Comparison of therapies before stem cell transplantation in patients with higher risk MDS and oligoblastic AML

Overview

Sponsor-declared trial summary

Key facts

Sponsor

GWT-Tud GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

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

Trial duration

26 Aug 2019 → ongoing

Decision date (initial)

2024-10-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Jazz Pharmaceutical Inc.

External identifiers

EU CT number

2024-515375-35-00

EudraCT number

2018-002430-21

WHO UTN

U1111-1311-4059

ClinicalTrials.gov

NCT04061239

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

To compare event-free survival (EFS) of CPX-351 vs. CCR before allogeneic blood cell transplantation (alloHCT) as first line treatment in patients with higher risk MDS and oligoblastic AML.

Secondary objectives 6

1. To compare best and overall response of CPX-351 vs. CCR
2. To compare the safety and tolerability of CPX-351 vs. CCR
3. To compare the effects of CPX-351 vs. CCR on the proportion of patients proceeding to alloHCT
4. To compare the effect of CPX-351 vs. CCR on minimal residual disease (MRD)
5. To compare the effect of CPX-351 vs. CCR on quality of life
6. Key secondary objective: To compare OS of CPX-351 vs. CCR

Conditions and MedDRA coding

Untreated patients with higher risk MDS and oligoblastic AML eligible and intended for allogeneic HCT within the next 6 months

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Adult patients (irrespective of sex), 18-75 years of age
2. Diagnosis of high risk MDS including oligoblastic non-proliferative (WBC <13 Gpt/l) AML up to 29% of bone marrow blasts
3. Bone marrow blasts ≥ 5% (central morphology Düsseldorf)
4. IPSS score intermediate or high
5. alloHCT intended within the next 6 months
6. ECOG performance status of 0 or 1
7. Signed informed consent
8. Laboratory values fulfilling all of the following: Serum creatinine < 2.0 mg/dL; Serum total bilirubin < 2.0 mg/dL; Serum alanine aminotransferase or aspartate aminotransferase < 3 times the ULN
9. Cardiac ejection fraction (LVEF) ≥ 50% by echocardiography
10. Contraception: - Female subjects of childbearing potential† must agree to use a medically acceptable method of contraception for at least 2 months prior to the first dose of CPX-351 and consent of female patients to use a medically acceptable method of contraception throughout the entire study period and for 6 months following the last dose of CPX-351; Male patients must be willing to refrain from sperm donation for 6 months following the last dose of CPX-351 and must use adequate contraception throughout the entire study period and for 6 months following the last dose of CPX-351

Exclusion criteria 15

1. Patients with history of myeloproliferative neoplasms (MPN) (defined as a history of essential thrombocytosis or polycythemia vera, or idiopathic myelofibrosis prior to the diagnosis of AML) or combined MDS/MPN are not eligible.
2. WHO-2016 defined AML entities: AML with t(15;17), PMLRARA; AML with t(8;21), RUNX1-RUNX1T1, AML with inv(16)/t(16;16), CBFβ-MYH11; AML with BCR-ABL1, AML with biallelic CEBPA mutation; AML with mutated FLT3 or NPM1.
3. Clinical evidence of active CNS leukaemia.
4. Patients with a “currently active” second malignancy other than non-melanoma skin cancers. Patients are not considered to have a “currently active” malignancy if they have completed therapy more than 2 years ago and are disease free.
5. Any major surgery or radiation therapy within four weeks prior screening.
6. Patients with prior treatment of either CPX-351, hypomethylating agents, cytarabine or intensive chemotherapy for high-risk MDS or AML.
7. Patients with prior cumulative anthracycline exposure of greater than 368 mg/m2 daunorubicin (or equivalent).
8. Recent (< 30 days) or planned live vaccinations during the clinical trial.
9. Any serious medical condition, laboratory abnormality or psychiatric illness that would prevent obtaining informed consent.
10. Creatinine clearance < 30 ml/min.
11. Active or uncontrolled infection. Patients with an infection receiving treatment (antibiotic, antifungal or antiviral treatment) may be entered into the study but must be afebrile and hemodynamically stable for ≥ 72 hrs.
12. Current evidence of invasive fungal infection (blood or tissue culture); patients with recent fungal infection must have a subsequent negative cultures to be eligible; known HIV (new testing not required) or evidence of active hepatitis B or C infection (with rising transaminase values).
13. Hypersensitivity to cytarabine, daunorubicin or liposomal products.
14. History of Wilson’s disease or other copper-metabolism disorder, unless the therapy outweighs the risks.
15. Female patients who are pregnant or lactating.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. EFS with a data cut off date of September 2025

Secondary endpoints 6

1. Best and overall response rate according to AML-ELN and MDS-IWG criteria
2. Toxicity as measured by NCI CTCAE v5.0
3. Proportion of patients proceeding to alloHCT
4. MRD assessed at all times of BM puncture
5. Quality of life as measured by EORTC-QLQ30 supplemented by information on self-assessed concomitant diseases and demographics upon inclusion and at EOT (i.e. before alloHCT, if applicable)
6. Key Secondary Endpoint: OS with a data cut-off dates of September 2025 for interim and September 2026 for final

Investigational products

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

Test 1

Comparator 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

GWT-Tud GmbH

Sponsor organisation

GWT-Tud GmbH

Address

Freiberger Strasse 33, Wilsdruffer Vorstadt/seevorstadt-West Wilsdruffer Vorstadt/seevorstadt-West

City

Dresden

Postcode

01067

Country

Germany

Scientific contact point

Organisation

GWT-Tud GmbH

Contact name

Fachbereich MEDIZIN

Public contact point

Organisation

GWT-Tud GmbH

Contact name

Fachbereich MEDIZIN

Third parties 6

Locations

2 EU/EEA countries · 26 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 22 files

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

Application history

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