Description:
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.
Title
- Brief Title: Study of PDR001 and/or MBG453 in Combination With Decitabine in Patients With AML or High Risk MDS
- Official 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
Clinical Trial IDs
- ORG STUDY ID:
CPDR001X2105
- NCT ID:
NCT03066648
Conditions
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Myelodysplastic Syndromes
- Preleukemia
- Bone Marrow Diseases
- Hematologic Diseases
Interventions
Drug | Synonyms | Arms |
---|
Decitabine | 5-aza-2'-deoxycytidine | Decitabine and MBG453 |
PDR001 | | Decitabine and PDR001 |
MBG453 | | Decitabine and MBG453 |
Purpose
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 Arms
Name | Type | Description | Interventions |
---|
Decitabine and PDR001 | Experimental | Decitabine in combination with PDR001 | |
Decitabine and MBG453 | Experimental | Decitabine in combination with MBG453 | |
Decitabine, PDR001 and MBG453 | Experimental | Decitabine in combination with PDR001 and MBG453 | |
MBG453 | Experimental | MBG453 alone | |
MBG453 and PDR001 | Experimental | MBG453 in combination with PDR001 | |
Eligibility 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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Safety of MBG453 single agent treatment or MBG453 in combination with PDR001 or PDR001 and/or MBG453 in combination with decitabine. |
Time Frame: | 24 months |
Safety Issue: | |
Description: | Incidence and severity of AEs and SAEs |
Secondary Outcome Measures
Measure: | AUC of PDR001, MBG453 and decitabine. |
Time Frame: | 24 months |
Safety Issue: | |
Description: | AUC |
Measure: | Cmax of PDR001, MBG453 and decitabine |
Time Frame: | 24 months |
Safety Issue: | |
Description: | Cmax |
Measure: | Tmax of PDR001, MBG453 and decitabine |
Time Frame: | 24 months |
Safety Issue: | |
Description: | Tmax |
Measure: | Half-life of PDR001, MBG453 and decitabine |
Time Frame: | 24 months |
Safety Issue: | |
Description: | Half-life |
Measure: | Concentration vs time profile of PDR001, MBG453 and decitabine |
Time Frame: | 24 months |
Safety Issue: | |
Description: | Concentration vs. time |
Measure: | Overall Response Rate (ORR) |
Time Frame: | 24 months |
Safety Issue: | |
Description: | Determine ORR in each arm of the study |
Measure: | Best Overall Response (BOR) |
Time Frame: | 24 months |
Safety Issue: | |
Description: | Determine BOR in each arm of the study |
Measure: | Progression Free Survival (PFS) |
Time Frame: | 24 months |
Safety Issue: | |
Description: | Determine PFS in each arm of the study |
Measure: | Time to Progression (TTP) |
Time Frame: | 24 months |
Safety Issue: | |
Description: | Determine TTP in each arm of the study |
Measure: | Duration of Response (DOR) |
Time Frame: | 24 months |
Safety Issue: | |
Description: | Determine DOR in each arm of the study |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Novartis Pharmaceuticals |
Trial Keywords
- Acute Myeloid Leukemia
- Myelodysplastic syndromes
Last Updated
May 12, 2020