Phase III Clinical Trial for CPX-351 in Myeloid Leukemia in Children with Down Syndrome 2018

Overview

Sponsor-declared trial summary

Key facts

Sponsor

GPOH gGmbH

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

28 Oct 2024 → ongoing

Decision date (initial)

2023-08-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2022-501457-37-00

EudraCT number

2018-002988-25

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Therapy, Safety, Efficacy

Achieving an EFS, which is not inferior to the ML-DS 2006 trial: 5yr-EFS; 87±3%

Secondary objectives 4

1. Reduction of toxicity: severe adverse events (CTCAE v4.0 grade III or higher)
2. Identification of prognostic factors (e.g. trisomy 8) concerning the risk of relapse, toxicity and poor outcome
3. To evaluate the role of different methods in the determination of minimal residual disease measurement
4. To evaluate the response rate

Conditions and MedDRA coding

Myeloid Leukemia in Children with Down Syndrome

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Trisomy 21: Down syndrome or mosaic
2. Age: > 6 months and ≤ 4 years of age with/without GATA1 mutation OR > 4 years of age < 6 years of age with GATA1 mutation
3. Morphology/Immunophenotyping: FAB M0, M6 or M7
4. Lansky performance score at least equal to 50; or Karnofsky performance status at least equal to 50, whichever is applicable
5. Understand and voluntarily provide written permission of parental/legal representative(s) to the ICF prior to conducting any study related assessments/procedures, also concerning data and tumor material transfer according to ICH/GCP and national/local regulations
6. Able to adhere to the study visit schedule and other protocol requirements
7. Acceptance that vaccination with live vaccines is not possible while participating in the trial
8. Myeloid Leukemia (ML) or Myelodysplastic Syndrome (MDS), according to WHO

Exclusion criteria 13

1. Children with Transient Abnormal Myelopoiesis (TAM), according to WHO
2. Cytogenetics: AML with recurrent genetic abnormalities (WHO 2016)
3. Previous allogeneic bone marrow, stem cell or organ transplantation
4. Evidence of invasive fungal infection or other severe systemic infection requiring treatment doses of systemic/parenteral therapy including known active viral infection with human immunodeficiency virus (HIV) or Hepatitis Type B and C
5. Symptomatic cardiac disorders (CTCAE 4.0 Grade 3 or 4)
6. Diagnosed Wilson's Disease
7. Major surgery within 21 days of the first dose
8. Any anti-cancer therapy (e.g., intensive chemotherapy, biologics or radiotherapy) for more than 14 days or within 4 weeks before start of therapy, except low-dose cytarabine for the treatment of TAM
9. Concomitant treatment with any other anticancer therapy except those specified in protocol during the study therapy
10. Treated by any investigational agent in a clinical study within previous 4 weeks
11. 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
12. Former Enrolment to this study
13. The patient concerned has been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Event-free survival (EFS), defined as time from diagnosis to the first event or last follow-up. Events are death from any cause, failure to achieve remission, relapse, and secondary malignancy. Failure to achieve remission is considered as an event on day 0.

Secondary endpoints 7

1. Overall survival (OS), as defined as the time of diagnosis to death from any cause or last follow-up
2. Disease-free survival (DFS)
3. Early Response Rate (CR, CRp, CRi) after induction
4. Treatment-related mortality (TRM)
5. Minimal residual disease (FACS and NGS)
6. Adverse events (according to NCI CTCAE v4.0)
7. Duration of myelosuppression (neutrophils <0.5 Gpt/L)

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

GPOH gGmbH

Sponsor organisation

GPOH gGmbH

Address

Holsterhauser Platz 2, Holsterhausen Holsterhausen

City

Essen

Postcode

45147

Country

Germany

Scientific contact point

Organisation

GPOH gGmbH

Contact name

Prof. Dr. med Jan-Henning Klusmann

Public contact point

Organisation

GPOH gGmbH

Contact name

Prof. Dr. med Dirk Reinhardt

Third parties 2

Locations

7 EU/EEA countries · 93 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 5 · Art. 38 CTR

Results and documents

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

Documents 32 files

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

Application history

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