WT1 Immunity Via DNA Fusion Gene Vaccination in Haematological Malignancies by Intramuscular Injection Followed by Intramuscular Electroporation (WIN)

This study has suspended participant recruitment.
Sponsor:
Collaborators:
Imperial College Healthcare NHS Trust
Royal Devon and Exeter NHS Foundation Trust
Inovio Pharmaceuticals
Efficacy and Mechanism Evaluation ( EME ) programme
Leukemia Research Fund
Information provided by (Responsible Party):
University Hospital Southampton NHS Foundation Trust.
ClinicalTrials.gov Identifier:
NCT01334060
First received: April 11, 2011
Last updated: December 11, 2013
Last verified: December 2013
  Purpose

The study is not currently recruiting new subjects due to an interruption in funding from its sponsors. Efforts are under way to re-establish funding, however, the study is currently on-hold pending the outcome of these re-funding efforts. There have been no safety concerns identified during the study

This is an open label, single dose level, phase II study in two patient groups (CML and AML) using genetic randomisation. Consented and eligible HLA A2+ve patients will be vaccinated with two DNA vaccines and HLA A2 -ve patients will be followed up with molecular monitoring only. The objectives are to evaluate: 1) Molecular response following p.DOM-epitope DNA vaccination in patients with CML (BCR-ABL, WT1) and AML (WT1) at weeks 4, 8, 12, 16, 20 and at months 6, 12, 18 and 24. 2) Time to disease progression, 2 year survival rate (patients with AML) 3) Correlation of molecular responses with immunological responses. Primary Objective: CML: Molecular response of BCR-ABL. AML: Time to disease progression. Secondary Objective: Molecular response of WT1 transcript levels, immune responses to WT1 and DOM, Toxicity, CML-Time to disease progression, next treatment and survival, AML-2 year survival, overall survival


Condition Intervention Phase
Leukaemia (Acute)
Leukaemia (Chronic)
Leukaemia (Acute Myeloid)
Leukaemia (Acute Lymphoblastic)
Leukaemia (Acute Promyelocytic)
Biological: p.DOM-WT1-37 DNA Vaccine and p.DOM-WT1-126 DNA Vaccine
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: WT1 Immunity Via DNA Fusion Gene Vaccination in Haematological Malignancies by Intramuscular Injection Followed by Intramuscular Electroporation

Resource links provided by NLM:


Further study details as provided by University Hospital Southampton NHS Foundation Trust.:

Primary Outcome Measures:
  • Molecular response following p.DOM-epitope DNA vaccination in patients with CML (BCR-ABL, WT1) and AML (WT1) [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • CML-Time to disease progression, next treatment and survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • AML-2 year survival, overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 184
Study Start Date: February 2010
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: CML HLA A2-
No Intervention: AML HLA A2-
Experimental: AML HLA A2+ Biological: p.DOM-WT1-37 DNA Vaccine and p.DOM-WT1-126 DNA Vaccine
p.DOM-WT1-37: 1mg/dose/vaccine p.DOM-WT1-126: 1mg/dose/vaccine The DNA vaccine will be administered 6 times at 4 weekly intervals. Responders (Immunological but without molecular progression) may continue vaccination 3 monthly to maximum of 24 months. The vaccines will be injected intramuscularly (im) followed by electroporation (EP) into separate locations.
Experimental: CML HLA A2+ Biological: p.DOM-WT1-37 DNA Vaccine and p.DOM-WT1-126 DNA Vaccine
p.DOM-WT1-37: 1mg/dose/vaccine p.DOM-WT1-126: 1mg/dose/vaccine The DNA vaccine will be administered 6 times at 4 weekly intervals. Responders (Immunological but without molecular progression) may continue vaccination 3 monthly to maximum of 24 months. The vaccines will be injected intramuscularly (im) followed by electroporation (EP) into separate locations.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • CML patients:

Philadelphia chromosome positive CML in chronic phase, in complete cytogenetic response (CCyR) but with detectable BCR-ABL transcripts and maintained the CCyR on imatinib monotherapy for a minimum of 24 months

AML patients:

WT1+ AML in CR or morphologic CR with incomplete blood count recovery (CRi);

All patients:

  • ≥ 18 years of age, written informed consent
  • Performance status of 0 or 1.
  • for vaccination groups: HLA-A0201 positive in at least one allele
  • for control groups: HLA A2 negative in both alleles
  • renal function and liver function (Creatinine <1.5 x upper limit of normal, liver function tests < 1.5 x upper limit of normal); Lymphocyte count > 1.0 x109/l; normal clotting
  • HB>100 g/l
  • Adequate venous access for repeated blood sampling according to protocol schedule.
  • If sexually active and possibly fertile, patients must agree to use appropriate contraceptive methods during the trial and for six months afterwards.

Exclusion Criteria:

  • CML patients:

    • CML in accelerated phase or blast crisis or having achieved CMR at any point during imatinib therapy.
    • Imatinib dose modification in the previous year, Imatinib interruption for more than 15 days in the previous 6 months to enrolment
    • Prior interferon-α therapy
    • hypocellular bone marrow (<20%)
    • Complete molecular response (CMR)

AML patients:

  • AML in haematological relapse or eligible for allogeneic SCT.
  • hypocellular bone marrow (<20%)
  • AML patients with the "good-risk" abnormalities comprised by the core binding factor leukaemias (i.e., AML with the translocation (8;21) and inversion of chromosome 16, and acute promyelocytic leukaemia with the translocation (15;17))

All patients:

  • Systemic steroids or other drugs with a likely effect on immune competence are forbidden during the trial. The predictable need of their use will preclude the patient from trial entry
  • Major surgery in the preceding three to four weeks from which the patient has not yet recovered.
  • Patients who are of high medical risk because of non-malignant systemic disease, as well as those with active uncontrolled infection.
  • Patients with any other condition which in the Investigator's opinion would not make the patient a good candidate for the clinical trial, such as concurrent congestive heart failure or prior history of New York Heart Association (NYHA) class III/ IV cardiac disease
  • Current malignancies at other sites, with the exception of adequately treated basal or squamous cell carcinoma of the skin. Cancer survivors, who have undergone potentially curative therapy for a prior malignancy, have no evidence of that disease for five years and are deemed at low risk for recurrence, are eligible for the study.
  • Patients who are serologically positive for or are known to suffer from Hepatitis B, C, Syphilis or HIV. Counselling will be offered to all patients prior to testing.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01334060

Locations
United Kingdom
Royal Devon and Exeter NHS Foundation Trust
Exeter, United Kingdom, EX2 5DW
Imperial College NHS Trust
London, United Kingdom, W12 0HS
Southampton University Hospitals NHS Trust
Southampton, United Kingdom, SO16 6YD
Sponsors and Collaborators
University Hospital Southampton NHS Foundation Trust.
Imperial College Healthcare NHS Trust
Royal Devon and Exeter NHS Foundation Trust
Inovio Pharmaceuticals
Efficacy and Mechanism Evaluation ( EME ) programme
Leukemia Research Fund
  More Information

Publications:
Responsible Party: University Hospital Southampton NHS Foundation Trust.
ClinicalTrials.gov Identifier: NCT01334060     History of Changes
Other Study ID Numbers: RHMCAN0700, 2009-017340-14, ISRCTN62678383
Study First Received: April 11, 2011
Last Updated: December 11, 2013
Health Authority: United Kingdom: Department of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Leukemia
Hematologic Neoplasms
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Hematologic Diseases

ClinicalTrials.gov processed this record on September 18, 2014