Prospective, phase II/III, randomized clinical study to compare BEGEDINA® versus conventional treatment for treating steroid resistant acute graft-versus host disease.

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 184

Inclusion Criteria

1. Age >=18 and <=65 years of age.
2. Recipient of an allogeneic hematopoietic stem cell transplantation(HSCT).Note: Subjects with steroid resistant GvHD following donor lymphocyte infusion post HSCT are also eligible
3. Steroid-resistant acute GvHD, Grade II-IV, defined as:
- progressive disease after 3 days of primary treatment with methylprednisolone 2 mg/kg, or equivalent.
or
- lack of at least a partial response after 7 days of primary treatment with methylprednisolone 2 mg/kg or equivalent.
or
- lack of a complete response after 14 days of primary treatment with methylprednisolone 2 mg/kg or equivalent.
Note: Subjects who may have received an increase in their steroid dose treatment prior to randomization will be eligible for enrollment. An increase in steroid dose will not be considered as second-line therapy.
4. Evidence of myeloid engraftment (absolute neutrophil count >=0.5 x 109/L) .
5. Karnofsky Performance Status Scale >=50%.
6. Adequate renal function as defined by serum creatinine <=2 × upper limit of normal or calculated creatinine clearance (CrCl) of >=30 mL/min using the Cockroft-Gault equation: Calculated CrCl= ([140-age in years] x [ideal body mass {IBM} in kg])/72 x (serum creatinine value in mg/dL), where IBM = IBM (kg) = ([height in cm?154] × 0.9) + (50 if male, 45.5 if female).
7. Subject must be willing and able to comply with the 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.
8. Able and willing to provide signed informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 184
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

1. Prior second-line systemic treatment for GvHD.
2. Received agents other than steroids for primary treatment of acute GvHD.
3.Acute steroid resistant GvHD beyond 28 days from first-line therapy (primary treatment).
4.Stage 1-2 skin acute GvHD alone (with no other organ involvement).
5. Evidence of severe hepatic veno-occlusive disease or sinusoidal obstruction.
6. Evidence of encephalopathy.
7. Life expectancy <3 weeks.
8. Presence of chronic GvHD
9. Second or subsequent allogeneic transplant.
10. Previous solid organ transplant (with the exception of a corneal transplant >3 months prior to screening).
11. Relapsed disease after last transplant.
12. Human immunodeficiency virus positive.
13. Evidence of lung disease that is likely to require more than 2LPM of O2 via face mask or an estimated FiO2 of 28% via other delivery methods in order to sustain an O2 saturation of 92% within the next 3 days.
14.Any underlying or current medical or psychiatric condition that, in the opinion of the Investigator, would interfere with the evaluation of the subject including uncontrolled infection, heart failure, pulmonary hypertension. Any other serious medical condition, as judged by the investigator, which places the subject at an unacceptable risk if he or she were to participate in the study or confounds the ability to interpret data from the study.
15.Administration of any other investigational agents (not approved by the United States Food and Drug Agency/European Medicines Agency [FDA/EMA] for any indication) within 30 days of randomization. Participated in any interventional clinical trial for an acute GvHD therapeutic agent or for an immunomodulatory drug, within the past 30 days or within 5 half-lives of the study treatment, whichever is the greater. Participated or is currently participating in any bone marrow derived autologous and allogeneic stem cell or gene therapy study.
16. Known allergy to murine proteins.
17. Women who are pregnant, breastfeeding or at risk to become pregnant during study participation; female subjects 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 time of enrollment.
18. Male and female subjects who do not agree to take adequate measures to avoid pregnancy (including abstinence) prior to study entry and for the duration of participation in the study (or for at least 3 months following the last dose of study drug, whichever is longer). See section 6.2.1.6 for acceptable methods of birth control.