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

NCT00914628 | Terminated Phase 3 Results

• 2 other identifiers: TK0082009-012973-37
• Study Type: interventional
• Target: 92
• Locations: 10 countries
• Sites: 36

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

Conditions

Acute Leukemia (Category)

Keywords

high risk acute leukemia; HSV-TK; Haploidentical HCT; GvHD; GvL; Immunoreconstitution

Outcome Measures

Primary Outcomes (1)

• Disease-free Survival (DFS)

  Defined as the measure from the date of randomization until the date of relapse (or progression), or death from any cause, whichever occurs first. Disease relapse or progression was determined by the Investigator based on the following disease examination: * Morphology (bone marrow or peripheral blood) * Confirmation of mixed or full chimerism (evaluation of the degree of chimerism between donor/host, according to institutional clinical practice, on bone marrow or peripheral blood) * Cytogenetic and/or molecular and/or other tests, according to institutional clinical practice (bone marrow or peripheral blood).

  From the date of randomization, assessed up to 12 months

Secondary Outcomes (11)

• Overall Survival (OS)

  From the date of randomization to the date of death, assessed up to 12 months

• Immune Reconstitution (IR)

  Weekly up to IR after engraftment of HCT, monthly for 6 months from date of IR and then at month 9 and 12

• Engraftment Rate

  At day 15 after HCT, monthly for 6 months after HCT and then at month 9 and 12

• Cumulative Incidence of Grade 2, 3, or 4 Acute GvHD (aGvHD)

  from the date of HCT until the date of the first occurrence of aGvHD, assessed up to 6 months

• Cumulative Incidence of Chronic GvHD (cGvHD)

  From the date of HCT until the date of the first occurrence of cGvHD, assessed up to 12 months

Study Arms (2)

A

EXPERIMENTAL

HSV-TK engineering donor Lymphocytes

Genetic: HSV-Tk

B

ACTIVE COMPARATOR

T-cell depleted or T-cell replete strategies

Other: T-cell depleted or T-cell replete strategies

Interventions

HSV-Tk GENETIC

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.

A

T-cell depleted or T-cell replete strategies OTHER

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

B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Any of the following conditions:
• AML and ALL in 1st complete remission (CR1)
• AML and ALL in 2nd or subsequent CR
• secondary AML in CR
• 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

You may not qualify if:

• 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.
• 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)

Sponsors & Collaborators

• AGC Biologics S.p.A.: lead

Study Sites (36)

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

Washington University Medical School

St Louis, Missouri, 63110, United States

Location

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Universitair Ziekenhuis

Ghent, Belgium

Location

University Hospitals Leuven

Leuven, 3000, Belgium

Location

Centre Hospitalier Universitaire de Liège - Domaine Universitaire du Sart Tilman

Liège, Belgium

Location

Hôpital Jean Minjoz

Besançon, 25030, France

Location

Centre Hospitalier Universitaire de Clermont-Ferrand

Clermont-Ferrand, France

Location

Centre Hospitalier Régional Universitaire de Lille

Lille, France

Location

Institut Paoli-Calmettes

Marseille, France

Location

Centre Hospitalier Universitaire de Nantes

Nantes, France

Location

Hôpital l'Archet

Nice, France

Location

Hôpital Saint-Antoine

Paris, France

Location

IUCT Oncopole - Institut Universitaire du Cancer de Toulouse

Toulouse, France

Location

Charitè; Campus Benjamin Franklin

Berlin, 13353, Germany

Location

University Medical Center Hamburg-Eppendorf

Hamburg, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

University of Leipzig

Leipzig, 04103, Germany

Location

Universitat Tubingen

Tübingen, 72076, Germany

Location

Medizinische Klinik und Poliklinik

Ulm, 89081, Germany

Location

George Papanicolaou Hospital

Thessaloniki, 57010, Greece

Location

Chaim Sheba Medical Center

Tel Litwinsky, 52621, Israel

Location

Azienda Sanitaria Ospedaliera S.Croce e Carle

Cuneo, CN, Italy

Location

Azienda Ospedaliero-Universitaria Policlinico-Vittorio Emanuele

Catania, CT, Italy

Location

Azienda Ospedaliera Universitaria Careggi

Florence, FI, Italy

Location

Azienda Ospedaliera Ospedali Riuniti Villa Sofia - Cervello

Palermo, PA, Italy

Location

Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Presidio Molinette

Torino, TO, Italy

Location

Ospedale Santa Maria della Misericordia

Udine, UD, Italy

Location

Policlinico G. B. Rossi, Azienda ospedaliera universitaria integrata di Verona

Verona, VR, Italy

Location

Ospedale San Raffaele

Milan, Italy

Location

Azienda Ospedaliero-Universitaria Policlinico di Modena

Modena, 41124, Italy

Location

Santaros Klinikos

Vilnius, Lithuania

Location

Centro Hospitalar Lisboa Norte, E.P.E.

Lisbon, Portugal

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

Location

Instituto Catalán de Oncología

L'Hospitalet de Llobregat, Spain

Location

Hospital de Navarra

Pamplona, 31008, Spain

Location

Results Point of Contact

• Title: Anna Stornaiuolo
• Organization: AGC Biologics S.p.A

astornaiuolo@agcbio.com

00390221277440

Study Officials

• Antonio Lambiase, MD

  AGC Biologics S.p.A.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2009
• First Posted: June 5, 2009
• Study Start: April 12, 2010
• Primary Completion: November 30, 2019
• Study Completion: November 30, 2019
• Last Updated: June 22, 2021
• Results First Posted: June 22, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

FR (8); LI (1); PT (1); GR (1); ES (3); BE (3); IT (9); US (3); DE (6); IL (1)