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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03066648
Ethics application status
Date submitted
18/02/2017
Date registered
28/02/2017

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
2016-005060-33
Secondary ID [2] 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
Chronic Myelomonocytic Leukemia 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
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
Treatment: Drugs - Decitabine
Treatment: Drugs - PDR001
Treatment: Drugs - MBG453
Treatment: Drugs - Azacitidine

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

Experimental: Azacitidine and MBG453 - Azacitidine in combination with MBG453


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).

Treatment: Drugs: Azacitidine
Azacitidine (5-azacytidine) is a cytidine nucleoside analogue that selectively inhibits DNA methyltransferases at low doses, resulting in gene promoter hypomethylation
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 or azacitidine.
Timepoint [1] 0 0
24 months
Primary outcome [2] 0 0
Incidence of Dose Limiting Toxicities (DLTs)
Timepoint [2] 0 0
2 months
Primary outcome [3] 0 0
Incidence of Dose Limiting Toxicities (DLTs)
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 or azacitidine.
Timepoint [4] 0 0
24 months
Secondary outcome [1] 0 0
AUC of PDR001, MBG453, decitabine and azacitidine.
Timepoint [1] 0 0
24 months
Secondary outcome [2] 0 0
Cmax of PDR001, MBG453, decitabine and azacitidine
Timepoint [2] 0 0
24 months
Secondary outcome [3] 0 0
Tmax of PDR001, MBG453, decitabine and azacitidine
Timepoint [3] 0 0
24 months
Secondary outcome [4] 0 0
Half-life of PDR001, MBG453, decitabine and azacitidine
Timepoint [4] 0 0
24 months
Secondary outcome [5] 0 0
Overall Response Rate (ORR)
Timepoint [5] 0 0
24 months
Secondary outcome [6] 0 0
Best Overall Response (BOR)
Timepoint [6] 0 0
24 months
Secondary outcome [7] 0 0
Progression Free Survival (PFS)
Timepoint [7] 0 0
24 months
Secondary outcome [8] 0 0
Time to Progression (TTP)
Timepoint [8] 0 0
24 months
Secondary outcome [9] 0 0
Duration of Response (DOR)
Timepoint [9] 0 0
24 months
Secondary outcome [10] 0 0
Number of participants with anti-PDR001 and anti-MBG453 antibodies
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:
* Relapsed/refractory AML following =1 prior therapies who have relapsed or exhibited refractory disease (primary failure) 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)
* Newly diagnosed 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)
* Intermediate or high risk MDS or MDS/MPN including CMML (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)
* Intermediate or high risk MDS or MDS/MPN including CMML 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.)

Arm 6:
* Newly diagnosed AML patients who are suitable for treatment with azacitidine (patients who are suitable for standard induction chemotherapy or hematopoietic stem cell transplantation and willing to receive it are excluded) (Arm 6a)
* Intermediate or high-risk MDS or MDS/MPN including CMML (patients who are suitable for standard induction chemotherapy or hematopoietic stem cell transplantation and willing to receive it are excluded) (Arm 6b)
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.
6. Arm 6: Patients must be fit for standard treatment with azacitidine as determined by the investigator and as per the local azacitidine package insert.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Arms 1-3 or Arm 6: Patients who have received prior hypomethylating agent treatment for AML or MDS.
2. Patients with active, known or suspected autoimmune disease. Patients with vitiligo, type I diabetes, residual hypothyroidism only requiring hormone replacement, psoriasis not requiring systemic treatment or conditions not expected to recur should not be excluded.
3. History of, or current drug-induced interstitial lung disease or pneumonitis grade = 2.
4. Patients who discontinued prior PD-1 or PD-L1 directed therapy due to a treatment related toxicity should not be included in the PDR001 containing arms of the study. Patients previously exposed to anti-PD-1/PD-L1 treatment who are adequately treated for skin rash or with replacement therapy for endocrinopathies should not be excluded.
5. Systemic antineoplastic therapy (including cytotoxic chemotherapy, alphainterferon, kinase inhibitors or other targeted small molecules, and toxinimmunoconjugates) or any experimental therapy within 14 days or 5 half-lives, whichever is shorter, before the first dose of study treatment.
6. Systemic chronic corticosteroid therapy (>10 mg/day prednisone or equivalent) or any immunosuppressive therapy within 7 days of first dose of study treatment. Topical, inhaled, nasal and ophthalmic steroids are allowed.

Other protocol-defined inclusion/exclusion criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
6/07/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
8/09/2023
Sample size
Target
Accrual to date
Final
241
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
Trial website
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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT03066648