Acute graft versus host disease after allogeneic hematopoietic stem cell transplantation or donor lymphocyte infusion MedDRA version: 20.1 Level: PT Classification code 10066260 Term: Acute graft versus host disease System Organ Class: 10021428 - Immune system disorders
Conditions
Interventions
Product Name: BEGEDINA 2.0 mg/ml concentrate for solution for infusion
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: -
CAS Number: 1403744-56-8
Current Sponsor code:
Sponsors
ADIENNE SA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: ?Age =12 and =70 years old. ?Subject must be willing and able to comply with study requirements, remain at the clinic, and return to the clinic for the follow-up evaluation, as specified in this protocol during the study period. ?Subject must be able and willing to provide signed informed consent. For patients aged 40%. ?Lansky performance score = 70% for patients aged <16 years or Karnofsky performance score =50% for patients aged = 16 years). ?Life expectancy of greater than 1 month. ?Women of child-bearing potential and men must agree to take adequate contraceptive measures in order to avoid any pregnancies of their sexual partners during the course of the study (or for at least 3 months following the last dose of study drug, whichever is longer). Acceptable methods of birth control include oral, injected or implanted hormonal methods of contraception, placement of an intrauterine device IUD) or intrauterine system (IUS), barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/ film/ cream/suppository. Abstinence is only considered an acceptable form of contraception when it is the usual life style of an individual. ?Women must have a negative pregnancy test at Screening and at Baseline and must not be breastfeeding. Are the trial subjects under 18? yes Number of subjects for this age range: 20 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects
Exclusion criteria
Exclusion criteria: ?Patients transplanted with ex vivo T-cell-depleted grafts. ?Patients with signs of steroid-resistance. ?Participants with manifestations of chronic GvHD. ?Participants with acute/chronic GvHD overlap syndrome. ?Patient with evidence of relapsed/persistent malignancy. ?Patients with adequate renal reserve as defined by serum creatinine = 3× ULN or calculated creatinine clearance (CLcr) = 30 mL/min using the Cockroft-Gault equation. ?Lansky performance score =70 for patients aged 1 liter ?Patients with uncontrolled bacterial, viral or fungal infections ?Uncontrolled diabetes at the time of cytoreduction. ?Evidence of HIV seropositivity and/or positive PCR assay, HTLV1 / HTLV2 seropositivity. ?Evidence of seropositivity for hepatitis B virus surface antigen (HBsAg) and/or anti-hepatitis C virus (anti-HCV) antibodies. Serologic positivity in the absence of detectable HBV or HCV DNA/RNA will not be exclusion criteria. ?Evidence of a clinically relevant CMV-viremia. Clinically relevant CMV-viremia is defined as detection of viral load =5000 copies/mL in whole blood, as measured by quantitative PCR. ?A history of prolonged QTc syndrome. ?Administration of any other investigational agents (not approved by the United States Food and Drug Administration Agency [FDA] or European Medicines Agency [EMA] for any indication) within 4 weeks prior to enrolment. Participation in any clinical trial for prevention of acute GvHD or within 5 half-lives of the study treatment (whichever is longer) within 4 weeks of the screening visit. ?Known hypersensitivity to murine proteins. ?Women who are pregnant, breastfeeding or at risk to become pregnant during study participation; female patients of childbearing potential who have not been started on an anti-ovulatory regimen prior to initiation of chemo-inductive regimen must test negative for pregnancy (serum) at the Baseline Visit. ?Unwillingness to use effective contraceptive measures up to 3 months after the end of study drug administration (females and males). Acceptable methods of birth control include oral, injected or implanted hormonal methods of contraception, placement of an intrauterine device IUD) or intrauterine system (IUS), barrier methods of contracept
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objectives of the trial will be: •to establish the optimal biological dose (OBD) of intravenously infused begelomab in terms of modulation of CD26/CD3 lymphocyte activity; •to investigate the pharmacokinetics and pharmacodynamics of begelomab following escalating multiple doses of begelomab; •to investigate efficacy endpoints; •to investigate the safety and tolerability of multiple doses of begelomab in patients with acute Graft-versus-Host Disease. ;Secondary Objective: •Cumulative overall response at Day 28, Day 56, Day 100 and Day 180 •Duration of overall response •Overall response of grade II-IV visceral acute GvHD at Day 28, Day 56, Day 100 and Day 180 •Incidence and severity of systemic infections •Overall Survival at Day 28, Day 56, Day 100 and Day 180 •GvHD relapse-free survival at Day 100 and Day 180 •Transplant-related mortality at Days 28, 56, 100 and 180 •Cumulative dose of steroid treatment •Percentage reduction of the steroid dose compared with respect to initial dosing •Incidence of steroid-resistant acute GvHD at Day 28, Day 56, Day 100 and Day 180 •Incidence of chronic GvHD at Day 100 and Day 180 Pharmacokinetics of begelomab •Incidence and titre time-course of HAMA •Time course of circulating CD26+ •AE and AE)incidence •Proportion of participants who have a TRAE after infusion of begelomab ;Primary end point(s): The primary endpoint of the study will be the dose of begelomab leading to a maximum receptor occupancy within the tested dose range 4.0 – 25.0 mg/m2/day, as determined with flow cytometry.;Timepoint(s) of evaluation of this end point: throughout treatment period | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Cumulative overall response at Day 28, Day 56, Day 100 and Day 180 •Duration of overall response •Overall response of grade II-IV visceral acute GvHD at Day 28, Day 56, Day 100 and Day 180 •Incidence and severity of systemic infections •Overall Survival at Day 28, Day 56, Day 100 and Day 180 •GvHD relapse-free survival at Day 100 and Day 180 •Transplant-related mortality at Days 28, 56, 100 and 180 •Cumulative dose of steroid treatment •Percentage reduction of the steroid dose compared with respect to initial dosing •Incidence of steroid-resistant acute GvHD at Day 28, Day 56, Day 100 and Day 180 •Incidence of chronic GvHD at Day 100 and Day 180 • Pharmacokinetics of begelomab as determined by the Cmax, tmax, AUC0-t, CL, t1/2?z, and the accumulation ratios for Cmax and AUC • Incidence and titre time-course of human anti-murine antibody (HAMA) and its neutralizing ability •Time course of circulating CD26+ • Adverse Event (AE) and Serious Adverse Event (SAE) incidence • Proportion of participants who have a treatment-related AE (TRAE) after infusion of begelomab •Exploratory endpoints: will be exploratory biomarkers ;Timepoint(s) of evaluation of this end point: Cumulative OR, OR of grade II-IV visceral acute GvHD at Day 28, 56,100,180 Duration of OR from baseline to Day 180 Incidence and severity of systemic infections Day 28,100,180 GvHD relapse-free survival at Day 100,180 Transplant-related mortality at Days 28,56,100,180 Cumulative dose of steroid treatment Day 7,15,8,56,100,180 Percentage reduction of the steroid dose compared to initial dosing Day 28, 56,100,180 Incidence of steroid-resistant acute GvHD at Day 28,56,100,180 chronic GvHD at Day 100,180 Pharmacokinetics of begelomab from Day 1 to 31 Incidence and titre time-course of HAMA Time course of circulating CD26(-1 to Day 180) AE/SAE from baseline to Days 28,100,180 TRAE after infusion from baseline to Days 28,100,180 Exploratory biomarkers: f | — |
Countries
Italy
Contacts
Public ContactChief Scientific Officer
ADIENNE SA
Outcome results
None listed