Efficacy Study on the Strategy of HSV-Tk Engineering Donor Lymphocytes to Treat Patients With High Risk Acute Leukemia
Condition: Acute Leukemia (Category)
MeSH terms: Leukemia; Acute Disease
Intervention: HSV-Tk; T-cell depleted or T-cell replete strategies
Intervention description: Infusion of approximately 1±0.2 x 10^7 HSV-Tk genetically modified CD3+ cells/Kg between day +21 and day +49 after haploidentical HCT; in absence of immune reconstitution and GvHD further infusions up to 4 will be administered on monthly basis.; Haploidentical HCT with the infusion of CD34+ cells plus a fixed dose of T cells (1 x 10^4/Kg) or unmanipulated haploidentical stem cell transplantation followed by high-dose cyclophosphamide as part of GvHD prophylaxis
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 92.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: high risk acute leukemia; HSV-TK; Haploidentical HCT; GvHD; GvL; Immunoreconstitution

Summary:

      The main objective of this randomized trial is to compare disease-free survival (DFS) in high
      risk leukemia patients who underwent haploidentical HCT followed by an add back strategy of
      HSV-Tk donor lymphocytes or standard haploidentical HCT
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age ≥ 18 years

          -  Any of the following conditions:

               1. AML and ALL in 1st complete remission (CR1)

               2. AML and ALL in 2nd or subsequent CR

               3. secondary AML in CR

               4. AML and ALL in 1st or 2nd relapse or primary refractory

          -  Family donor with patient-donor number of HLA mismatches ≥ 2 (full haploidentical), or
             family donors sharing one HLA-haplotype with the patient

          -  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, or legal guardians, and donors 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:

          -  Patients with life-threatening condition or complication other than their basic
             condition

          -  Contraindication to haploidentical HCT as defined by the Investigator

          -  Patients with active CNS disease

          -  Pregnant or lactation.

        Exclusion criteria for HSV-Tk infusion:

          -  Infections requiring administration of ganciclovir or valganciclovir at the time of
             infusion

          -  GvHD requiring systemic immunosuppressive therapy

          -  Ongoing systemic immunosuppressive therapy after haploidentical HCT

          -  Administration of G-CSF after haploidentical HCT

        HSV-Tk cells can be administered after an adequate patient wash-out period (24 hours)