Clinical Trials Register

Summary
EudraCT Number:	2018-002619-89
Sponsor's Protocol Code Number:	B1761031
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2018-12-27
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 - PEI

A.2

EudraCT number

2018-002619-89

A.3

Full title of the trial

A SINGLE ARM, OPEN-LABEL, PHASE 4 STUDY EVALUATING QT INTERVAL,
PHARMACOKINETICS, AND SAFETY OF GEMTUZUMAB OZOGAMICIN
(MYLOTARG™) AS A SINGLE-AGENT REGIMEN IN PATIENTS WITH
RELAPSED OR REFRACTORY CD33-POSITIVE ACUTE MYELOID LEUKEMIA

A.3.1

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

A Phase 4 study evaluating the effect of GO (MYLOTARG™) on the QTc,
pharmacokinetics, safety, and immunogenicity of GO as a single-agent therapy in patients with relapsed or refractory blood cancer.

A.4.1

Sponsor's protocol code number

B1761031

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	Pfizer Inc., 235 East 42nd Street, New York, NY 10017
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	Pfizer, Inc.
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	Pfizer Inc.
B.5.2	Functional name of contact point	Clinical Trials.gov Call Center
B.5.3	Address:
B.5.3.1	Street Address	235 East 42nd Street
B.5.3.2	Town/ city	New York, NY
B.5.3.3	Post code	10017
B.5.3.4	Country	United States
B.5.4	Telephone number	1 8007181021
B.5.6	E-mail	ClinicalTrials.gov_Inquiries@pfizer.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	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 (EMEA/OD/022/00)
D.3 Description of the IMP
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.3.9.2	Current sponsor code	PF-05208747
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	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)	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

relapsed or refractory CD33-positive acute myeloid leukaemia (AML)

E.1.1.1

Medical condition in easily understood language

acute myeloid leukaemia (AML) a cancer of the blood

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	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10000886
E.1.2	Term	Acute myeloid leukemia
E.1.2	System Organ Class	100000004864

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 effect of GO on the QTc interval

E.2.2

Secondary objectives of the trial

To characterize the PK of single-agent GO following the fractionated
regimen (ie, 3 mg/m² on Days 1, 4, and 7).
- To assess the safety of GO with fractionated dosing of 3 mg/m2.
- To assess the immunogenicity of GO.
- To assess response and overall survival.

Exploratory Objectives:
- To assess CD33 saturation and relation to the fractionated regimen of GO.
- To assess CD33 expression by central lab immunophenotyping.
- To assess metabolites after treatment with GO.
- To collect banked biospecimens for exploratory research, unless prohibited by local regulations or ethics committee decision.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Refractory or relapsed (ie, bone marrow blasts ≥5%) CD33-positive AML.
2. Age≥12 years.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2.
4. Initial peripheral white blood cells (WBC) counts <30,000/ μL;
patients with a higher WBC count should undergo cytoreduction.
5. Adequate renal/hepatic functions, ie:
- Serum creatinine ≤1.5 x upper limit of normal (ULN) or any serum
creatinine level associated with a measured or calculated creatinine
clearance of ≥40 mL/min;
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
<2.5×ULN; total bilirubin <2×ULN.
6. Negative serum or urine pregnancy (human chorionic gonadotropin
[hCG]) test within 1 week before treatment for women of child bearing
potential.
7. Evidence of a personally signed and dated informed consent document
and obtaining proper pediatric assent in addition to consent according to
local regulations (by the caregivers or legally acceptable representative
[eg, parents] in the pediatric patients) indicating that the patient [or a legally acceptable representative/parent(s)/legal guardian] has been informed of all pertinent aspects of the study.
8. Willing and able to comply with scheduled visits, treatment plan,
laboratory tests, and other study procedures.
9. Female patients of non-childbearing potential must meet at least 1 of
the following criteria:
- Achieved postmenopausal status, defined as follows: cessation of
regular menses for at least 12 consecutive months with no alternative
pathological or physiological cause; status may be confirmed with a serum follicle-stimulating hormone (FSH) level confirming the postmenopausal state;
- Have undergone a documented hysterectomy and/or bilateral oophorectomy;
- Have medically confirmed ovarian failure.
All other female patients (including female patients with tubal ligations) are considered to be of childbearing potential.

E.4

Principal exclusion criteria

1. Patients with prior treatment with GO.
2. Patients with prior history of VOD/SOS.
3. Prior HSCT is not allowed, if it was conducted within 2 months prior to
study enrollment.
4. Patients with known active central nervous system (CNS) leukemia.
5. Uncontrolled or active infectious status.
6. Any of the following within the 3 months prior to starting study
treatment: myocardial infarction, severe/unstable angina,
coronary/peripheral artery bypass graft, congestive heart failure, or
cerebrovascular accident including transient ischemic attack, or
symptomatic pulmonary embolism.
7. Uncontrolled cardiac dysrhythmias of NCI CTCAE Grade 2,
uncontrolled atrial fibrillation of any grade.
8. Sero-positivity to human immunodeficieny virus (HIV).
9. Active hepatitis B or hepatitis C infection (see Appendix 2 of the protocol).
10. Chemotherapy, radiotherapy, or other anti-cancer therapy (except
hydroxyurea as cytoreduction) within 2 weeks prior to enrollment in the
study.
11. Major surgery within 4 weeks prior to enrollment.
12. Diagnosis of any other malignancy within 3 years prior to enrollment,
except for adequately treated basal cell or squamous cell skin cancer, or
carcinoma in situ of the cervix.
13. QTc interval >470 milliseconds (msec) using the Fridericia (QTcF)
(based on the mean value of the triplicate electrocardiograms [ECGs]),
family or personal history of long or short QT syndrome, Brugada
syndrome or known history of QTc prolongation, or Torsade de Pointes
(TdP).
14. The use of medications known to predispose to Torsades de Pointes
within 2 weeks prior to enrollment (see Appendix 4 of the protocol).
15. History of allergic reactions attributed to compounds of similar
chemical or biologic composition to GO.
16. Investigator site staff members directly involved in the conduct of
the study and their family members, site staff members otherwise
supervised by the investigator, or patients who are Pfizer employees,
including their family members, directly involved in the conduct of the
study.
17. Participation in other studies involving investigational drug(s) within
2 weeks prior to study entry and/or during study participation.
18. Other acute or chronic medical or psychiatric condition including
recent (within the past year) or active suicidal ideation or behavior or
laboratory abnormality that may increase the risk associated with study
participation or investigational product administration or may interfere
with the interpretation of study results and, in the judgment of the
investigator, would make the patient inappropriate for entry into this
study.
19. Pregnant female patients; breastfeeding female patients; fertile male
patients and female patients of childbearing potential who are unwilling
or unable to use 2 highly effective methods of contraception as outlined
in this protocol for the duration of the study and for 7 months after the
last dose of investigational product.

E.5 End points

E.5.1

Primary end point(s)

Maximum change from baseline in corrected QT interval (QTc).

E.5.1.1

Timepoint(s) of evaluation of this end point

Triplicate ECGs will be performed at screening, baseline (prior to dose on Day 1) and on each day of dosing (Days 1, 4, and 7 of at cycle). ECGs will be paired with PK blood sampling and collected immediately prior to the PK blood sample collection, such that the blood sample is collected at the nominal planned time. Additional ECGs will be performed as clinically indicated for patient safety monitoring and documentation stored in the source documents.

All ECGs will be sent to the ECG core laboratory for independent reading and interpretation.
Additional information on timepoints collection is provided in the Schedule of activities Table 2 (page 16) and Assessment of Primary Endpoints (section 7.1.1).

E.5.2

Secondary end point(s)

- PK parameters: clearance and volume of distribution.
- Adverse events (AEs) and abnormal laboratory findings.
- Incidence of anti-drug antibody (ADA)/neutralizing antibodies (NAb).
- Response: complete remission (CR) and complete remission with incomplete hematologic recovery (CRi) achieved after GO.
- Overall Survival.

Exploratory endpoints:
- CD33 site saturation levels in peripheral blood (PB) in relation to GO.
- CD33 expression in bone marrow or peripheral blood.
- Metabolic profiling in plasma and urine.
- Collection of banked biospecimens unless prohibited by local regulations or ethics committee decision. Additional information on collection and potential use is provided in the Banked Biospecimens section.

E.5.2.1

Timepoint(s) of evaluation of this end point

- Samplings for PK will be collected at several days and times during Cycle 1 (Day 1: H0, H1, H2, H4, H6 and H24; Day 4: H0 and H2; Day 7: H0, H2, H4 and H6; Day 10; Day 15 and D21) and during Cycle 2 (Day 1: H0, H2; Day 7: H0, H2, H6; Day 15; Day 21; End of Treatment (EoT)).
- Samplings for ADA/Nab will be collected at baseline, at Day 15 and Day 21 of each cycle and at EoT.
- Efficacy evaluation and determination of remission status by blood and bone marrow aspiration (and biopsy if applicable) will be conducted at the end of each cycle.

Additional information on timepoints collection is provided in the Schedule of activities Table 2 (page 16) and Assessment of secondary Endpoints (sections 7.2, 7.3, 7.4, 7.5 and 7.6).

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

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

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)

E.7.4

Therapeutic use (Phase IV)

Yes

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

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

Canada

Germany

Hungary

Poland

Spain

United Kingdom

United States

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

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

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)

F.1.1.5

Children (2-11years)

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)

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

6 Paediatric Patients Aged 12-17 will be enrolled in the study.

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

F.4.2.2

In the whole clinical trial

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)

No difference from the normal treatment of this condition.

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

2019-01-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-06-05

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-07-22

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