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Trial record 2 of 2 for:    molmed | Phase 3

Efficacy Study on the Strategy of HSV-Tk Engineering Donor Lymphocytes to Treat Patients With High Risk Acute Leukemia (TK008)

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ClinicalTrials.gov Identifier: NCT00914628
Recruitment Status : Recruiting
First Posted : June 5, 2009
Last Update Posted : September 14, 2018
Sponsor:
Information provided by (Responsible Party):
MolMed S.p.A.

Brief 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

Condition or disease Intervention/treatment Phase
Acute Leukemia (Category) Genetic: HSV-Tk Other: T-cell depleted or T-cell replete strategies Phase 3

Detailed Description:

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 170 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Leukemia

Arm Intervention/treatment
Experimental: A
HSV-TK engineering donor Lymphocytes
Genetic: HSV-Tk
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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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).

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. 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)



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)


Information from the National Library of Medicine

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


Contacts
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Contact: Fabio Ciceri, MD 0

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Locations
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United States, Illinois
Northwestern University Feinberg School of Medicine Recruiting
Chicago, Illinois, United States, 60611
Contact: Jayesh Mehta, MD         
Principal Investigator: Jayesh Mehta, MD         
United States, Missouri
Washington University Medical School Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Rizwan Romee, MD         
Principal Investigator: Rizwan Romee, MD         
United States, New Jersey
John Theurer Cancer Center at Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Michele Donato, MD         
Principal Investigator: Michele Donato, MD         
Belgium
Universitair Ziekenhuis Recruiting
Gent, Belgium
Contact: Tessa Kerre, MD         
Principal Investigator: Tessa Kerre, MD         
University Hospitals Leuven Recruiting
Leuven, Belgium, 3000
Contact: Johan Maertens, MD         
Principal Investigator: Johan Maertens, MD         
Centre Hospitalier Universitaire de Liège - Domaine Universitaire du Sart Tilman Recruiting
Liège, Belgium
Contact: Yves Beguin, MD         
Principal Investigator: Yves Beguin, MD         
France
Hôpital Jean Minjoz Recruiting
Besançon, France, 25030
Contact: Eric Deconinck, MD         
Principal Investigator: Eric Deconinck, MD         
Centre Hospitalier Universitaire de Clermont-Ferrand Recruiting
Clermont-Ferrand, France
Contact: Jacques Olivier Bay, MD         
Principal Investigator: Jacques Olivier Bay, MD         
Centre Hospitalier Régional Universitaire de Lille Recruiting
Lille, France
Contact: Ibrahim Yakoub-agha, MD         
Principal Investigator: Ibrahim Yakoub-agha, MD         
Institut Paoli-Calmettes Recruiting
Marseille, France
Contact: Didier Blaise, MD         
Principal Investigator: Didier Blaise, MD         
Centre Hospitalier Universitaire de Nantes Recruiting
Nantes, France
Contact: Patrice Chevallier, MD         
Principal Investigator: Patrice Chevallier, MD         
Hôpital l'Archet Recruiting
Nice, France
Contact: Pierre-Simon Rohrlich, MD         
Principal Investigator: Pierre-Simon Rohrlich, MD         
Hôpital Saint-Antoine Recruiting
Paris, France
Contact: Mohamad Mothy, MD         
Principal Investigator: Mohamad Mothy, MD         
IUCT Oncopole - Institut Universitaire du Cancer de Toulouse Not yet recruiting
Toulouse, France
Contact: Anne Huynh, MD         
Principal Investigator: Anne Huynh, MD         
Germany
Charitè; Campus Benjamin Franklin Recruiting
Berlin, Germany, 13353
Contact: Lutz Uharek, MD         
Principal Investigator: Lutz Uharek, MD         
University Medical Center Hamburg-Eppendorf Recruiting
Hamburg, Germany
Contact: Nicolaus Martin Kroger, MD         
Principal Investigator: Nicolaus Martin Kroger, MD         
Medizinische Hochschule Hannover Recruiting
Hannover, Germany, 30625
Contact: Arnold Ganser, MD         
Contact: Eva Mischak-Weissinger, MD         
Principal Investigator: Arnold Ganser, MD         
Sub-Investigator: Eva Mischak-Weissinger, MD         
University of Leipzig Recruiting
Leipzig, Germany, 04103
Contact: Dietger Niederwieser, MD         
Principal Investigator: Dietger Niederwieser, MD         
Universitat Tubingen Recruiting
Tubingen, Germany, 72076
Contact: Wolfgang Bethge, MD         
Principal Investigator: Wolfgang Bethge, MD         
Medizinische Klinik und Poliklinik Recruiting
Ulm, Germany, 89081
Contact: Donald Bunjes, MD         
Principal Investigator: Donald Bunjes, MD         
Greece
George Papanicolaou Hospital Recruiting
Thessaloniki, Greece, 57010
Contact: Evangelia Yannaki, MD         
Principal Investigator: Evangelia Yannaki, MD         
Israel
Chaim Sheba Medical Center Recruiting
Tel Hashomer, Israel, 52621
Contact: Arnon Nagler, MD         
Principal Investigator: Arnon Nagler, MD         
Italy
Azienda Sanitaria Ospedaliera S.Croce e Carle Recruiting
Cuneo, CN, Italy
Contact: Nicola Mordini, MD         
Principal Investigator: Nicola Mordini, MD         
Azienda Ospedaliero-Universitaria Policlinico-Vittorio Emanuele Recruiting
Catania, CT, Italy
Contact: Giuseppe Milone, MD         
Principal Investigator: Giuseppe Milone, MD         
Azienda Ospedaliera Universitaria Careggi Recruiting
Firenze, FI, Italy
Contact: Riccardo Saccardi, MD         
Principal Investigator: Riccardo Saccardi, MD         
Azienda Ospedaliera Ospedali Riuniti Villa Sofia - Cervello Not yet recruiting
Palermo, PA, Italy
Contact: Alessandro Indovina, MD         
Principal Investigator: Alessandro Indovina, MD         
Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Presidio Molinette Recruiting
Torino, TO, Italy
Contact: Benedetto Bruno, MD         
Principal Investigator: Benedetto Bruno, MD         
Ospedale Santa Maria della Misericordia Recruiting
Udine, UD, Italy
Contact: Francesca Patriarca, MD         
Principal Investigator: Francesca Patriarca, MD         
Policlinico G. B. Rossi, Azienda ospedaliera universitaria integrata di Verona Recruiting
Verona, VR, Italy
Contact: Fabio Benedetti, Md         
Principal Investigator: Fabio Benedetti, MD         
Ospedale San Raffaele Recruiting
Milan, Italy
Contact: Fabio Ciceri, MD    0      
Principal Investigator: Fabio Ciceri, MD         
Azienda Ospedaliero-Universitaria Policlinico di Modena Recruiting
Modena, Italy, 41124
Contact: Franco Narni, MD         
Principal Investigator: Franco Narni, MD         
Lithuania
Santaros Klinikos Recruiting
Vilnius, Lithuania
Contact: Valdas Pečeliūnas, MD         
Principal Investigator: Valdas Pečeliūnas, MD         
Portugal
Centro Hospitalar Lisboa Norte, E.P.E. Not yet recruiting
Lisboa, Portugal
Contact: João F. Lacerda, MD         
Principal Investigator: João F. Lacerda, MD         
Spain
Hospital de la Santa Creu i Sant Pau Recruiting
Barcelona, Spain
Contact: Jorge Sierra, MD         
Principal Investigator: Jorge Serra, MD         
Instituto Catalán de Oncología Recruiting
L'Hospitalet De Llobregat, Spain
Contact: Rocio Parodi, MD         
Principal Investigator: Rocio Parodi, MD         
Hospital de Navarra Recruiting
Pamplona, Spain, 31008
Contact: Mercedes Rodríguez, MD         
Principal Investigator: Mercedes Rodríguez, MD         
Sponsors and Collaborators
MolMed S.p.A.
Investigators
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Study Director: Antonio Lambiase, MD MolMed S.p.A.

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Responsible Party: MolMed S.p.A.
ClinicalTrials.gov Identifier: NCT00914628     History of Changes
Other Study ID Numbers: TK008
2009-012973-37 ( Registry Identifier: EUdraCT number )
First Posted: June 5, 2009    Key Record Dates
Last Update Posted: September 14, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No, only information requested by law will be released
Keywords provided by MolMed S.p.A.:
high risk acute leukemia
HSV-TK
Haploidentical HCT
GvHD
GvL
Immunoreconstitution
Additional relevant MeSH terms:
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Leukemia
Acute Disease
Neoplasms by Histologic Type
Neoplasms
Disease Attributes
Pathologic Processes