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Trial registered on ANZCTR


Registration number
ACTRN12612000800820
Ethics application status
Approved
Date submitted
23/07/2012
Date registered
31/07/2012
Date last updated
2/08/2012
Type of registration
Prospectively registered

Titles & IDs
Public title
Combined Infusion of Immune Cells and Vaccination to Boost Immunity to Infection After Bone Marrow Transplantation
Scientific title
In haemopoietic stem cell transplant patients, does infusion of infection-specific T-cells combined with vaccination (compared to no vaccination) enhance immune reconstitution safely?
Secondary ID [1] 280890 0
Nil
Universal Trial Number (UTN)
U1111-1132-8656
Trial acronym
CynTax Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Post haemopoietic stem cell transplant infection 286963 0
Condition category
Condition code
Infection 287300 287300 0 0
Other infectious diseases
Cancer 287340 287340 0 0
Leukaemia - Acute leukaemia
Cancer 287341 287341 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Donor derived infection-specific T-cells (with activity against CMV, Adenovirus, EBV, VZV, Influenza, BKV and Aspergillus), 2x10^7 cells/m^2 intravenously after day+28 post transplant;
and vaccination (with Fluvax and Varivax), 0.5ml each by subcutaneous injection 24-72 hours post T-cell infusion.

3 SEQUENTIAL groups, each compared to historical controls.
1) 6 patients receiving multi-infection specific T-cells alone
2) 6 patients receiving multi-infection specific T-cells plus Fluvax
3) 6 patients receiving multi-infection specific T-cells plus Fluvax and Varivax
Intervention code [1] 285323 0
Treatment: Other
Intervention code [2] 285358 0
Prevention
Comparator / control treatment
Donor derived infection-specific T-cells alone administered to 50 haemopoietic stem cell transplant recipients at Westmead Hospital and Childrens Hospital Westmead between 2003 and 2011
Control group
Historical

Outcomes
Primary outcome [1] 287577 0
Safety of infection-specific T-cell infusion and vaccination

Acutely- pulse, BP, Oxygen saturation and respiratory rate every 30 minutes for 2 hours post T-cell infusion.
Thereafter assessed clinically with history and physical examination and with full blood count, renal and liver function tests. Adverse events graded according to the NCI common toxicity criteria.
Timepoint [1] 287577 0
1 week, 2 weeks, 3 weeks 4 weeks, 3 months, 6 months, 9 months, 12 months
(post T-cell infusion)
Secondary outcome [1] 298433 0
Infection specific immune reconstitution.
Assessed by response to viral and fungal antigens by ELISPOT or cytokine flow cytometry.
Timepoint [1] 298433 0
1 week, 2 weeks, 3 weeks 4 weeks, 3 months, 6 months, 9 months, 12 months
(post T-cell infusion)
Secondary outcome [2] 298434 0
Incidence of CMV, AdV, EBV, VZV, Influenza, BKV and Aspergillus reactivation and infection.
Assessed by weekly PCR for CMV and EBV, clinically for signs of infection and further testing as indicated (eg immunofluorescence and PCR for other pathogens) on blood, urine and tissue samples.
Timepoint [2] 298434 0
1 week, 2 weeks, 3 weeks 4 weeks, 3 months, 6 months, 9 months, 12 months
(post T-cell infusion)
Secondary outcome [3] 298435 0
CMV, EBV and BKV load based on quantitative PCR
Timepoint [3] 298435 0
1 week, 2 weeks, 3 weeks 4 weeks, 3 months, 6 months, 9 months, 12 months
(post T-cell infusion)
Secondary outcome [4] 298436 0
Use of specific anti-viral pharmacotherapy
Timepoint [4] 298436 0
1 week, 2 weeks, 3 weeks 4 weeks, 3 months, 6 months, 9 months, 12 months
(post T-cell infusion)
Secondary outcome [5] 298437 0
Use of systemic anti-fungal drugs including amphotericin and azoles
Timepoint [5] 298437 0
1 week, 2 weeks, 3 weeks 4 weeks, 3 months, 6 months, 9 months, 12 months
(post T-cell infusion)
Secondary outcome [6] 298438 0
Incidence of acute and chronic GVHD.
Assessed by history and physical examination and tissue confirmation (eg gastric or skin biopsy) in patients with symptoms or signs of GVHD.
Timepoint [6] 298438 0
1 week, 2 weeks, 3 weeks 4 weeks, 3 months, 6 months, 9 months, 12 months
(post T-cell infusion)
Secondary outcome [7] 298439 0
Number of in-hospital days following first discharge post transplant
Timepoint [7] 298439 0
1 week, 2 weeks, 3 weeks 4 weeks, 3 months, 6 months, 9 months, 12 months
(post T-cell infusion)

Eligibility
Key inclusion criteria
1. Patients undergoing myeloablative or non-myeloablative allogeneic transplantation from an HLA (A, B and DR) identical or 1-3 antigen mismatched family or unrelated donor.
2. Transplant performed for any type of non-malignant condition or haematological malignancy including but not limited to acute and chronic leukaemia, myelodysplasia, non Hodkgins and Hodgkins lymphoma or myeloma.
3. Recipients of peripheral blood or bone marrow stem cells.
4. Adequate hepatic and renal function (< 3 x upper limit of normal for AST (SGOT), ALT (SGPT), < 2 x upper limit of normal for total bilirubin, serum creatinine).
5. Estimated life expectancy of at least 6 months.
6. Patient (or legal representative) has given informed consent.
Minimum age
No limit
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Use of anti-lymphocyte globulin (ALG, ATG, Campath or other broad spectrum lymphocyte antibody) given in the 4 weeks immediately prior to infusion or planned within 4 weeks after infusion.
2. Grade II or greater graft versus host disease within 1 week prior to infusion.
3. Prednisone or methylprednisone at a dose of > 1 mg/kg (or equivalent in other steroid preparations) administered within 72 hours prior to cell infusion.
4. Allergies to eggs or components of the Fluvax or Varivax vaccines.

Study design
Purpose of the study
Prevention
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allogeneic donor recipient pairs fulfilling inclusion criteria for the trial will be identified at planning meetings of the Blood and Marrow Transplant Unit of Westmead Hospital or Children’s Hospital Westmead. Donors and recipients will be approached by the principal investigator or by associate investigators working on the Blood and Marrow Transplant Unit who will explain the purposes and procedures of the trial. For unrelated donors, a request for consent will be made through the Australian Bone Marrow Donor Registry or via overseas registries once appropriate approvals have been obtained. Once donors and patients have received information sheets and given informed consent, the transplant will be registered on the trial and the following details will be recorded by the Clinical Trials Unit of the Haematology Department of Westmead Hospital: Westmead Hospital unique patient number (UPN) of recipient, donor and recipient age, donor and recipient viral serostatus, recipient diagnosis, planned conditioning therapy.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Non-randomised
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
3 SEQUENTIAL groups, each compared to historical controls.
1) 6 patients receiving multi-infection specific T-cells alone
2) 6 patients receiving multi-infection specific T-cells plus Fluvax
3) 6 patients receiving multi-infection specific T-cells plus Fluvax and Varivax
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/08/2012
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
18
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 285679 0
Self funded/Unfunded
Name [1] 285679 0
Country [1] 285679 0
Primary sponsor type
Individual
Name
Professor DJ Gottlieb
Address
Department of Medicine,
Westmead Hospital,
Hawkesbury Rd, Westmead,
Sydney, NSW 2145
Country
Australia
Secondary sponsor category [1] 284508 0
None
Name [1] 284508 0
Address [1] 284508 0
Country [1] 284508 0
Other collaborator category [1] 276959 0
Individual
Name [1] 276959 0
Associate Professor P. Shaw
Address [1] 276959 0
Oncology Unit
Children's Hospital Westmead
Cnr Hawkesbury Rd and Hainsworth St, Westmead,
Sydney, NSW 2145
Country [1] 276959 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287667 0
Western Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 287667 0
Research Office, Room1072 Education Block
Level 1 Westmead Hospital
Hawkesbury Rd
Westmead, NSW 2145
Ethics committee country [1] 287667 0
Australia
Date submitted for ethics approval [1] 287667 0
Approval date [1] 287667 0
09/05/2012
Ethics approval number [1] 287667 0
HREC/11/WMEAD/298

Summary
Brief summary
This study aims to assess the safety and efficacy of combined infusion of immune cells and vaccination to boost immunity to infection after bone marrow transplantation.

Who is it for?
You may be eligible to join this study if you are undergoing bone marrow transplantation for any type of non-malignant condition or haematological malignancy including but not limited to acute and chronic leukaemia, myelodysplasia, non Hodgkins and Hodgkins lymphoma or myeloma.

Trial details
Participants in this trial will be allocated to one of three groups. The first group will receive multi-infection specific T-cells intravenously (via the vein) 28 days after bone marrow transplantation. The second group will also receive this treatment in addition to the Fluvax vaccination. The third group will undergo the immune cell infusion, Fluvax vaccination and Varivax vaccination.

All participants will be assessed regularly over a period of 12 months in order to determine the safety of this treatment, and to determine whether it can prevent viral and fungal infection following allogeneic blood or marrow stem cell transplantation.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34470 0
Address 34470 0
Country 34470 0
Phone 34470 0
Fax 34470 0
Email 34470 0
Contact person for public queries
Name 17717 0
Professor DJ Gottlieb
Address 17717 0
Department of Medicine,
Westmead Hospital,
Hawkesbury Rd, Westmead,
Sydney, NSW 2145
Country 17717 0
Australia
Phone 17717 0
+612-9845-6033
Fax 17717 0
+612-9687-2331
Email 17717 0
[email protected]
Contact person for scientific queries
Name 8645 0
Professor DJ Gottlieb
Address 8645 0
Department of Medicine,
Westmead Hospital,
Hawkesbury Rd, Westmead,
Sydney, NSW 2145
Country 8645 0
Australia
Phone 8645 0
+612-9845-6033
Fax 8645 0
+612-9687-2331
Email 8645 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.