Leukaemia (Acute)Phase 2WINNCT01334060
WT1 Immunity Via DNA Fusion Gene Vaccination in Haematological Malignancies by Intramuscular Injection Followed by Intramuscular Electroporation
A Phase 2 study testing p.DOM-WT1-37 DNA Vaccine and p.DOM-WT1-126 DNA Vaccine in people with Leukaemia (Acute) and Leukaemia (Chronic), run by University Hospital Southampton NHS Foundation Trust at 3 sites in United Kingdom.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukaemia (Acute), Leukaemia (Chronic), Leukaemia (Acute Myeloid)
- What is being tested?
- p.DOM-WT1-37 DNA Vaccine and p.DOM-WT1-126 DNA Vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- 1 Feb 2011to 26 Feb 2013
- Phase
- Phase 2
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
- 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
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- 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.
Who cannot join
- 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)
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- 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.
Trial locations and contacts
3 sites in 1 country.
United Kingdom3 sites
Royal Devon and Exeter NHS Foundation Trust
Exeter, EX2 5DW
Imperial College NHS Trust
London, W12 0HS
Southampton University Hospitals NHS Trust
Southampton, SO16 6YD
About this study
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
- Conditions
- Leukaemia (Acute), Leukaemia (Chronic), Leukaemia (Acute Myeloid), Leukaemia (Acute Lymphoblastic), Leukaemia (Acute Promyelocytic)
- Being tested
- p.DOM-WT1-37 DNA Vaccine and p.DOM-WT1-126 DNA Vaccine
- Medical subject headings
- Leukemia, Bronchiolitis Obliterans Syndrome, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
p.DOM-WT1-37 DNA Vaccine and p.DOM-WT1-126 DNA VaccineBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| CML HLA A2- | No intervention | Not described |
| AML HLA A2- | No intervention | Not described |
| AML HLA A2+ | Experimental | Not described Receives: Biological: p.DOM-WT1-37 DNA Vaccine and p.DOM-WT1-126 DNA Vaccine |
| CML HLA A2+ | Experimental | Not described Receives: Biological: p.DOM-WT1-37 DNA Vaccine and p.DOM-WT1-126 DNA Vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Molecular response following p.DOM-epitope DNA vaccination in patients with CML (BCR-ABL, WT1) and AML (WT1)
Measured: 2 years
Secondary outcomes (2)
CML-Time to disease progression, next treatment and survival
Measured: 2 years
AML-2 year survival, overall survival
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2011 (estimated)
- Study start1 Feb 2011
- Primary completionFeb 2013
- Study completion26 Feb 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Leukaemia (Acute)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Southampton NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Imperial College Healthcare NHS Trust, Royal Devon and Exeter NHS Foundation Trust, Inovio Pharmaceuticals, Efficacy and Mechanism Evaluation (EME) Programme, Leukemia Research Fund
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01334060
- Sponsor's protocol ID
- RHMCAN0700
- Other IDs
- 2009-017340-14, ISRCTN62678383, 2009
- Acronym
- WIN
- Status last verified
- Sep 2018
- First submitted
- 11 Apr 2011
- Last updated
- 7 Sep 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Chaise C, Buchan SL, Rice J, Marquet J, Rouard H, Kuentz M, Vittes GE, Molinier-Frenkel V, Farcet JP, Stauss HJ, Delfau-Larue MH, Stevenson FK. DNA vaccination induces WT1-specific T-cell responses with potential clinical relevance. Blood. 2008 Oct 1;112(7):2956-64. doi: 10.1182/blood-2008-02-137695. Epub 2008 May 23.
PubMed 18502835Rice J, Ottensmeier CH, Stevenson FK. DNA vaccines: precision tools for activating effective immunity against cancer. Nat Rev Cancer. 2008 Feb;8(2):108-20. doi: 10.1038/nrc2326.
PubMed 18219306