Clinical Trials Register

Summary
EudraCT Number:	2022-000557-88
Sponsor's Protocol Code Number:	Anti-CD19-ALL
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:	2022-06-30
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

2022-000557-88

A.3

Full title of the trial

A Prospective Phase I/II, Single-Arm, Open-Label, Multicentre Study to Evaluate the Safety and Efficacy of Tafasitamab (MOR00208) in Pediatric Patients with Relapsed or Refractory Acute B Lineage Leukemia

Durchführung einer multizentrischen, prospektiven Phase I/II Studie zur Überprüfung der Sicherheit und der Wirksamkeit von Tafasitamab (MOR00208) bei pädiatrischen Patienten mit Rückfall einer akuten B-Zell Leukämie bzw. Behandlungs-refraktärer akuter B-Zell Leukämie

A.3.1

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

Tafasitamab against childhood leukemia

Tafasitamab gegen Leukämie im Kindesalter

A.3.2

Name or abbreviated title of the trial where available

Anti-CD19-ALL

A.4.1

Sponsor's protocol code number

Anti-CD19-ALL

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT05366218

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	University Hospital Tuebingen
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	Incyte Biosciences International Sàrl
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Center for Pediatric Clinical Studies
B.5.2	Functional name of contact point	CPCS
B.5.3	Address:
B.5.3.1	Street Address	Frondsbergstr. 23
B.5.3.2	Town/ city	Tuebingen
B.5.3.3	Post code	72070
B.5.3.4	Country	Germany
B.5.4	Telephone number	004970712981469
B.5.5	Fax number	00497071294857
B.5.6	E-mail	cd19-studie@med.uni-tuebingen.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	Tafasitamab
D.2.1.1.2	Name of the Marketing Authorisation holder	Incyte Biosciences
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Tafasitamab
D.3.2	Product code	MOR00208
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.3.11 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)	Yes
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

B-lineage (CD19 positive) ALL (B, pro-B, pre-B or c-ALL) refractory to standard treatment or with relapsed disease

E.1.1.1

Medical condition in easily understood language

Leukemia in childhood

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	10024338
E.1.2	Term	Leukemia lymphoblastic acute
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Part I: To determine the recommended dose of MOR00208 in pediatric patients on the basis of the maximum tolerated dose (MTD).
Part II: To evaluate the time until hematological relapse (> 5% leukemic blasts) or increase of MRD ≥ 2 log in bone marrow during an observation time of 545 days accounting for competing risks.

E.2.2

Secondary objectives of the trial

Part I:
1. To evaluate the pharmacokinetics with measurement of plasma concentrations of MOR00208
2. Assessment of Safety of MOR00208 by NCI Common Toxicity Criteria, version 5.0.
Part II:
1. To determine the rate of patients with "Success of treatment", defined as survival without newly emerging MRD or increasing MRD ≥ 2 log in bone marrow or peripheral blood or unacceptable toxicity/infections.
2. To evaluate the overall survival.
3. To evaluate changes in minimal residual disease during and after treatment in bone marrow aspirates with evaluation of the rate of patients with MRD reduction of at least 1 log at any time point compared to baseline.
4. To evaluate changes in peripheral B cell numbers by flow cytometry in peripheral blood until the end of follow-up.
5. To evaluate the cytotoxicity of patient derived PBMCs against cell lines (NALM) and cryopreserved autologous blasts.
6. Assessment of Safety of MOR00208 by NCI Common Toxicity Criteria, version 5.0.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Age < 18 years at enrollment
o only children ≥ 3 years at enrollment will be enrolled prior to the identification of the recommended Phase II dose (maximum tolerated dose, MTD)
• B-lineage (CD19 positive) ALL (B, pro-B, pre-B or c-ALL)
• Patients must have either underwent a first allogeneic stem cell transplantation with newly emerging or persistent MRD load posttransplant or have received stem cell transplantation without having reached a sufficient molecular remission prior to transplant (defined as MRD ≥10E-4) irrespective of MRD after SCT or underwent a second or subsequent allogeneic stem cell transplantation irrespective of MRD after SCT
• Informed consent must be given by patients or legal representatives

E.4

Principal exclusion criteria

• Frank relapse (>5% leukemic blasts)
• Philadelphia chromosome-positive (Ph+) ALL
• Ejection fraction <25% on echocardiography
• Cystatin C-clearance <40ml/min
• Liver function abnormalities with bilirubin >4 mg/dL and elevation of transaminases higher than 400 U/L
• Severe infection (HIV, Chronic active viral hepatitis), tests have to be conducted at screening
• Acute GvHD III-IV or extensive chronic GvHD
• The following immunosuppressive drugs (≥ 1 week of administration): steroids ≥ 1mg/kg body weight, cytostatics (except intrathecal/intracerebroventricular application for CNS treatment)
• Application of other experimental therapy modalities in the last 4 weeks
• Significant psychiatric disabilities, uncontrolled seizure disorders or severe peripheral neuropathy/ leukencephalopathy
• Signs of autoimmune disease (i.e. idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia)
• Subjects that do not agree to refrain from donating blood while on study drug
• Concurrent severe or uncontrolled medical disease which by assessment of the treating physician could compromise participation in the study
• Women during pregnancy and lactation
• History of hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product.

E.5 End points

E.5.1

Primary end point(s)

1. Recommended dose of MOR00208 in pediatric patients, determined on the basis of the maximum tolerated dose (MTD)
2. Time until hematological relapse (> 5% leukemic blasts) or increase of MRD ≥ 2 log in bone marrow during an observation time of 545 days accounting for competing risks.

E.5.1.1

Timepoint(s) of evaluation of this end point

1. End of Part I.
2. Day 545.

E.5.2

Secondary end point(s)

- Pharmacokinetic of MOR00208
- Safety and toxicity of MOR00208
- Rate of patients with treatment success defined as survival without newly emerging MRD or increasing MRD ≥ 2 log in bone marrow or peripheral blood or unacceptable toxicity.
- Overall survival.
- Rate of patients with MRD reduction of at least 1 log at any time point compared to basline MRD measurement between SCT and start of study treatment.
- B cell numbers at several time points.
- Cytotoxicity of patient derived PBMCs against cell lines (NALM) and cryopreserved autologous blasts at several time points.
- Safety and toxicity of MOR00208
Safety endpoints:
• Any toxicity irrespective of grade
• Number of Deaths
• Number of Relapses
• Adverse events will be presented in line listings and also in cumulative tabulations.

E.5.2.1

Timepoint(s) of evaluation of this end point

Day 365 for the rate of patients with treatment success. Day 545 for the other endpoints.

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

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

First in pediatric patients.

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.8.6 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

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

The end of the study is defined as the completion of the trial report.

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

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:

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)

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

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)

Patients will be carefully monitored according to the centers policy. In general, 1-2 visits per year will be carried out until 10 years after allogeneic stem cell transplantation. Clinical status and remission status will be assessed.

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

2022-11-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-11-14

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

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