Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01716364




Registration number
NCT01716364
Ethics application status
Date submitted
25/10/2012
Date registered
29/10/2012
Date last updated
4/12/2012

Titles & IDs
Public title
Safety Study of Anti LewisY Chimeric Antigen Receptor in Myeloma, Acute Myeloid Leukemia or Myelodysplastic Syndrome
Scientific title
A Phase I Study Investigating Safety Immunological Effects of Peripheral Blood T Lymphocytes Transduced With Anti LewisY Chimeric Receptor Gene in LewisY Positive Myeloma, Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome
Secondary ID [1] 0 0
LeYPh1
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 0 0
Acute Myeloid Leukaemia 0 0
Myelodysplastic Syndrome 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Cancer 0 0 0 0
Other cancer types
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Anti-LeY- scFv-CD28-? vector,.

Experimental: Anti-LeY- scFv-CD28-? vector. - Anti-LeY- scFv-CD28-? vector, a non-pathogenic, replication-incompetent retroviral vector specifically designed for this study and produced by EUFETS under GMP-conditions.


Other interventions: Anti-LeY- scFv-CD28-? vector,.
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with adverse events.
Timepoint [1] 0 0
Up to 3 years
Secondary outcome [1] 0 0
Percentage of infused labelled cells localizing in bone marrow
Timepoint [1] 0 0
Up to 3 years
Secondary outcome [2] 0 0
Percentage of infused labelled cells localizing in soft tissue or plasmacytoma.
Timepoint [2] 0 0
Up to 3 years
Secondary outcome [3] 0 0
Presence or absence of anti-LeY positive T-cells in peripheral blood and bone marrow.
Timepoint [3] 0 0
Up to 3 years
Secondary outcome [4] 0 0
Percentage of anti LeY positive T-cells in peripheral blood and bone marrow.
Timepoint [4] 0 0
Up to 3 years
Secondary outcome [5] 0 0
Serum IFN-? and IL-2 levels.
Timepoint [5] 0 0
Up to 3 years
Secondary outcome [6] 0 0
Presence or absence of autoimmune disease.
Timepoint [6] 0 0
Up to 3 years
Secondary outcome [7] 0 0
Overall response.
Timepoint [7] 0 0
Up to 3 years
Secondary outcome [8] 0 0
Time to progression
Timepoint [8] 0 0
Up to 3 years
Secondary outcome [9] 0 0
Time to treatment failure
Timepoint [9] 0 0
Up to 3 years
Secondary outcome [10] 0 0
Duration of response
Timepoint [10] 0 0
Up to 3 years
Secondary outcome [11] 0 0
Overall survival
Timepoint [11] 0 0
Up to 3 years
Secondary outcome [12] 0 0
Location of labelled re-infused T-cells
Timepoint [12] 0 0
Up to 1 month
Secondary outcome [13] 0 0
LewisY expression assessed with Flow Cytometry in Peripheral Blood and Bone Marrow.
Timepoint [13] 0 0
Up to 3 years
Secondary outcome [14] 0 0
LewisY expression assessed with Flow Cytometry in Peripheral Blood and Bone
Timepoint [14] 0 0
Up to 3 years

Eligibility
Key inclusion criteria
- Applicable to all Patients

- Patient is able to undergo apheresis of peripheral blood mononuclear cells (PBMC)
within eight weeks following registration.

- White cell count (WCC) <30/nL as higher WCC could interfere with the apheresis of
PBMC.

- Patient has an ECOG performance status of 0 - 1.

- Patient is deemed capable of undergoing the planned study procedures

- Patient has adequate organ function:

- bilirubin <1.5x upper limit of normal (ULN), AST/ALT =2.5 x ULN except in
patients with Gilbert's syndrome

- Serum Creatinine < 1.5 ×ULN or creatinine clearance > 50ml/min

- Amylase, lipase =1.5xULN

- Lymphocyte count of =0.5x109/L

- > 18 years of age.

- Patient has provided written informed consent.

- No chemotherapy or treatment with G-CSF within 4 weeks prior to the planned apheresis.

- Applicable to patients with multiple myeloma

- Patient has histologically or cytologically confirmed diagnosis of multiple myeloma
plus one or more of the criteria set out below must apply:

- Presence of the following features that are known to be associated with an adverse
prognosis with conventional chemotherapy, high-dose chemotherapy and autologous stem
cell transplant (AUSCT):

Chromosomal abnormalities:

- 13q deletion

- 17p deletion as p53-deletion by IHC on the bm trephine

- Translocation (4:14)

- Translocation (14:16)

Clinical features:

- Progressive disease within 12 months after previous AUSCT

- Plasmablastic morphology

- Plasma cell leukaemia

- Patient planned for high-dose melphalan chemotherapy with AUSCT having had at
least two prior treatment regimens (which can include prior high-dose
chemotherapy and AUSCT and must include at least one of thalidomide, lenalidomide
or bortezomib).

- Patient has previously proven LewisY expression on the plasma cells prior to
study entry in an analysis as defined in study criteria

- Patient is planned to receive high dose melphalan and autograft (after apheresis
of PBMC)

- Additional inclusion Criteria applied to patients with acute myeloid leukaemia
(AML)/high-risk myelodysplastic syndrome (MDS)

All of the following must apply:

- Patient must either have newly diagnosed AML/high-risk MDS with a poor prognosis or
relapsed/refractory AML/high-risk MDS

- Patient has previously proven LewisY expression on the myeloblasts prior to study
entry in an analysis as defined in study criteria

- Patient is planned to receive fludarabine containing regime (FCR) chemotherapy (after
apheresis of PBMC) which is planned to be the last cycle of FCR chemotherapy, no
further FCR chemotherapy should be planned within 3 months after this cycle of FCR

Definition of poor prognosis in AML/high-risk MDS

A patient with AML has a poor prognosis if any of the following is satisfied:

- Age > 65 years

- Age 56 - 65 years with any of the following single cytogenetic abnormalities: -7, -5,
trisomy 8, abnormal 3q, t(6;9), t(9;22) or t(9;11), normal karyotype with FLT3-ITD

- Age 56 - 65 years with a complex aberrant karyotype defined as >4 cytogenetic
abnormalities

- Any age with relapsed or refractory disease
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

None of the following should apply:

- Patient has had immunotherapy including corticosteroids (except Prednisolone <10mg or
equivalent) within the last 4 weeks or is planned to receive such therapy prior to
apheresis of PBMC.

- Patient has been given chemotherapy and/or G-CSF in the last 4 weeks.

- Patient has been planned to receive chemotherapy and/or growth factors of any type
before planned apheresis of PBMC

- Patient has been given experimental therapy within the last 4 weeks or is planned to
receive experimental therapy prior to apheresis of PBMC

- Patient has known clinically significant autoimmune disease with positive serology for
RHF (>20kU/L) or ANA (titre >1:40)

- Patient has a history of idiopathic pancreatitis Patient has known, biopsy proven
autoimmune inflammatory disease of the gastrointestinal tract

- Women of child bearing potential (WOCBP) who are unwilling or unable to use an
effective method of contraception to avoid pregnancy for the entire study period and
for at least 3 months after completion of study treatment.

- Women who are pregnant or breastfeeding.

- Men who are unwilling or unable to use an acceptable method of contraception for the
entire study period and for at least 3 months after completion of study treatment if
their sexual partners are WOCBP.

- Patient has known central nervous system (CNS) disease.

- Patient has a serious uncontrolled medical disorder which would impair the ability to
receive protocol therapy.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Unknown status
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/01/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2013
Actual
Sample size
Target
6
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
3002 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Peter MacCallum Cancer Centre, Australia
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Patients with some forms of acute myeloid leukemia (AML) and multiple myeloma (MM) are not
cured with conventional therapy and new approaches are needed. For the last 15 years we have
investigated the potential of using a patient's own T cells (a type of white blood cell
[WBC]) to eradicate the tumor. We have demonstrated the feasibility of this approach in cell
culture and animal models of AML and MM. Over the last 5 years we have been preparing to
treat patients as part of a Phase I (first in human) clinical trial.

The trial treatment involves collecting the patient's own WBCs from the blood by a standard
well established and safe process called apheresis. The cells are then cultured in a
specialized laboratory (under Good Manufacturing Practice conditions, similar to standards
under which pharmaceuticals are produced) over 12 days to convert the cells to specialized
tumor-attacking T cells. Early in that culture process the cells are exposed to a virus (that
is modified so that it cannot infect or replicate outside the special culture conditions)
that contains a special gene. Via the virus, this gene inserts into the patient's T cells in
culture and gets incorporated into the T cell's genetic machinery. As the T cells replicate,
the new gene produces a protein receptor that becomes part of the patient's T cells. This
protein receptor on the T cells has the capacity to specifically recognize and bind to a
protein on the leukemia or myeloma cells called the "Lewis Y" antigen.

After the modified T cells are infused into the patient, they home into the bone marrow (this
tracking is monitored by special radiological techniques) where the new protein receptor on
the T cell surface can recognize and bind to the cancer cells (which express Lewis Y). Once
bound onto the cancer cells, the T cells get activated and subsequently replicate and kill
the cancer cells. The novelty of this approach is that the T-cells will only kill cells that
have the Lewis Y on their surface - the cancer cells. Moreover, because there are few normal
cells in a person's body that carry Lewis Y, this treatment is likely to only have minor side
effects.

This gene therapy trial is unique and although the primary purpose is to test the safety of
this approach, patients will be monitored closely for anti-tumor responses. As the trial
progresses, the dose of T cells infused will increase, in the hope that this will result in a
better and stronger immune response to the leukemia or myeloma.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01716364
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Miles Prince, MD
Address 0 0
Peter MacCallum Cancer Centre, Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01716364