A multi-center randomized phase II study comparing corticosteroids alone versus corticosteroids and extracorporeal photopheresis as first-line treatment of Grade II acute graft-versus-host disease with skin involvement occuring after allogeneic stem cell transplantation - COPAVEHDI

Overview

Sponsor-declared trial summary

Key facts

Sponsor

CHRU De Nancy

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

15 Oct 2024 → ongoing

Decision date (initial)

2024-03-20

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-508614-41-00

ClinicalTrials.gov

NCT06133192

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To compare the percentage of patients who are not in treatment failure at 6 months from the start of treatment for acute GVH between the conventional treatment arm (corticosteroids alone) and the experimental arm (corticosteroids + ECP).

Secondary objectives 10

1. Comparison of the 2 groups (experimental strategy versus standard of care), after randomization on the cumulative dose of steroids over time,
2. Comparison of the 2 groups (experimental strategy versus standard of care), after randomization on the incidence rate of infections (bacteremia, septicemia, fungal infections, parasite and virus reactivation),
3. Comparison of the 2 groups (experimental strategy versus standard of care), after randomization on the incidence of thrombotic complications
4. Comparison of the 2 groups (experimental strategy versus standard of care), after randomization on the incidence and severity of chronic GVHD,
5. Comparison of the 2 groups (experimental strategy versus standard of care), after randomization on the non-relapse mortality rate,
6. Comparison of the 2 groups (experimental strategy versus standard of care), after randomization on the incidence of disease relapse,
7. Comparison of the 2 groups (experimental strategy versus standard of care), after randomization on the disease-free survival (DFS),
8. Comparison of the 2 groups (experimental strategy versus standard of care), after randomization on the overall survival,
9. Comparison of the 2 groups (experimental strategy versus standard of care), after randomization on the health-related quality of life
10. Comparison of the 2 groups (experimental strategy versus standard of care), after randomization on the immune reconstitution (T, B, NK cells, gamma globulins)

Conditions and MedDRA coding

The study will be proposed to all adult patients receiving an allogeneic hematopopietic stem cell transplantation and presenting a Grade II acute GVH with skin +/- upper gastrointestinal involvement, in transplant centers contributing to this trial (departments of hematology).

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Age > 18 years
2. allogeneic hematopoietic stem cell transplantation received (from any type of graft and donor) after malignant or non malignant disease
3. patient suffering from Grade II acute GVHD with skin +/- upper Gastrointestinal tract involvement (stage 2-3 skin + stage 1 upper gastrointestinal tract or isolated skin stage 3) in the 3 months following stem cell transplantation
4. patient requiring first line therapy to treat acute GVHD,
5. patient able to start ECP therapy in the 3 days after randomization
6. validation of the presence of a peripheral or central venous access (its type should be conform to the recommendations described in the Therakos Cellex operator manual, Annex 3), allowing to perform PCE sessions weekly during 3 months. In the absence of appropriate preexisting central line at inclusion, peripheral access will be preferred.
7. Leukocytes > 1.5 G/L based on the last available blood testing results,
8. Platelets > 30 G/L, hematocrit > 27% (blood transfusion are permitted), based on the last available blood testing results,
9. An individual affiliated to a social security scheme or beneficiary of such a scheme
10. An individual who has received full information about how the clinical trial will be conducted and has signed an informed consent form
11. An individual who has undergone clinical screening adapted to the clinical trial,

Exclusion criteria 15

1. Grade 1 acute GVHD,
2. Included in another prospective study of acute GVH treatment
3. Acute GVHD grade > II or acute GVH with lower tract gastrointestinal tract or with liver involvement,
4. Hematologic disease relapse at time of acute GVHD,
5. uncontrolled ongoing infection at time of inclusion: bacterial or fungal infections, CMV reactivation with increasing CMV viral load
6. HIV positivity or replicative HBV or HCV infection (based on pre-transplant assessment),
7. Pregnant or breast feeding female
8. Women of childbearing age without effective contraception
9. Patient with allergy or contraindications to UVADEX : 1/ Known 8 MOP allergy 2/ Melanoma, basal cell, or squamous cell skin carcinoma, 3/ Phenytoin treatment
10. Patient with contraindications to posaconazole (NOXAFIL®): 1/Hypersensitivity to active ingredient or excipients,2/Ongoing treatment with ergot alkaloids, 3/Ongoing treatment with one CYP3A4 substrate which could lead to increased plasma concentration of these drugs, and so can result in QTc interval prolongation and rare cases of Torsade de Pointe (terfenadine, astemizole, cisapride, pimozide, halofantrin, quinidine), 4/Ongoing treatment with inhibitors of the HMG-CoA reductase (simvastatin, lovastatin, atorvastatin) due to greater risk of rhabdomyolysis, 5/Ongoing or scheduled treatment with venetoclax
11. Ongoing or scheduled treatment on short-term perspective with vinca-alkaloids
12. Patients with medical history corresponding to contra-indications to photopheresis:1/ aphakia, 2/photosensitive disease (e.g., porphyria, systemic lupus erythematosus, albinism), 3/cardiac insufficiency, 4/previous splenectomy, 5/coagulation abnormalities, 6/heparin-induced thrombocytopenia, 7/uncontrolled digestive bleeding
13. Patients with contra-indication to steroids:1/Allergy to prednisone or methylprednisolone, 2/Uncontrolled psychotic disease
14. patient with previous deep vein thrombosis in the last 5 years,
15. Patient with ongoing psychiatric cares as described in act L.3212-1 et L.3213-1 of the French Public Health code:1/Individuals referred to in Articles 10, 31, 32, 33 and 34 of Regulation (EU) No 536/2014, 2/Minor (not emancipated), 3/Adult subject to a legal protection measure (such as guardianship, conservatorship), 4/Adult who is unable to give consent

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percentage of patients without treatment failure at 6 months in each arm. Absence of treatment failure is defined by meeting all the following 4 conditions at 6 months from randomization:1/to be alive, 2/without relapse of the hematological disease, 3/without having required a new line of treatment for acute GVHD,4/without initiating a systemic treatment for chronic GVHD

Secondary endpoints 10

1. The mean of the cumulative dose of steroids over time (randomization-1 month, 1-2 month, 2-3 month, 3-6 month and 6-12 month periods),
2. The cumulative incidence rate of infections at 6 and 12 months (bacteremia, septicemia, fungal infection and virus reactivation),
3. The cumulative incidence of thromboembolic complications at 3 months (diagnosed with Doppler ultrasound exam and/or CT coronary angiogram performed in case of indicative clinical symptoms)
4. the incidence and severity of chronic GVHD (according to NIH criteria19) at 6 and 12 months after randomization (see Annex 4),
5. the non-relapse mortality rate at 6 and 12 months (death due to any cause except underlying disease relapse)
6. the incidence of underlying disease relapse at 6 and 12 months after randomization (relapse is defined on the basis of morphological evidence of leukemic or lymphoma cells in the bone marrow or other sites),
7. the disease-free survival at 6 and 12 months after randomization (time from randomization date to either first relapse or death from any cause),
8. the overall survival at 6 and 12 months after randomization (time from randomization date to either first relapse or death from any cause)
9. the mean scores of health-related quality of life using the French validated FACT-BMT (version 4.0, see Annex 5) at 3, 6 and 12 months after transplant,
10. immune reconstitution based on peripheral blood testing (rate of total T lymphocytes, CD4 and CD8 T cells, B cells, NK cells, gamma globulins) at 3, 6 and 12 months after randomization (depending on usual practices in each center).

Investigational products

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

Test 1

Comparator 2

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

CHRU De Nancy

Sponsor organisation

CHRU De Nancy

Address

Co N°34, 29 Avenue Du Mal De Lattre De Tassigny, Bp 60034 29 Avenue Du Mal De Lattre De Tassigny Bp 60034

City

Nancy Cedex

Postcode

54035

Country

France

Scientific contact point

Organisation

CHRU De Nancy

Contact name

RUBIO Marie-Therese

Public contact point

Organisation

CHRU De Nancy

Contact name

RUBIO Marie-Therese

Locations

1 EU/EEA country · 11 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 50 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