NCT01334060

Brief 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. 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

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
23

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Feb 2011

Geographic Reach
1 country

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2011

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

April 11, 2011

Completed
1 day until next milestone

First Posted

Study publicly available on registry

April 12, 2011

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2013

Completed
25 days until next milestone

Study Completion

Last participant's last visit for all outcomes

February 26, 2013

Completed
Last Updated

September 7, 2018

Status Verified

September 1, 2018

Enrollment Period

2 years

First QC Date

April 11, 2011

Last Update Submit

September 5, 2018

Conditions

Leukaemia (Acute)Leukaemia (Chronic)Leukaemia (Acute Myeloid)Leukaemia (Acute Lymphoblastic)Leukaemia (Acute Promyelocytic)

Outcome Measures

Primary Outcomes (1)

  • Molecular response following p.DOM-epitope DNA vaccination in patients with CML (BCR-ABL, WT1) and AML (WT1)

    2 years

Secondary Outcomes (2)

  • CML-Time to disease progression, next treatment and survival

    2 years

  • AML-2 year survival, overall survival

    2 years

Study Arms (4)

CML HLA A2-

NO INTERVENTION

AML HLA A2-

NO INTERVENTION

AML HLA A2+

EXPERIMENTAL
Biological: p.DOM-WT1-37 DNA Vaccine and p.DOM-WT1-126 DNA Vaccine

CML HLA A2+

EXPERIMENTAL
Biological: p.DOM-WT1-37 DNA Vaccine and p.DOM-WT1-126 DNA Vaccine

Interventions

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.

AML HLA A2+CML HLA A2+

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Royal Devon and Exeter NHS Foundation Trust

Exeter, EX2 5DW, United Kingdom

Location

Imperial College NHS Trust

London, W12 0HS, United Kingdom

Location

Southampton University Hospitals NHS Trust

Southampton, SO16 6YD, United Kingdom

Location

Related Publications (2)

  • 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.

    PMID: 18502835RESULT

  • Rice 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.

    PMID: 18219306RESULT

MeSH Terms

Conditions

LeukemiaBronchiolitis Obliterans SyndromeLeukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesOrganizing PneumoniaBronchiolitis ObliteransBronchiolitisBronchitisBronchial DiseasesRespiratory Tract DiseasesLung Diseases, ObstructiveLung DiseasesGraft vs Host DiseaseImmune System DiseasesLeukemia, Myeloid

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 11, 2011

First Posted

April 12, 2011

Study Start

February 1, 2011

Primary Completion

February 1, 2013

Study Completion

February 26, 2013

Last Updated

September 7, 2018

Record last verified: 2018-09

Locations

GB(3)