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TK008 Randomized Phase III Trial of Haploidentical HCT With or Without an Add Back Strategy of HSV-Tk Donor Lymphocytes in Patients With High Risk Acute Leukemia

Phase 3
18 Years
Open (Enrolling)
High Risk Acute Leukemia

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Trial Information

TK008 Randomized Phase III Trial of Haploidentical HCT With or Without an Add Back Strategy of HSV-Tk Donor Lymphocytes in Patients With High Risk Acute Leukemia

Delayed immune-reconstitution remains one of the main limitation of haploidentical stem cell
transplantation. The risk of severe infections remains high for several months and CD4+
reconstitution could take more than 10 months. The low number of lymphocytes infused with
the graft, the degree of HLA disparity, and a reduced thymic function in adults and
differences in host/donor antigen presenting cells are contributing causes.

The infusions of HSV-TK engineered lymphocytes may represent a significant therapeutic
improvement in haploidentical HCT, because it remarkably may enhance both GvL activity, thus
reducing the occurrence of disease relapse, and post-transplant immune reconstitution in the
absence of chronic immune suppression, thus decreasing the rate of both post-transplant
opportunistic infections and transplant-related mortality. Furthermore, the efficient
control of GvHD achieved via the suicide mechanism allows also the multiple infusion of
HSV-TK-treated donor lymphocytes, when needed, that might further improve post-transplant
host immune reconstitution, and survival in patients receiving haplo-HCT. Finally, this
therapeutic approach can become a valuable option for all candidates, including patients
with advanced disease and older age.

The proposed clinical trial represents an innovative therapeutic treatment for patients
affected by high risk acute leukemia, who have undergone haploidentical stem cell

Inclusion Criteria:

- Age ≥ 18 years with HCT comorbidity index < 3

- 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 < or = 2

- 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

- 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%

Exclusion Criteria:

- Patients with life-threatening condition or complication other than their basic

- 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, valganciclovir or acyclovir at
the time of infusion: HSV-Tk cells can be administered after a 24-hour
discontinuation interval of antiviral therapy

- GvHD requiring systemic immunosuppressive therapy

- Ongoing systemic immunosuppressive therapy after haploidentical HCT

- Administration of G-CSF after haploidentical HCT

- CD3+ cells ≥ 100/µl at day of planned experimental infusion after haploidentical HCT

- Any grade 3-4 adverse event related to HSV-Tk infusion or a grade 2 adverse event
that does not resolve to no more than grade 1 before the next infusion

For criteria 2, 3 and 4: HSV-Tk cells can be administered after an adequate patient
wash-out period

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Disease-free survival (DFS)

Outcome Time Frame:

From the randomization date to relapse date or death

Safety Issue:


Principal Investigator

Fabio Ciceri, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fondazione San Raffaele


Italy: The Italian Medicines Agency

Study ID:




Start Date:

February 2010

Completion Date:

June 2016

Related Keywords:

  • High Risk Acute Leukemia
  • high risk acute leukemia
  • HSV-TK
  • Haploidentical HCT
  • GvHD
  • GvL
  • Immunoreconstitution
  • Leukemia
  • Acute Disease



Northwestern University Feinberg School of MedicineChicago, Illinois  60611
Washington University Medical SchoolSt. Louis, Missouri  63110