VyClo ITCC-092

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Prinses Maxima Centrum voor Kinderoncologie B.V.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

17 Jul 2025 → ongoing

Decision date (initial)

2024-03-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Jazz Pharmaceuticals

External identifiers

EU CT number

2023-508050-26-00

EudraCT number

2020-000142-34

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy, Pharmacokinetic

To establish the recommended phase 2 dose of Vyxeos®/CPX-351 in combination with clofarabine in children with relapsed/refractory AML.

Secondary objectives 1

1. • To determine the safety and tolerability of this combination • To determine the (preliminary) efficacy in terms of the hematological remission rate in these patients as determined by morphology with flow cytometric confirmation. • To describe the durability of response, including the number of patients that undergo stem- cell transplant after re-induction with this regimen

Conditions and MedDRA coding

AML

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. Any ≥ 2nd relapse of AML • Refractory AML (defined as ≥ 20% blasts in the bone marrow after standard (re-) induction therapy) • Early 1st relapse (defined as relapse within one year from initial diagnosis) of AML • Any relapse of AML after prior allogenic HSCT • Any relapse of AML with high risk cytogenetic characteristics • Complete initial work-up within 7 days prior to study entry, including bone-marrow aspiration, lumbar puncture (without intrathecal therapy) • Lansky play score ≥ 60 for patients <16 years of age; or Karnofsky performance status ≥ 60 for patients ≥ 16 years of age • Life expectancy > 6 weeks • a calculated GFR ≥ 70mL/min/1.73 m2 • Liver function: total serum bilirubin ≤ 3 mg/dl or 50 µmol/L and aspartate transaminase (AST) and alanine transaminase (ALT) ≤200 U/L • Adequate cardiac function (defined as shortening fraction ≥28% or ejection fraction ≥50%)

Exclusion criteria 1

1. evidence of a currently uncontrolled bacterial, viral or parasitic infection • evidence of a fungal infection, defined as either: - Pulmonary infiltrates suggestive of a fungal infection at HR-CT (within 3 weeks prior to enrollment) - Positive Aspergillus serum test (galactomannan), according to local laboratory practice (within 3 weeks prior to enrollment) • evidence of isolated extramedullary relapse, including isolated CNS-relapse • evidence of CNS3 or symptomatic CNS leukemia • Down Syndrome • evidence of relapsed/refractory acute promyelocytic leukemia (APL) • use of any anticancer therapy within 2 weeks before study entry. The patient must have recovered from all acute toxicities from any previous therapy (note: hematological toxicities do not need to be considered since the patient has overt leukemia) • history of prior veno-occlusive disease (VOD) • known hypersensitivity to cytarabine, clofarabine or liposomal daunorubicin • known copper metabolism deficiency, such as Wilson's disease.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Frequency of Dose-limiting toxicities (DLTs) during the first course of therapy

Secondary endpoints 1

1. 1. Safety and tolerability: frequency of AEs, frequency of clinically significant laboratory abnormalities and number of toxic deaths 2. Measures of anti-leukemic activity3. Overall patient survival and relapse-free survival 4. Number of patients undergoing HSCT after treatment. 5. Serum and intracellular pharmacokinetic parameters 6. Relationship between response (ORR) and Ara-CTP accumulation 7.Correlation between duration of response and measurable residual disease assessed by flow-cytometry

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Prinses Maxima Centrum voor Kinderoncologie B.V.

Sponsor organisation

Prinses Maxima Centrum voor Kinderoncologie B.V.

Address

Heidelberglaan 25

City

Utrecht

Postcode

3584 CS

Country

Netherlands

Scientific contact point

Organisation

Prinses Maxima Centrum voor Kinderoncologie B.V.

Contact name

[email protected]

Public contact point

Organisation

Prinses Maxima Centrum voor Kinderoncologie B.V.

Contact name

[email protected]

Third parties 1

Locations

6 EU/EEA countries · 13 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 6 · Art. 38 CTR

Application history

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