of dasatinib on growth, development, and bone metabolism.
•To assess BCR-ABL mutation status at time of diagnosis and progression/relapse.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

DISEASE CHARACTERISTICS:
•Newly diagnosed acute lymphoblastic leukemia (ALL)
◦Definitive evidence of BCR-ABL fusion (Philadelphia chromosome positive [PH+]) from an approved Children's Oncology Group (COG) cytogenetics laboratory
•Meets one of the following criteria:
◦Concurrent enrollment on COG-AALL03B1 (or a successor trial) AND COG-AALL0232, COG-AALL0331, COG-AALL0434 or other front-line COG ALL clinical trial
◦Concurrent enrollment on COG-AALL03B1 (or a successor trial) AND scheduled to receive a 3 or 4-drug standard induction regimen
◦Concurrent enrollment on a DFCI Childhood ALL Consortium trial (or scheduled to be treated as per a DFCI Childhood ALL Consortium induction regimen)
•Received the first 2 weeks of induction therapy prior to study enrollment
◦Patients may NOT have received day 15 of induction therapy (or day 18 if enrolled on a DFCI Childhood ALL Consortium trial)
•No Down syndrome
PATIENT CHARACTERISTICS:
•Karnofsky performance status (PS) 50-100% (for patients > 16 years of age)
•Lansky PS 50-100% (for patients ≤ 16 years of age)
•Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR maximum serum creatinine based on age and gender as follows:
◦0.4 mg/dL (for patients 1 to 5 months of age)
◦0.5 mg/dL (for patients 6 to 11 months of age)
◦0.6 mg/dL (for patients 1 year of age)
◦0.8 mg/dL (for patients 2 to 5 years of age)
◦1.0 mg/dL (for patients 6 to 9 years of age)
◦1.2 mg/dL (for patients 10 to 12 years of age)
◦1.5 mg/dL (males) or 1.4 mg/dL (females) (for patients 13 to 15 years of age)
◦1.7 mg/dL (males) or 1.4 mg/dL (females) (for patients ≥ 16 years of age)
•Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
•ALT < 2.5 times ULN
•Shortening fraction ≥ 27% by echocardiogram OR LVEF ≥ 50% by gated radionuclide study
•QTc ≤ 0.45 seconds by EKG
•Not pregnant or nursing
•Negative pregnancy test
•Fertile patients must use effective contraception
•No evidence of dyspnea at rest
•No exercise intolerance
•Pulse oximetry > 94% at sea level (if there is a clinical indication for determination)
•Seizure disorder allowed provided it is well controlled on anticonvulsants
PRIOR CONCURRENT THERAPY:
•No other concurrent cancer chemotherapy or immunomodulatory agents (including steroids)

E.4

Principal exclusion criteria

• Females of childbearing potential must have a negative pregnancy test. Patients of childbearing potential must agree to use an effective birth control method.
• Female patients who are lactating must agree to stop breast-feeding.
• Patients with Down syndrome
• Patients with QTc greater than 0.45 seconds. Patients must have an EKG fewer than 6 days prior to enrollment onto AALL0622.

E.5 End points

E.5.1

Primary end point(s)

•Feasibility as assessed by examining the adverse events, delays in administering combination therapy, minimal residual disease (MRD) levels at the completion of induction therapy and consolidation therapy, and event-free survival (EFS)
•Toxicity as assessed by NCI CTCAE v3.0
•3-year event-free survival (EFS) of patients with standard-risk disease treated with dasatinib in combination with intensified chemotherapy

E.5.1.1

Timepoint(s) of evaluation of this end point

•At the end-of-induction - Day 28
•At the end-of-consolidation block 2
•Overall 3-year EFS rate

E.5.2

Secondary end point(s)

•Comparison of the end-of-induction minimal residual disease (MRD) levels in patients treated with dasatinib on this study with the end-of-induction MRD levels in patients treated on clinical trial COG-AALL0031
•Comparison of the end-of-consolidation MRD levels in patients treated with dasatinib on this study with the end-of-consolidation MRD levels in patients treated with imatinib mesylate during blocks 1 and 2 consolidation therapy (cohorts 3-5) on COG
•Overall 3-year EFS rate for both standard- and high-risk patients

E.5.2.1

Timepoint(s) of evaluation of this end point

•At the end-of-induction - Day 28
•At the end-of-consolidation block 2
•Overall 3-year EFS rate

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)

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

E.8.1.1

Randomised

E.8.1.2

Open

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

Will this trial be conducted at a single site globally?

E.8.4

Will this trial be conducted at multiple sites globally?

Yes

E.8.6 Trial involving sites outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Yes

E.8.6.3

Specify the countries outside of the EEA in which trial sites are planned

Australia

Canada

New Zealand

Puerto Rico

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

Last Patient Last Visit

E.8.9 Initial estimate of the duration of the trial

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

Yes

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)

Yes

F.1.1.4.1

Number of subjects for this age range:

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

114

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

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)

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

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Chldren from 1 to 30 years old

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.2

For a multinational trial

F.4.2.2

In the whole clinical trial

195

G. Investigator Networks to be involved in the Trial

H.4 Third Country in which the Trial was first authorised
H.4.1	Third Country in which the trial was first authorised:	United States

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