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Hematological MalignanciesPhase 1/2NCT00423124

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

A Phase 1/2 study testing HSV-TK in people with Hematological Malignancies, run by AGC Biologics S.p.A. at 8 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hematological Malignancies
What is being tested?
HSV-TK
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
57 participants
Where
8 sitesin 5 countries
Study dates
Jul 2002to Nov 2013
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 14Show fewer
  • 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

Who cannot join

  • 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
Show all 9Show fewer
  • Life-threatening condition or complication other than their basic disease
  • CNS disease
  • Pregnant or lactating women

Trial locations and contacts

8 sites in 5 countries.

8 sites in 5 countries

Italy4 sites

  • Fondazione San Raffaele

    Milan

  • Istituto Clinico Humanitas

    Milan

  • Policlinico Monteluce

    Perugia

  • Ospedale Civile

    Pescara

Other trials in Italy

Germany1 site

  • Medizinische Hoschule Hannover

    Hanover

Other trials in Germany

Greece1 site

  • G. Papanicolau

    Thessaloniki

Other trials in Greece

Israel1 site

  • Hadassah University Hospital

    Jerusalem

Other trials in Israel

United Kingdom1 site

  • Hammersmith Hospital

    London

Other trials in United Kingdom

About this study

Official title: A Phase I-II Study: Infusion of Donor Lymphocytes Transduced With the Suicide Gene HSV TK, After Transplantation of Allogeneic T-depleted Stem Cells From a Haploidentical Donor in Patients With Haematological Malignancies

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.

Read the 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 CD4+ reconstitution could take more than 10 months. The low number of lymphocytes infused with the graft, the degree of HLA 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 haplo-HCT, because it remarkably may enhance both GvL 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, eventually, survival in patients receiving haplo-HCT. Finally, this therapeutic approach, which allows the safe infusion of escalating doses of donor lymphocytes, 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 hematological malignancies, who have undergone haploidentical stem cell transplantation.

Being tested
HSV-TK
Keywords
Hematological malignancies, HSV-TK, Haploidentical HCT, GvHD, GvL
Medical subject headings
Hematologic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • HSV-TKGenetic

    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.

Study groups in NCT00423124
Study groupRoleWhat they receive
AExperimentalNot described
Receives: Genetic: HSV-TK

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: during the study

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

    Measured: during the study

  3. Evaluation of GvL effect

    Measured: during the study

Secondary outcomes (3)

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

    Measured: during the study

  2. Incidence of infectious events (measured by number of infectious events)

    Measured: during the study

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

    Measured: during the study and study follow up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Jan 2007 (estimated)
  2. Study startJul 2002
  3. Primary completionDec 2011
  4. Study completionNov 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
57 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00423124
Sponsor's protocol ID
TK007
Other IDs
2005-003587-34, 2005
Status last verified
May 2014
First submitted
16 Jan 2007
Last updated
30 May 2014
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 19345145

  • 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.

    PubMed 33554732

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing HSV-TK in people with Hematological Malignancies, run by AGC Biologics S.p.A. at 8 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 May 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Italy, Germany, Greece, Israel, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Evaluation of clinical activity in terms of immune-reconstitution, provided by the add- back of the transduced T-cells after haplo-HCT (time frame: during the study). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00423124, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 May 2014.

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