Efficacy Study on the Strategy of HSV-Tk Engineering Donor Lymphocytes to Treat Patients With High Risk Acute Leukemia (TK008)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00914628|
Recruitment Status : Recruiting
First Posted : June 5, 2009
Last Update Posted : September 14, 2018
|Condition or disease||Intervention/treatment||Phase|
|Acute Leukemia (Category)||Genetic: HSV-Tk Other: T-cell depleted or T-cell replete strategies||Phase 3|
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 CD3+ reconstitution could take more than 10 months. The low number of lymphocytes infused with the graft, the degree of HLA (Human Leukocyte Antigen) 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 (hematopoietic cell transplantation), because it remarkably may enhance both GvL (Graft versus Leukemia) 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 transplantation.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||170 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||February 2010|
|Estimated Primary Completion Date :||March 2021|
|Estimated Study Completion Date :||March 2021|
HSV-TK engineering donor Lymphocytes
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.
Active Comparator: B
T-cell depleted or T-cell replete strategies
Other: T-cell depleted or T-cell replete strategies
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
- Disease-free survival (DFS) [ Time Frame: from the date of randomization, assessed up to 12 months ]measured from the date of randomization until the date of relapse (or progression), or death from any cause, whichever occurs first.
- Overall Survival (OS) [ Time Frame: from the date of randomization to the date of death, assessed up to 12 months ]any death without previous occurrence of a documented relapse (or progression).
- Chronic GvHD-free/relapse-free survival (GRFS) [ Time Frame: from the date of randomization to the date of death, assessed up to 12 months ]the time from the date of randomization to chronic GvHD, relapse/progression or death from any cause, whichever occurs first.
- Immune reconstitution (IR) [ Time Frame: weekly up to IR after engraftment of HCT, monthly for 6 months from date of IR and then at month 9 and 12 ]the time to reach a level of circulating CD3+ ≥ 100/µl for two consecutive observations
- Engraftment rate [ Time Frame: day 15 after HCT, monthly for 6 months after HCT and then at month 9 and 12 ]defined as the persistent blood cells count above predefined level
- Cumulative incidence of grade 2, 3, or 4 acute GVHD (aGvHD) [ Time Frame: from the date of HCT until the date of the first occurrence of aGvHD, assessed up to 6 months ]diagnosed and graded according to standard criteria
- Cumulative incidence of chronic GvHD (cGvHD) [ Time Frame: from the date of HCT until the date of the first occurrence of cGvHD, assessed up to 12 months ]diagnosed and graded according to standard NIH consensus criteria
- Duration of GvHD episodes [ Time Frame: From the date of start until the date of resolution and duration of immunosuppressive treatments administered for controlling GvHD assessed up to 12 months ]Diagnosed and graded according to standard NIH consensus criteria
- Cumulative incidence of relapse (CIR) [ Time Frame: from the date of randomization to the date of the first occurrence of relapse, assessed up to 12 months ]Defined on the basis of morphologic evidence of leukaemia in bone marrow or other sites.
- Incidence and duration of infectious episodes and infectious disease mortality [ Time Frame: from randomization to the date of resolution, assessed up to 12 months ]diagnosis, monitoring and treatment of infectious relevant events
- Evaluate the acute and long-term toxicity related to the HSV-Tk infusions [ Time Frame: from HSV-Tk infusions to the date of resolution, assessed up to 12 months ]Toxicity profile of HSV-Tk infusions
- Quality of life (QoL) and Medical Care Utilization (MCU) in both arms [ Time Frame: from randomization up to 12 months ]Medical resource use data collected will be used in health economic analyses where it may be combined with other data from other sources such as cost data or other clinical parameters.
- Non-relapse mortality (NRM) [ Time Frame: from the date of randomization to the date of death, assessed up to 12 months ]Defined for all patients as any death without previous occurrence of a documented relapse (or progression)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00914628
|Contact: Fabio Ciceri, MD||0|
Show 36 Study Locations
|Study Director:||Antonio Lambiase, MD||MolMed S.p.A.|