Infusion of Donor Lymphocytes Transduced With the Suicide Gene HSV TK in Patients With Haematological Malignancies

NCT00423124 | Completed Phase 1

• 2 other identifiers: TK0072005-003587-34
• Study Type: interventional
• Target: 57
• Locations: 5 countries
• Sites: 8

Brief Summary

The aim of the study is to obtain immune reconsitutuion as well as reduction of infective episodes and disease relapse in patient with haematological malignancies who underwent SCT(and subsequent T lymphocytes infusions) and selectively controlling GvHD.

Conditions

Hematological Malignancies

Keywords

Hematological malignancies; HSV-TK; Haploidentical HCT; GvHD; GvL

Outcome Measures

Primary Outcomes (3)

• Evaluation of clinical activity in terms of immune-reconstitution, provided by the add- back of the transduced T-cells after haplo-HCT

  during the study

• Evaluation of the "in vivo" control of GvHD after administration of ganciclovir in patients treated with HSV-TK transduced T-cells

  during the study

• Evaluation of GvL effect

  during the study

Secondary Outcomes (3)

• Time to relapse, time to death (evaluated by disease free survival and overall survival)

  during the study

• Incidence of infectious events (measured by number of infectious events)

  during the study

• Acute and long term toxicity related to the infusions (measured by incidence of adverse events)

  during the study and study follow up

Study Arms (1)

A

EXPERIMENTAL

Genetic: HSV-TK

Interventions

HSV-TK GENETIC

Infusion of genetically modified lymphocytes (1x10\^6-1x10\^7 c/kg): first at +21-+49 days after HSCT; in absence of immune reconstitution and GvHD further infusions up to 4 will be administered on monthly basis.

A

Eligibility Criteria

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

You may qualify if:

• Patients \>=18 years old affected by hematological malignancies at high risk of relapse based on disease progression or presence of negative prognostic factors, who have received a HCT from donor HLA mismatched (haploidentical) for 2 or 3 loci
• Engraftment documented by \>500 neutrophils/µl for three consecutive days in the absence of growth factors
• Mixed chimerism or full donor chimerism confirmed
• AML in 1st or 2nd relapse or primary refractory
• High-risk AML in 1st or subsequent remission
• RAEB and RAEB-T
• CML in 2nd chronic phase, blast crisis or accelerated phase
• Poor prognosis ALL in 1st or subsequent remission
• High grade lymphomas in 3rd or subsequent remission
• Multiple myeloma in advanced stage relapsing or progressing after high dose chemotherapy
• Absence of fully HLA matched or one HLA locus mismatched family donor
• Stable clinical conditions and life expectancy \>3 months
• PS Karnofsky \>70
• Written donor/patient informed consent

You may not qualify if:

• Infection with cytomegalovirus being treated with ganciclovir
• Presence of GvHD grade \> I that requires systemic immunosuppressive therapy (at baseline)
• Ongoing systemic immunosuppressive therapy
• Ongoing acyclovir administration
• Administration after haplo-HCT of G-CSF and cyclosporine A
• CD3+ lymphocytes \>100/µl before day +42 after haplo-HCT
• Life-threatening condition or complication other than their basic disease
• CNS disease
• Pregnant or lactating women

Sponsors & Collaborators

• AGC Biologics S.p.A.: lead

Study Sites (8)

Medizinische Hoschule Hannover

Hanover, Germany

Location

G. Papanicolau

Thessaloniki, Greece

Location

Hadassah University Hospital

Jerusalem, Israel

Location

Fondazione San Raffaele

Milan, Italy

Location

Istituto Clinico Humanitas

Milan, Italy

Location

Policlinico Monteluce

Perugia, Italy

Location

Ospedale Civile

Pescara, Italy

Location

Hammersmith Hospital

London, United Kingdom

Location

Related Publications (2)

• Ciceri F, Bonini C, Stanghellini MT, Bondanza A, Traversari C, Salomoni M, Turchetto L, Colombi S, Bernardi M, Peccatori J, Pescarollo A, Servida P, Magnani Z, Perna SK, Valtolina V, Crippa F, Callegaro L, Spoldi E, Crocchiolo R, Fleischhauer K, Ponzoni M, Vago L, Rossini S, Santoro A, Todisco E, Apperley J, Olavarria E, Slavin S, Weissinger EM, Ganser A, Stadler M, Yannaki E, Fassas A, Anagnostopoulos A, Bregni M, Stampino CG, Bruzzi P, Bordignon C. Infusion of suicide-gene-engineered donor lymphocytes after family haploidentical haemopoietic stem-cell transplantation for leukaemia (the TK007 trial): a non-randomised phase I-II study. Lancet Oncol. 2009 May;10(5):489-500. doi: 10.1016/S1470-2045(09)70074-9. Epub 2009 Apr 1.

  PMID: 19345145 RESULT

• Stornaiuolo A, Valentinis B, Sirini C, Scavullo C, Asperti C, Zhou D, Martinez De La Torre Y, Corna S, Casucci M, Porcellini S, Traversari C. Characterization and Functional Analysis of CD44v6.CAR T Cells Endowed with a New Low-Affinity Nerve Growth Factor Receptor-Based Spacer. Hum Gene Ther. 2021 Jul;32(13-14):744-760. doi: 10.1089/hum.2020.216. Epub 2021 May 5.

  PMID: 33554732 DERIVED

MeSH Terms

Conditions

Hematologic Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Fabio Ciceri, MD

  Hematology and BMT Unit, San Raffaele Scientific Institute, Milan, Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2007
• First Posted: January 17, 2007
• Study Start: July 1, 2002
• Primary Completion: December 1, 2011
• Study Completion: November 1, 2013
• Last Updated: May 30, 2014

Record last verified: 2014-05

Locations

IT (4); GB (1); GR (1); DE (1); IL (1)