Efficacy Study on the Strategy of Herpes Simplex Virus Thymidine Kinase (HSV-Tk) Donor Lymphocytes to Treat Patients With High Risk Acute Leukemia - Full Text View

Sponsored by:	MolMed S.p.A.
Information provided by:	MolMed S.p.A.
ClinicalTrials.gov Identifier:	NCT00914628

Purpose

The objective of this randomized trial is to demonstrate the superiority in terms of non-relapse mortality (NRM) reduction and overall survival improvement of HSV-TK add back strategy versus a standard strategy following haploidentical hematopoietic cell transplantation (HCT) in patients with acute high risk leukemia.

Primary aims:

To compare the cumulative incidence of NRM in high risk leukemia patients who underwent haploidentical HCT followed by add back strategy of HSV-TK donor lymphocytes or standard haploidentical HCT.
To compare the overall survival (OS) in the two treatment arms.

Secondary aims

To compare engraftment rate, cumulative incidence of grade II-IV acute GvHD, time to T-cell immune reconstitution and extensive chronic graft versus host disease (GvHD) in the two treatment arms.
To compare incidence and duration of infectious episodes and infectious disease mortality in the two treatment arms.
To compare cumulative incidence of relapse (CIR) and disease-free survival (DFS) in the two treatment arms.
To evaluate the acute and long-term toxicity related to the HSV-Tk infusions.
To assess quality of life (QoL) and Medical Care Utilization (MCU) in both arms.

Condition	Intervention	Phase
High Risk Acute Leukemia	Genetic: HSV-Tk Other: T cell repletion strategies	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
Official Title:	TK008: Randomized Phase III Trial of Haploidentical HCT With or Without an Add Back of Strategy of HSV-Tk Donor Lymphocytes in Patients With High Risk Acute Leukemia.

Resource links provided by NLM:

MedlinePlus related topics: Leukemia, Adult Acute Leukemia, Adult Chronic

U.S. FDA Resources

Further study details as provided by MolMed S.p.A.:

Primary Outcome Measures:

Overall Survival (OS) measured for all patients from the date of randomization until death from any cause. [ Time Frame: From randomization to death ] [ Designated as safety issue: Yes ]
Non-Relapse Mortality (NRM) defined for all patients as the probability of death related to transplantation and not to relapse (considered as competing event). [ Time Frame: From the date of HCT until to death ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Engraftment rate defined as the persistent blood cells count above a predefined level (ANC ≥ 1x10^9/L per 3 consecutive days with evidence of donor haematopoiesis; platelets ≥ 50x10^9/L, unsupported by transfusions, for 7 days). [ Time Frame: Weekly up to IR after HCT or up to 6 months after HCT if no IR ] [ Designated as safety issue: Yes ]
Cumulative incidence of grade 2, 3, or 4 acute GVHD (aGvHD), diagnosed and graded according to standard criteria, will be computed in patients who will survive. [ Time Frame: During the first 100 days after HCT ] [ Designated as safety issue: Yes ]
Immune reconstitution (IR) will be defined as the time to reach a level of circulating CD3+ ≥ 100/μl for two consecutive observations. [ Time Frame: Weekly after HCT ] [ Designated as safety issue: Yes ]
Cumulative incidence of relapse (CIR) defined on the basis of morphologic evidence of leukaemia in bone marrow or other sites (considering death without evidence of relapse as competing event). [ Time Frame: From the data of HCT until the date to the first occurrence of relapse ] [ Designated as safety issue: Yes ]
Disease-Free Survival (DFS) will be measured for all patients from the date of transplantation until the date of relapse or death from any cause, whichever occurs first. [ Time Frame: From the date of HCT until the date of relapse or death ] [ Designated as safety issue: Yes ]
Cumulative incidence of extensive chronic GvHD (cGvHD) diagnosed and graded according to standard NIH consensus criteria, will be computed in patients who will survive. [ Time Frame: For at least 100 days after transplantation ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	152
Study Start Date:	April 2008
Estimated Study Completion Date:	May 2012
Estimated Primary Completion Date:	May 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Experimental	Genetic: HSV-Tk Infusion of 1x10^7 HSV-Tk genetically modified CD3+ cells/Kg between day +21 and day +49 after haploidentical HCT
B: Active Comparator	Other: T cell repletion strategies Haploidentical HCT with the infusion of CD34+ cells plus a fixed dose of T cells (1 x 10^4/Kg)

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age ≥ 18 years
Any of the following conditions:
- AML and ALL in 1st complete remission (CR) at high risk of relapse based on negative prognostic factors
- AML and ALL in 2nd or subsequent CR
- secondary AML in CR
Absence of HLA matched family or unrelated donor
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

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

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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00914628

Contacts

Contact: Fabio Ciceri, MD

+39 02 2643

Locations

Italy
Fondazione San Raffaele	Recruiting
Milan, Italy
Contact: Fabio Ciceri, MD +39 02 2643

Sponsors and Collaborators

MolMed S.p.A.

Investigators

Principal Investigator:

Fabio Ciceri, MD

Fondazione San Raffaele

More Information

No publications provided

Responsible Party:	Molmed ( Molmed )
Study ID Numbers:	TK008, Eudract: 2006-006862-41
Study First Received:	June 3, 2009
Last Updated:	June 4, 2009
ClinicalTrials.gov Identifier:	NCT00914628 History of Changes
Health Authority:	Italy: National Institute of Health

Keywords provided by MolMed S.p.A.:

high risk acute leukemia
HSV-TK
Haploidentical HCT

GvHD
GvL
Immunoreconstitution

Study placed in the following topic categories:

Acute Disease
Virus Diseases
Herpes Simplex
Leukemia

Additional relevant MeSH terms:

Acute Disease
Leukemia
Disease Attributes

Neoplasms
Pathologic Processes
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on September 03, 2009