VEN-DEC GITMO Study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Gruppo Italiano Per Il Trapianto Di Midollo Osseo Cellule Staminali Emopoietiche E Terapia Cellulare

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

13 May 2021 → 31 Jan 2026

Decision date (initial)

2024-12-16

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Janssen · Abbvie

External identifiers

EU CT number

2024-518792-54-00

EudraCT number

2020-002297-26

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

The primary objective of the study is to evaluate the proportion of elderly (≥60 - <75 years) patients with newly diagnosed AML eligible for allo-SCT treated with the “chemo-free” combination Venetoclax plus Decitabine (VEN-DEC) who get allo-SCT in CR, CRi or MLFS.

Secondary objectives 1

1. Incidence and severity of adverse drug reactions (ADR) classified by System Organ Class (SOC) and preferred term (PT) from start treatment with Ventoclax and Decitabine to allo-SCT - Efficacy of VEN-DEC combination - Evaluation of the outcome of allo-SCT in term of: 1) Incidence of graft failure at day +30, +100 from allo-SCT 2) Incidence of Non-Relapse Mortality (NRM) at day +100, 1 year and 2 years from allo-SCT 3) Incidence and severity of acute GVHD at day +100 from allo-SCT 4) Incidence and severity of chronic GVHD at 1 year and 2 years from allo-SCT 5) Probability of GRFS (GVHD free, relapse free survival) at 1 and 2 years from allo-SCT - Relapse incidence (RI) at 1 year and 2 years from allo-SCT - Disease-free survival (DFS) at 1 and 2 years from allo-SCT - Overall Survival (OS) at 1 and 2 years from allo-SCT - Correlation of immunophenothype, cytogenetic, molecular and NGS-genomic profiles with sensitivity (CR/CRi/MLFS) or resistance (PR/NR) to “chemo-free” combination Venetoclax plus Decitabine (VENDEC) - Correlation of immunophenothype, cytogenetic, molecular and NGS-genomic profiles with the outcome of allo-SCT in terms of NRM, probability of RI, DFS, OS.

Conditions and MedDRA coding

Acute Myeloid Leukemia (AML)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. • Patients ≥ 60 <75 years of age • Diagnosis of AML eligible for allo-SCT from any donor • High- and Intermediate-Risk ELN • WBC <25x109/L (Hydroxyurea is permitted to meet this criterion) • Adequate hepatic function (bilirubin ≤2 UNL; ALT/AST ≤2,5 UNL) • Adequate renal function (creatinine clearance ≥50 ml/min) • ECOG Performance Status ≤ 2 • Males enrolled in the study with partners who are women of childbearing potential, must be willing to use an acceptable barrier contraceptive method during the trial. • Women of childbearing potential must use highly effective contraception for at least 1 month after the last dose of VEN and for however long the EU SmPC says for DEC • Willing and able to comply with all of the requirements and visits in the protocol. • Written and signed informed consent.

Exclusion criteria 1

1. • Previous treatment for AML (Hydroxyurea is allowed) or for an antecedent Myelodysplastic Syndrome (MDS) • Subject has known active CNS involvement with AML • Absence of informed consent • AML patients with t(15;17); t(8;21); inv(16) • Low Risk ELN grade > 2 NCI-CTCAE (v. 5) adverse events at the time of enrollment • Serious organ dysfunction: left ventricular ejection fraction < 40%, FEV1, FVC, DLCO (diffusion capacity) < 40% of predicted, LFT > 5 times the upper limit of normal, or creatinine clearance < 40 ml/min. • The evidence of HBV or HCV active infection (HBV DNA HCV RNA positive test). • Patients with HIV infection • Current uncontrolled infections • Patients with other life-threatening concurrent disease • Patients receiving strong CYP3A inducers (eg Carbamazepime, Phenytoin, Rifampicin), within seven days before the first dose of VEN-DEC combination. • Subjects with known hypersensitivity to any of the component medication • Subject has a history of other malignancies within 2 years prior to study entry, with the exception of: - Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast; - Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; - Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent. • Participation in another clinical trial within 1 month before the start of this trial.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of elderly (≥60 - <75 years) patients with newly diagnosed AML eligible for allo-SCT treated with the “chemo-free” combination Venetoclax plus Decitabine (VEN-DEC) who get allo-SCT in CR/CRi/MLFS.

Secondary endpoints 1

1. - Efficacy of VEN-DEC combination - Cumulative incidence of graft failure at +30 days, +100 days from transplant - Outcome of allo-SCT in term of NRM at day +100, 1 year and 2 years from allo-SCT - Cumulative incidence and severity of acute GvHD at 100 days after transplant - Cumulative incidence and severity of chronic GvHD at 1 and 2 years post transplant - RI at 1 and 2 year after transplantation from days of transplant. - OS at 1 and 2 years post transplant - DFS at 1 and 2 years post

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Gruppo Italiano Per Il Trapianto Di Midollo Osseo Cellule Staminali Emopoietiche E Terapia Cellulare

Sponsor organisation

Gruppo Italiano Per Il Trapianto Di Midollo Osseo Cellule Staminali Emopoietiche E Terapia Cellulare

Address

Via De' Poeti 1/7

City

Bologna

Postcode

40124

Country

Italy

Scientific contact point

Organisation

Gruppo Italiano Per Il Trapianto Di Midollo Osseo Cellule Staminali Emopoietiche E Terapia Cellulare

Contact name

Eliana Degrandi

Public contact point

Organisation

Gruppo Italiano Per Il Trapianto Di Midollo Osseo Cellule Staminali Emopoietiche E Terapia Cellulare

Contact name

Francesca Monari

Third parties 2

Locations

1 EU/EEA country · 7 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 7 files

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

Application history

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