AML or ALL in complete remission at high risk of relapse
Conditions
Interventions
ARM A (experimental group):
Haploidentical HCT with the infusion of CD34+ cells plus a fixed dose of T
cells (1 x 10/4/Kg), followed by:
- Infusion of approximately 1 x 10/7 HSV-Tk genetically modifi
Sponsors
MolMed S.p.A
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: • Age >= 18 with HCT comorbidity index < 3 (Appendix I);• Any of the following conditions:;• AML and ALL in 1st complete remission (CR) at high risk of relapse based on negative prognostic factors (for the definition of high-risk of relapse see Appendix H);• AML and ALL in 2nd or subsequent CR;• secondary AML in CR;• Absence of timely and suitable fully HLA matched or one HLA locus mismatched family or unrelated donor and, at Investigator*s discretion, absence of other possible therapeutic alternatives;• Stable clinical conditions and life expectancy > 3 months;• PS ECOG < 2;• Serum creatinine < 1.5 x ULN;• Bilirubin < 1.5 x ULN; transaminases < 3 x ULN;• Left ventricular ejection fraction > 45%;• QTc interval < 450 ms;• DLCO > 50%;• Patients and donors, or independent witnesses must sign an informed consent indicating that they are aware this is a research study and have been told of its possible benefits and toxic side effects.
Exclusion criteria
Exclusion criteria: • Patients with life-threatening condition or complication other than their basic disease;• Contraindication to haploidentical HCT as defined by the Investigator;• Patients with active CNS disease;• Pregnant or lactation. Patients both males and females with reproductive potential (i.e. menopausal for less than 1 year and not surgically sterilized) must practice effective;contraceptive measures throughout the study. Women of childbearing potential must provide a negative pregnancy test (serum or urine) within 14 days prior to registration.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary efficacy parameter: - Disease-Free Survival (DSF) will be measured for all patients from the date of randomization until the date of relapse or death from any cause, whichever occurs first | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary efficacy parameters: - Overall Survival (OS) will be measured for all patients from the date of randomization until death from any cause - Non-relapse mortality (NRM) will be defined for all patients as any death without previous occurence of a documented relapse - Immune Reconstitution (IR) will be defined as the time to reach a level of circulating CD3+ >= 100/µl - Engraftment rate will be defined as the persistent blood cells count above a predefined level (ANC >= 1 x 109/L per 3 consecutive days with evidence of donor haematopoiesis; platelets >= 50 x 109/L, unsupported by transfusions, for 7 days) - Cummulative incidence of grade 2, 3 or 4 acute GvHD, diagnosed and graded according to standard criteria, will be computed from the transplantation - Cummulative incidence extensive chronic GvHD, diagnosed and graded according to standard criteria, will be computed from the transplantation - Cummulative incidence of relapse will be defined on the basis of morphologic evidence of leukaemia in bone marrow or other sites. Safety and tolerability parameters: - Adverse Events (AE) and laboratory abnormalities graded according tot the CTCAE v 4.02 - laboratory assessments (urinalisis, hematology, blood chemistry, immunophenotype, PCR-TK, RCR analysis), bone marrow asprirate - physical examination and vital signs - Serious Adverse Events (SAE) - Suspected Unexpected Serious Adverse Reactions (SUSARs) - Long term follow up Quality of life: FACT-BMT to summarize and evaluate patient convenience and satisfaction Pharmacoeconomics on medical care utilization. To summarize and evaluate treatment group differences. | — |
Countries
Netherlands
Outcome results
None listed