Allogeneic hematopoietic cell transplantation from HLA-matched donor after Flu-Mel-PTCy versus Flu-Mel-ATG reduced-intensity conditioning: a phase II randomized study from the Belgian Hematology Society (BHS)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Liege

Participant type

Healthy volunteers, Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20], Diseases [C] - Neoplasms [C04]

Trial duration

4 Feb 2019 → ongoing

Decision date (initial)

2024-10-23

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-518568-11-00

EudraCT number

2017-000824-91

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis, Therapy, Safety

The present project aims at comparing two conditioning regimens (FM-PTCy vs FM-ATG). The hypothesis is that one or the two regimens will lead to a 2-year cGRFS rate improvement from 30% (the cGRFS rate with FM without ATG/PTCy) to 45% (Pick-a-winner phase 2 randomized study).

Conditions and MedDRA coding

Hematological malignancies confirmed histologically: - AML in morphological CR or not in morphological CR but not rapidly progressing (i.e. no need to give treatments such as hydroxyurea to maintain WBC count < 10 000 x109/mL); - MDS; - CML in CP or AP; - MPD not in blast crisis, - MDS/MPD overlap, - ALL in CR; - Multiple myeloma; - CLL; - Non-Hodgkin’s lymphoma (aggressive NHL should have chemosensitive disease); - Hodgkin’s disease with chemosensitive disease or responding to checkpoint inhibitors.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Disease: Hematological malignancies confirmed histologically: - AML in morphological CR or not in morphological CR but not rapidly progressing (i.e. no need to give treatments such as hydroxyurea to maintain WBC count < 10 000 x109/mL); - MDS; - CML in CP or AP; - MPD not in blast crisis, - MDS/MPD overlap, - ALL in CR; - Multiple myeloma; BHS-TC 14- Protocol Version 3.0 of 13JUNE2022 Page 10 / 32 - CLL; - Non-Hodgkin’s lymphoma (aggressive NHL should have chemosensitive disease); - Hodgkin’s disease with chemosensitive disease or responding to checkpoint inhibitors.
2. Clinical situations: • Theoretical indication for a standard allo-transplant, but not feasible because: - Age > 50 yrs; - Unacceptable end organ performance; - The physician’s decision; - The patient’s decision • Underlying ‘lower risk’ disease, for which RIC is preferred (eg CLL, MCL) • Continuation of maintenance with TKI are allowed after allo-HCT in case of Ph+ leukemia or FLT-3 mutated AML. Administration of other maintenance (defined as administration without evidence of relapse/progression of the underlying disease) treatments are not allowed in the protocol.
3. Other inclusion criteria: • Male or female; fertile patients must use a reliable contraception method; • Age 18-75 yrs (children of any age are not allowed in the protocol); • Informed consent given by patient or his/her guardian if indicated.

Exclusion criteria 1

1. Exclusion criteria: • Any condition not fulfilling inclusion criteria; • HIV positive; • Non-hematological malignancy(ies) (except non-melanoma skin cancer) active < 3 years before HCT. • Life expectancy severely limited by disease other than malignancy; • CNS involvement with disease refractory to intrathecal chemotherapy. • Terminal organ failure, except for renal failure (dialysis acceptable) a. Cardiac: Symptomatic coronary artery disease; ejection fraction <40%; uncontrolled arrhythmia, uncontrolled hypertension; b. Pulmonary: DLCO < 40% and/or receiving supplementary continuous oxygen, FEV1< 40%; c. Hepatic: Fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin >3 mg/dL, and symptomatic biliary disease; • Uncontrolled infection; • Karnofsky Performance Score <70%; • Patient is a fertile man or woman who is unwilling to use contraceptive techniques during and for 12 months following treatment; • Patient is a female who is pregnant or breastfeeding; • Any condition precluding the use of melphalan or ATG

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To assess the current GVHD-free, relapse-free survival (cGRFS) for patients conditioned with FM-PTCy or FM-ATG

Secondary endpoints 5

1. 1. To assess cGRFS for patients conditioned with FM-PTCy or FM-ATG separately in those transplanted with a related or an unrelated donor.
2. 2. To assess the relapse/progression rate for patients conditioned with FM-PTCy or FM-ATG.
3. 3. To assess the rates of grade II-IV and III-IV acute (at 6 months) and moderate/severe cGVHD (at 24 months) in patients conditioned with FM-PTCy or FM-ATG.
4. 4. To assess the rates of NRM as well as LFS and OS in patients conditioned with FM-PTCy or FM-ATG.
5. 5. To assess the proportion of patients alive without active disease and without systemic immunosuppression 1, 2, 3, 4, 5, 7, 10 and 15-years after transplantation in patients conditioned with FM-PTCy or FM-ATG.

Investigational products

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

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Liege

Sponsor organisation

Centre Hospitalier Universitaire De Liege

Address

Avenue De L'hopital 1

City

Liege

Postcode

4000

Country

Belgium

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Liege

Contact name

Josephine Muller

Public contact point

Organisation

Centre Hospitalier Universitaire De Liege

Contact name

Josephine Muller

Locations

1 EU/EEA country · 9 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 11 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