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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03066648




Registration number
NCT03066648
Ethics application status
Date submitted
18/02/2017
Date registered
28/02/2017
Date last updated
17/07/2019

Titles & IDs
Public title
Study of PDR001 and/or MBG453 in Combination With Decitabine in Patients With AML or High Risk MDS
Scientific title
Phase 1b, Multi-arm, Open-label Study of PDR001 and/or MBG453 in Combination With Decitabine in Patients With Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome
Secondary ID [1] 0 0
CPDR001X2105
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Leukemia 0 0
Leukemia, Myeloid 0 0
Leukemia, Myeloid, Acute 0 0
Myelodysplastic Syndromes 0 0
Preleukemia 0 0
Bone Marrow Diseases 0 0
Hematologic Diseases 0 0
Condition category
Condition code
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above
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
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Decitabine
Treatment: Drugs - PDR001
Treatment: Drugs - MBG453

Experimental: Decitabine and PDR001 - Decitabine in combination with PDR001

Experimental: Decitabine and MBG453 - Decitabine in combination with MBG453

Experimental: Decitabine, PDR001 and MBG453 - Decitabine in combination with PDR001 and MBG453

Experimental: MBG453 - MBG453 alone

Experimental: MBG453 and PDR001 - MBG453 in combination with PDR001


Treatment: Drugs: Decitabine
Decitabine is a cytidine deoxynucleoside analogue that selectively inhibits DNA methyltransferases at low doses, resulting in gene promoter hypomethylation.

Treatment: Drugs: PDR001
PDR001 is a high-affinity, ligand-blocking, humanized IgG4 monoclonal antibody directed against PD-1 that blocks the binding of PD-L1 and PD-L2.

Treatment: Drugs: MBG453
MBG453 is a high-affinity, humanized anti-TIM-3 IgG4 monoclonal antibody which blocks the binding of TIM-3 to phosphatidylserine (PtdSer).

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety of MBG453 single agent treatment or MBG453 in combination with PDR001 or PDR001 and/or MBG453 in combination with decitabine. - Incidence and severity of AEs and SAEs
Timepoint [1] 0 0
24 months
Primary outcome [2] 0 0
Incidence of Dose Limiting Toxicities (DLTs) - The incidence of DLTs during the first two cycles of treatment with MBG453 in combination with PDR001 or PDR001 and/or MBG453 in combination with decitabine.
Timepoint [2] 0 0
2 months
Primary outcome [3] 0 0
Incidence of Dose Limiting Toxicities (DLTs) - The incidence of DLTs during the first cycle of treatment with MBG453.
Timepoint [3] 0 0
1 month
Primary outcome [4] 0 0
Tolerability of MBG453 single agent treatment or MBG453 in combination with PDR001 or PDR001 and/or MBG453 in combination with decitabine. - Incidence and severity of AEs and SAEs
Timepoint [4] 0 0
24 months
Secondary outcome [1] 0 0
AUC of PDR001, MBG453 and decitabine. - AUC
Timepoint [1] 0 0
24 months
Secondary outcome [2] 0 0
Cmax of PDR001, MBG453 and decitabine - Cmax
Timepoint [2] 0 0
24 months
Secondary outcome [3] 0 0
Tmax of PDR001, MBG453 and decitabine - Tmax
Timepoint [3] 0 0
24 months
Secondary outcome [4] 0 0
Half-life of PDR001, MBG453 and decitabine - Half-life
Timepoint [4] 0 0
24 months
Secondary outcome [5] 0 0
Concentration vs time profile of PDR001, MBG453 and decitabine - Concentration vs. time
Timepoint [5] 0 0
24 months
Secondary outcome [6] 0 0
Overall Response Rate (ORR) - Determine ORR in each arm of the study
Timepoint [6] 0 0
24 months
Secondary outcome [7] 0 0
Best Overall Response (BOR) - Determine BOR in each arm of the study
Timepoint [7] 0 0
24 months
Secondary outcome [8] 0 0
Progression Free Survival (PFS) - Determine PFS in each arm of the study
Timepoint [8] 0 0
24 months
Secondary outcome [9] 0 0
Time to Progression (TTP) - Determine TTP in each arm of the study
Timepoint [9] 0 0
24 months
Secondary outcome [10] 0 0
Duration of Response (DOR) - Determine DOR in each arm of the study
Timepoint [10] 0 0
24 months

Eligibility
Key inclusion criteria
1. Written informed consent must be obtained prior to any screening procedures

2. Male or female patients = 18 years of age who present with one of the following:

Arms 1-3:

- Refractory/relapsed AML following =1 prior therapies and are deemed by the
investigator not to be candidates for standard therapy, including re-induction
with cytarabine or other established chemotherapy regimens for patients with AML
(patients who are suitable for standard re-induction chemotherapy or
hematopoietic stem cell transplantation and willing to receive it are excluded)

- De novo AML patients who are suitable for treatment with decitabine (patients who
are suitable for standard induction chemotherapy or hematopoietic stem cell
transplantation and willing to receive it are excluded)

- High risk MDS (patients who are suitable for standard re-induction chemotherapy
or hematopoietic stem cell transplantation and willing to receive it are
excluded)

Arms 4-5:

- Refractory / relapsed AML following =1 prior therapies (Arms 4a & 5a)

- High risk MDS who have failed hypomethylating agent therapy (Arms 4b & 5b) (Note:
hypomethylating agent failure is defined as progressive disease on
hypomethylating agent therapy or lack of clinically meaningful response as deemed
by investigator after at least 4 cycles of hypomethylating agent therapy.)

3. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status = 2

4. Patient must be a candidate for serial bone marrow aspirate and/or biopsy according to
the institutions guidelines and be willing to undergo a bone marrow aspirate
and/biopsy at screening, during and at the end of therapy on this study. Exceptions
may be considered after documented discussion with Novartis.

5. Arms 1-3: Patients must be fit for standard treatment with decitabine as determined by
the investigator and as per local decitabine package insert.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
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
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Melbourne
Recruitment postcode(s) [1] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Massachusetts
Country [2] 0 0
United States of America
State/province [2] 0 0
Oregon
Country [3] 0 0
United States of America
State/province [3] 0 0
Texas
Country [4] 0 0
Finland
State/province [4] 0 0
Helsinki
Country [5] 0 0
France
State/province [5] 0 0
Marseille
Country [6] 0 0
Germany
State/province [6] 0 0
Dresden
Country [7] 0 0
Germany
State/province [7] 0 0
Jena
Country [8] 0 0
Netherlands
State/province [8] 0 0
Amsterdam
Country [9] 0 0
Spain
State/province [9] 0 0
Catalunya
Country [10] 0 0
United Kingdom
State/province [10] 0 0
Cardiff

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
To characterize the safety and tolerability of 1) MBG453 as a single agent or in combination
with PDR001 or 2) PDR001 and/or MBG453 in combination with decitabine in AML and high risk
MDS patients, and to identify recommended doses for future studies.
Trial website
https://clinicaltrials.gov/show/NCT03066648
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Country 0 0
Phone 0 0
1-888-669-6682
Fax 0 0
Email 0 0
Novartis.email@novartis.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03066648