Clinical Trials Register

Summary
EudraCT Number:	2019-003863-23
Sponsor's Protocol Code Number:	TUD-MOSAIC-075
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2019-11-28
Trial 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 - PEI

A.2

EudraCT number

2019-003863-23

A.3

Full title of the trial

Midostaurin + Gemtuzumab Ozogamicin combination in first-line standard therapy for acute myeloid leukemia

Midostaurin in Kombination mit Gemtuzumab Ozogamicin als Erstlinientherapie für Patienten mit akuter myeloischer Leukämie

A.3.1

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

Addition of midostaurin and gemtuzumab ozogamicin to standard chemotherapy with cytarabine and daunorubicin in patients with newly diagnosed acute myeloid leukemia

A.3.2

Name or abbreviated title of the trial where available

MOSAIC

A.4.1

Sponsor's protocol code number

TUD-MOSAIC-075

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	Technische Universität Dresden
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	Novartis Pharma GmbH
B.4.2	Country	Germany
B.4.1	Name of organisation providing support	Pfizer Pharma GmbH
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Medizinische Fakultät Carl Gustav Carus der TU Dresden, Medizinische Klinik und Poliklinik I
B.5.2	Functional name of contact point	Coordinating Investigator
B.5.3	Address:
B.5.3.1	Street Address	Fetscherstr. 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	00493514583775
B.5.5	Fax number	00493514584367
B.5.6	E-mail	MOSAIC@ukdd.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	Rydapt
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Ltd
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/3/04/214
D.3 Description of the IMP
D.3.1	Product name	Rydapt
D.3.4	Pharmaceutical form	Capsule, soft
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	MIDOSTAURIN
D.3.9.1	CAS number	120685-11-2
D.3.9.3	Other descriptive name	MIDOSTAURIN
D.3.9.4	EV Substance Code	SUB21040
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	25
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	Yes
D.2.1.1.1	Trade name	Mylotarg
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer Europe MA EEIG
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/3/00/005
D.3 Description of the IMP
D.3.1	Product name	Mylotarg
D.3.4	Pharmaceutical form	Powder for 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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	GEMTUZUMAB OZOGAMICIN
D.3.9.1	CAS number	220578-59-6
D.3.9.4	EV Substance Code	SUB20794
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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 newly diagnosed acute myeloid leukemia (AML) fit for intensive curative treatment displaying a cytogenetic aberration or fusion transcript in the core-binding factor (CBF) genes or FLT3 mutation

E.1.1.1

Medical condition in easily understood language

Patients with newly diagnosed acute myeloid leukemia (AML) fit for intensive curative treatment displaying anomalies in target genes CBF and FLT3

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	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10000886
E.1.2	Term	Acute myeloid 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

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the tolerability and efficacy of midostaurin plus gemtuzumab ozogamicin (GO) in combination with standard AML induction chemotherapy

E.2.2

Secondary objectives of the trial

To investigate potential correlations between CD33 expression, c-kit expression, FLT3-ITD mutational load and response

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

− Written informed consent
− Newly diagnosed AML according to WHO criteria plus the following molecular or cytogenetic specifications:
o Phase I (Dose escalation):
• t(8;21)/RUNX1-RUNX1T1 or
• inv(16) or t(16;16)/CBFB-MYH11 or
• FLT3-ITD or
• FLT3-TKD
o Phase II (MAGNOLIA) Expansion in CBF AML
• t(8;21)/RUNX1-RUNX1T1 or
• inv(16) or t(16;16)/CBFB-MYH11,
o Phase II (MAGMA) Expansion in FLT3mut AML
• FLT3-ITD or
• FLT3-TKD
• Absence of mutations in the core-binding factor genes (i.e. t(8;21)/RUNX1-RUNX1T1 or inv(16) or t(16;16)/CBFB-MYH11)
− Male and female patients with age
• 18-70 years
− ECOG 0-2,
− Life expectancy > 14 days,
− Adequate hepatic and renal function
• ALAT/ASAT ≤ 2.5 x ULN
• Bilirubin < 2 x ULN
• Creatinin < 1.5 x ULN or Creatinine clearance > 40 ml/min,
− White blood cell count < 30 × 10^9/L. Note: Hydroxyurea and/or a dose of 100-200 mg/m^2 cytarabine per day for up to 3 days (for emergency use
for clinical stabilization) is permitted to meet this criterion.

E.4

Principal exclusion criteria

− Previous antineoplastic treatment for AML other than hydroxyurea and/or cytarabine for emergency use (100-200 mg/m^2 per day on maximal 3 days),
− Previous treatment with anthracyclines,
− CNS involvement,
− Uncontrolled infection,
− Strong CYP3A4/5 enzyme inducing drugs unless they can be discontinued or replaced prior to enrollment.

E.5 End points

E.5.1

Primary end point(s)

- Phase I (Dose escalation): Maximum tolerated dose of midostaurin plus gemtuzumab ozogamicin in combination with standard induction chemotherapy within a 3+3 design
- Phase II (Expansion): Event-free survival

E.5.1.1

Timepoint(s) of evaluation of this end point

Phase I: day 28-42 of induction cycle 1 = DLT Evaluation period
Phase II: up to 3 years from enrolment (unless the event occurs earlier)

E.5.2

Secondary end point(s)

− CR/CRi rate,
− Depth of remission and measurable residual disease (MRD) by PCR-based RUNX1-RUNX1T1 or CBFB-MYH11 and NPM1 measurements and by multicolor flow cytometry (MFC),
− Duration of remission, cumulative incidence of relapse,
− Relapse-free survival,
− Overall survival,
− Early mortality (ED30, ED60),
− Tolerability (toxicity, adverse events, VOD),
− CD33 expression of AML blasts,
− Proportion of allogeneic stem cell transplantation following response.

E.5.2.1

Timepoint(s) of evaluation of this end point

up to 3 years from enrolment

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)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

to investigate the combination of midostaurin and gemtuzumab ozogamicin with standard induction

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

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

the control group receives standard of care treatment

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

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 Patient last visit

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

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:

214

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

214

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

214

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)

Information is 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

2020-03-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-07-03

P. End of Trial
P.	End of Trial Status	Ongoing

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