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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitaetsklinikum Tuebingen AöR

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

11 Aug 2023 → ongoing

Decision date (initial)

2024-08-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Incyte Biosciences International Sàrl, Switzerland

External identifiers

EU CT number

2024-511336-28-00

EudraCT number

2022-000557-88

ClinicalTrials.gov

NCT05366218

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Pharmacokinetic, Efficacy

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.

Secondary objectives 6

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. To evaluate the pharmacokinetics with measurement of plasma concentrations of MOR00208 pre-dose, end-of-infusion, 1h post-dose, 24h post-dose and pre-next-dose at MOR00208 infusion No. 1 and 7.

Conditions and MedDRA coding

Leukemia in childhood

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Age >=3 to <18 years
2. B-lineage (CD19 positive) ALL (B, pro-B, pre-B or c-ALL)
3. Refractory to standard treatment or with relapsed disease
4. • Patients must have either underwent a first allogeneic stem cell transplantation after relapse with one of the following very high-risk somatic molecular alterations - KMT2A::AFF1 [t(4;11) rearrangement, TP53 alteration (mutation/deletion), low hypodiploidy (<40 chromosomes, evident or masked), TCF3-PBX1 [t(1;19)], TCF3::HLF [t(17;19)] - and irrespective of MRD after SCT or underwent a first allogeneic stem cell transplantation or a CAR T-cell therapy with newly emerging or persistent MRD load posttransplant / post CAR T-cell-treatment 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
5. Informed consent must be given by patients or legal representatives

Exclusion criteria 14

1. Frank relapse (>5% leukemic blasts)
2. Ejection fraction <25% on echocardiography
3. Cystatin C-clearance <40ml/min
4. Liver function abnormalities with bilirubin >4 mg/dL and elevation of transaminases higher than 400 U/L
5. Severe infection (HIV, Chronic active viral hepatitis), tests have to be conducted at screening
6. Acute GvHD III-IV or extensive chronic GvHD
7. The following immunosuppressive drugs (≥ 1 week of administration): steroids ≥ 1mg/kg body weight, cytostatics (except intrathecal/intracerebroventricular application for CNS treatment)
8. Application of other experimental therapy modalities in the last 4 weeks
9. Significant psychiatric disabilities, uncontrolled seizure disorders or severe peripheral neuropathy/ leukencephalopathy
10. Signs of autoimmune disease (i.e. idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia)
11. Subjects that do not agree to refrain from donating blood while on study drug
12. Concurrent severe or uncontrolled medical disease which by assessment of the treating physician could compromise participation in the study
13. Women during pregnancy and lactation
14. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 9

1. 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.
2. Overall survival.
3. 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
4. Cytotoxicity of patient derived PBMCs against cell lines (NALM) and cryopreserved autologous blasts at several time points.
5. Pharmacokinetic of MOR00208.
6. Safety endpoint: Any toxicity irrespective of grade
7. Safety endpoint: Number of Deaths
8. Safety endpoint: Number of relapses
9. Safety endpoint: Adverse events will be presented in line listings and also in cumulative tabulations.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaetsklinikum Tuebingen AöR

Sponsor organisation

Universitaetsklinikum Tuebingen AöR

Address

Geissweg 3, Innenstadt Innenstadt

City

Tübingen

Postcode

72076

Country

Germany

Scientific contact point

Organisation

Universitaetsklinikum Tuebingen AöR

Contact name

Center for Pediatric Clinical Studies

Public contact point

Organisation

Universitaetsklinikum Tuebingen AöR

Contact name

Center for Pediatric Clinical Studies

Locations

1 EU/EEA country · 12 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications