Grappa

Overview

Sponsor-declared trial summary

Key facts

Sponsor

DKMS Group gGmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

28 Jan 2022 → 31 Mar 2026

Decision date (initial)

2024-09-20

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-510441-24-00

EudraCT number

2021-000853-17

ClinicalTrials.gov

NCT05153226

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis, Therapy

One of the key elements to improve allogeneic HCT is the administration of optimized
conditioning treatment including immunosuppressive drugs to facilitate engraftment, prevent
GVHD and induce tolerance of donor immune cells.
Specifically, the goal of this trial is to investigate the impact of PTCY versus ATG Grafalon ®
as part of a conditioning treatment for alloHCT on overall survival (OS) and on graft-versus host
disease-free and relapse-free survival (GRFS).
Information on the investigational drugs provided by these two endpoints will enable the
scientific community a comprehensive assessment of the two approaches for alloHCT.

Secondary objectives 1

1. Data collected within this trial will further allow: − to assess the risk of acute and chronic GVHD, relapse and NRM after alloHCT per treatment arm. − to evaluate risk factors for acute and chronic GVHD, relapse, and NRM. − to test for interactions between the presence or absence of (specific) HLA mismatches and major alloHCT outcomes. − to test for interactions between sex mismatches and major alloHCT outcomes. − to describe organ-specific clinical patterns of GVHD depending on the study arm.

Conditions and MedDRA coding

Graft Vs Host Disease Peripheral Blood Stem Cell Transplantation AML MDS MDS/MPN CMML

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. Signed written Informed Consent and able to understand the nature of the trial and the trial related procedures and to comply with them (see Section 24.3). − Age ≥ 18 years. − One of the following eligible diagnoses: - AML in CR1 with intermediate or adverse risk genetic abnormalities (according to the ELN 2022 guidelines1), or undefined risk. - AML of any ELN risk category after hematological or molecular relapse0F a, or with primary refractory disease. - AML arising from myelodysplastic syndrome (MDS) or a myeloproliferative neoplasia, except if favourable genetic abnormalities (according to ELN 2022 guidelines1) are present. - Therapy-related myeloid neoplasia (t-MN), except if favourable genetic abnormalities (according to ELN 2022 guidelines1) are present. - MDS with intermediate risk, high risk or very high risk disease according to the IPSS-R Score or MDS with moderate high, high, or very high risk disease according to the IPSS-M Score2 regardless of treatment status. - MDS/MPN and CMML-1/CMML-2 according to WHO 20223 regardless of treatment status. − The left ventricular ejection fraction (LVEF) was ≥40% at last assessment. − Planned transplantation with Peripheral Blood Stem Cells (PBSC). − Transplantation scheduled to be performed 4 to 14 days after date of randomization. − The scheduled donor is unrelated to the patient, and matched or partially matched (with not more than one allele or antigen mismatch) at HLA-A, -B, -C, or -DRB1. − Absence of pregnancy confirmed by highly sensitive pregnancy test for WOCBP (see Section 17.7). Test must not date back - more than 3 days prior to randomization, or - more than 3 days prior to start of conditioning, if it started before randomization.

Exclusion criteria 1

1. − Anamnestic intravenous or subcutaneous exposure to rabbit immunoglobin-preparations (e.g. Grafalon  or Thymoglobulin ) − Known hypersensitivity to ATG Grafalon ® or its excipients. − Known hypersensitivity to cyclophosphamide, its metabolites or excipients. − Prior allogeneic hematopoietic transplantation. − Patients who receive supplementary continuous oxygen at the time of randomization. − Symptomatic heart failure (NYHA ≥2) at the time of randomization. − Uncontrolled viral, bacterial or fungal infection with progression or no clinical improvement at the time of randomization. − Symptomatic cystitis or known obstruction of urine flow at the time of randomization. − Breast-feeding women. − WOCBP and fertile male patients unable or unwilling to follow highly effective contraception methods from enrollment to minimum six months after the last dose of the IMP (see Section 17.7). − Simultaneous participation in another interventional clinical trial with an investigational medicinal product.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. (1) overall survival (OS) from randomization, and (2) graft-versus-host disease-free and relapse-free survival (GRFS) from time of transplantation.

Secondary endpoints 1

1. − Overall survival from HCT. − Relapse- and immunosuppression-free survival (RIFS) from HCT. − Event-free survival (EFS) from HCT. − Cumulative incidences of relapse from HCT. − Cumulative incidences of non-relapse mortality (NRM) from HCT, etc. (s.protocol section 10.2).

Investigational products

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

Test 3

Comparator 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

DKMS Group gGmbH

Sponsor organisation

DKMS Group gGmbH

Address

Kressbach 1, Weilheim Weilheim

City

Tuebingen

Postcode

72072

Country

Germany

Scientific contact point

Organisation

DKMS Group gGmbH

Contact name

Sarah Trost

Public contact point

Organisation

DKMS Group gGmbH

Contact name

Sarah Trost

Locations

1 EU/EEA country · 25 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 8 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