PENTALLO (PENTAglobin in Acute Leukemia and ALLOgeneic transplants)

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

28 Jan 2025 → ongoing

Decision date (initial)

2025-01-28

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

BIOTEST

External identifiers

EU CT number

2024-518940-19-02

EudraCT number

2018-001344-57

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To demonstrate that the early addition of Pentaglobin to the best available antimicrobial therapy is able to reduce mortality and improve survival in neutropenic febrile acute leukemia or allo- Hematopoietic stem cell transplantation (HSCT) patients colonized by carbapenem-resistant Enterobacteriaceae (CRE) or by any Pseudomonas aeruginosa (PA).

Secondary objectives 1

1. To evaluate the overall impact of Pentaglobin administration in the study population concerning: adverse drug reactions, infectious complications and treatment-related mortality. Incidence and severity of acute and chronic GvHD. Incidence of graft failure / time to neutrophil and platelet recovery. Probability of GRFS (GvHD free, relapse free survival).

Conditions and MedDRA coding

Acute Myeloid Leukemia (AML)

Regulatory references

Plan to share IPD

Yes

IPD plan description

Individual participant data are collected on the electronic CRF. The Redcap platform Is used for CRF and each PI of each Center has credentials for accessing. The IPD sharing statement Is included in the informed consent.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Age > or = 18 years
2. Performance status: ECOG <3
3. Diagnosis of acute myeloid leukemia or acute lymphoblastic leukemia candidate to intensive chemotherapy or Indication to allogeneic Hematopoietic stem cell transplantation (HSCT) for hematological cancers, including severe aplastic anemia (second transplants allowed)
4. Pre-treatment colonization by Carbapenem-resistant Enterobacteriaceae (CRE) or Pseudomonas aeruginosa (PA) documented by rectal and/or pharyngeal swab or pre-treatment bloodstream infection sustained by CRE or PA
5. Written and signed informed consent
6. Patients participating in other clinical studies for allogeneic HSCT are also eligible to this study if the above-mentioned trials are using an approved investigational compound
7. Possibility of starting treatment with Pentaglobin <12 hours after development of fever
8. Treatment with other immunoglobulins (e.g. IVIG, Cytotect) should be not administered during the time of treatment with Pentaglobin.
9. Women of child-bearing potential enrolled in the study must have a negative pregnancy test at screening and agree to use two distinct acceptable methods of contraception during the trial.
10. Men enrolled in the study with partners who are women of child bearing potential, must be willing to use an acceptable barrier contraceptive method during the trial.

Exclusion criteria 6

1. Uncontrolled systemic infection
2. Hypersensitivity to the active substance or to any of the excipients of Pentaglobin
3. Patients with previous anaphylaxis or severe reactions to immunoglobulins preparation
4. Severe concomitant illness: o patients with severe renal impairment o patients with severe pulmonary impairment o patients with severe cardiac impairment o patients with severe hepatic impairment
5. Patients who on the basis of the investigator's consideration are not able to give the informed consent.
6. Pregnancy or lactation.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. This study will have two co-primary endpoints: • To demonstrate a 50% reduction in 30-day mortality for carriers developing a pre-engraftment bloodstream infection sustained by carbapenem-resistant Enterobacteriaceae (CRE) or Pseudomonas aeruginosa (PA) (earlier primary endpoint). To increase by 20% the Overall Survival (OS) at 4 months from the start of intensive treatment in all carriers of CRE or PA compared to historical controls (later primary endpoint).

Secondary endpoints 3

1. OS in CRE or PA carriers not developing a bloodstream infection sustained the colonizing agent at 4 months from the start of intensive chemotherapy or transplant; Days of fever > 38.3°C at 30 days from the day of start intensive chemotherapy or from day of transplant. Days of hospitalization at 30 days from the start of intensive chemotherapy or from day of transplant; Days of i.v. antimicrobials at 30 days from the start of intensive chemotherapy or from day of transplant.
2. Non-relapse mortality (NRM) at 4 months from the start of intensive chemotherapy or transplant; Incidence and severity of adverse drug reactions (ADR) classified by System Organ Class (SOC) and preferred term (PT) at 30 days from start treatment with Pentaglobin; Incidence and severity of acute GvHD at 120 days from day of transplant. Incidence and severity of chronic GvHD at 1 year day of transplant.
3. The cumulative incidence of graft failure / time to neutrophil and platelet recovery at 30 and 60 days from the day of start intensive chemotherapy or from day of transplant. One year probability of GRFS (GvHD free, relapse free survival) from the day of start intensive chemotherapy or from day of transplant.

Investigational products

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

Test 1

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

Trial Office GITMO

Public contact point

Organisation

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

Contact name

Segreteria GITMO

Locations

1 EU/EEA country · 6 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 5 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