Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at San Francisco, California and other locations
Dates
study started
estimated completion
Principal Investigator
by Neil Dunavin
Headshot of Neil Dunavin
Neil Dunavin

Description

Summary

This trial will seek to extend the preliminary findings of efficacy of MBG453 in combination with hypomethylating agents (HMA) by evaluating MBG453 in combination with the HMA azacitidine and the Bcl-2 inhibitor venetoclax.

Official Title

A Phase II Multi-center, Single Arm, Safety and Efficacy Study of MBG453 in Combination With Azacitidine and Venetoclax for the Treatment of Acute Myeloid Leukemia (AML) in Adult Patients Unfit for Chemotherapy

Details

The purpose of the current study is to assess clinical effects of MBG453 in combination with hypomethylating agents (HMA) (azacitidine or decitabine) in adult subjects with International Prognostic Scoring System (IPSS-R) intermediate, high, very high risk MDS. The primary purpose of Part 1 (Safety Run-in) is to rule out excessive toxicity of MBG453, when administered in combination with azacitidine and venetoclax. The primary purpose of the combined Part 1 and Part 2 (Safety run-in and Expansion Part) is to evaluate efficacy of MBG453, when administered in combination with azacitidine and venetoclax in adult patients with newly diagnosed AML, who are not suitable for treatment with intensive chemotherapy. There will be one analysis of the CR rate, 7 months after the last randomized subject. PFS will not be tested at this time point. A maximum of two analyses will be performed for PFS. A PFS interim analysis will be scheduled when approximately 81 PFS events (after 75% of the planned target PFS events with an option to stop for efficacy) have been documented, expected to occur approximately 28 months after the first subject randomized. If PFS is not statistically significant at the IA, the study will continue until the final PFS analysis. The final PFS analysis will be performed after observing approximately 108 PFS events (or at the latest at 4 years after the last subject is randomized) expected to occur approximately 51 months after the first subject randomized.

Keywords

Acute Myeloid Leukemia MBG453 Venetoclax Azacitidine Phase 2 AML Sabatolimab Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute MBG453+Venetoclax +Azacitidine

Eligibility

You can join if…

Open to people ages 18 years and up

  1. Signed informed consent must be obtained prior to participation in the study.
  2. Age ≥ 18 years at the date of signing the informed consent form (ICF)
  3. Newly diagnosed with AML based on 2016 WHO classification (Arber et al 2016) and not suitable for intensive chemotherapy defined as: age ≥75, ECOG performance Status 2 or 3, or any of the following comomorbitities: severe cardiac comorbities (including congestive heart failure, LVEF ≤ 50%, chronic stable Angina) , pulmonary comorbidity (DLCO ≤ 65% or FEVI ≤ 65%). moderate hepatic impairment (with total Bilirubin >1.5 to 3x ULN) , renal impairment (eGFR≥ 30 ml/min/1.73m2 to 45 30 ml/min/1.73m2), or other comorbidity incompatible with intensive chemotherapy per Investigator assessement and approved by the Novartis Medical monitor)

  4. .Not planned for hematopoietic stem-cell transplantation (HSCT)
  5. .Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 , 2 or 3

You CAN'T join if...

  1. Prior exposure to TIM-3 directed therapy
  2. History of severe hypersensitivity reactions to any ingredient of study drug(s) (azacitidine, venetoclax or MGB453) or monoclonal antibodies (mAbs) and/or their excipients
  3. Current use or use within 14 days prior to randomization of systemic, steroid therapy (> 10 mg/day prednisone or equivalent) or any immunosuppressive therapy. Topical, inhaled, nasal, ophthalmic steroids are allowed. Replacement therapy, steroids given in the context of a transfusion are allowed and not considered a form of systemic treatment.
  4. Previous treatment at any time, with any of the following antineoplastic agents, approved or investigational; checkpoint inhibitors, venetoclax and hypomethylating agents (HMAs) such as decitabine or azacitidine.
  5. Active autoimmune disease requiring systemic therapy (e.g.corticosteroids).
  6. Live vaccine administered within 30 Days prior to randomization

Other protocol-defined Inclusion/Exclusion may apply.

Locations

  • UCSF Medical Center accepting new patients
    San Francisco California 94143 United States
  • Huntsman Cancer Institute Univ of Utah accepting new patients
    Salt Lake City Utah 84112 0550 United States

Lead Scientist at UCSF

  • Neil Dunavin
    Hematologist with interests in leukemia, stem cell transplantation, myelodysplastic syndrome, myeloproliferative neoplasms, aplastic anemia, bone marrow failure, rare diseases, and clinical trials.

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Novartis Pharmaceuticals
ID
NCT04150029
Phase
Phase 2 research study
Study Type
Interventional
Participants
Expecting 86 study participants
Last Updated