Acute Myeloid Leukemia Clinical Trial

A Study of Siremadlin in Combination With Venetoclax Plus Azacitidine in Adult Participants With Acute Myeloid Leukemia (AML) Who Are Ineligible for Chemotherapy.

Summary

A study of siremadlin in combination with venetoclax plus azacitidine in adult participants with AML who are ineligible for chemotherapy.

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Full Description

The primary purpose of this study is to assess whether siremadlin in combination with venetoclax plus azacitidine can enhance the clinical response in unfit AML patients without unacceptable levels of treatment-emergent toxicities. The recommended dose of siremadlin in combination with venetoclax plus azacitidine will be determined to be explored further in the expansion phase and the preliminary efficacy in achieving Complete Remission (CR) will be evaluated in participants who responded sub-optimally to first-line venetoclax plus azacitidine treatment.

The study will be conducted in two parts. The primary purpose of Part 1 (Safety Run-in) is to rule out excessive toxicity of siremadlin when administered in combination with venetoclax plus azacitidine while the primary purpose of Part 2 (Expansion) is to evaluate the preliminary efficacy of siremadlin when combined with venetoclax plus azacitidine in the respective patient population.

The study treatment (siremadlin in combination with venetoclax plus azacitidine) will be administered in cycles with a planned duration of 28 days and will continue until the participants experience disease progression/relapse or unacceptable toxicity.

In the Safety run-in part, 9-15 participants will be enrolled in each arms. Approximately 3-6 participants will be enrolled at the starting dose level of siremadlin in combination with venetoclax plus azacitidine in both arms independently. Provided the starting dose level is determined to be safe, approximately 6-9 additional participants will be enrolled at dose level +1. Safety review meetings will take place involving participating investigators and the Sponsor Team to make decisions regarding siremadlin dose and determine the recommended dose for expansion. Approximately 26 patients will be treated at the recommended dose in the expansion part.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

- Age at the date of signing the informed consent form (ICF): Arm 1 and Arm 2: ≥ 18 years

- Participants diagnosed with AML based on WHO 2016 classification (Arber et al 2016) who are ineligible for standard induction chemotherapy and: Arm 1 : have received at least 2 cycles and not more than 4 cycles of first-line venetoclax plus azacitidine treatment and have not achieved a CR, CRi, CRh or MLFS.

Arm 2 : newly diagnosed AML with adverse genetic risk stratification (according to ELN 2017) (except TP53 mutation positive participants).

Participant must be considered ineligible for standard of care intensive induction chemotherapy defined by the following:

75 years of age; OR
18 to 74 years of age with at least one of the following co-morbidities: Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 or 3; Cardiac history of congestive heart failure (CHF) requiring treatment or Ejection Fraction ≤ 50% or chronic stable angina; DLCO ≤ 65% or FEV1 ≤ 65%.

Participants must have an ECOG performance status:

0 to 2 for participants ≥ 75 years of age. OR 0 to 3 for participants ≥ 18 to 74 years of age.

WBC < 25x109/L
AST and ALT ≤ 3 × ULN
Estimated Glomerular Filtration Rate (eGFR)≥ 60 mL/min/1.73 m2

Exclusion Criteria:

Prior exposure to MDM2-inhibitor therapy at any time.
Participants with TP53 mutation positive, as defined by local TP53 testing.
Participants with del17p.
Participants with AML-M3 / APL (Acute promyelocytic leukemia) with PML-RARA (Promyelocytic leukemia/retinoic acid receptor alpha) or with AML secondary to Down's syndrome.
Participants treated with FLT3 inhibitors
Participants who require treatment with moderate or strong CYP3A4 inducers within 14 days prior to starting study treatment, or are expected to receive moderate or strong CYP3A4 inducers during the entire study
Participants who require treatment with substrates of CYP3A4/5 with a narrow therapeutic index.

Other protocol-defined inclusion/exclusion criteria may apply at the end

Study is for people with:

Acute Myeloid Leukemia

Phase:

Phase 1

Estimated Enrollment:

55

Study ID:

NCT05155709

Recruitment Status:

Recruiting

Sponsor:

Novartis Pharmaceuticals

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There are 19 Locations for this study

See Locations Near You

UCLA Medical Center
Los Angeles California, 90095, United States More Info
Contact
310-825-9111
Caspian Oliai
Principal Investigator
Rocky Mountain Cancer Centers RMCC - Aurora
Longmont Colorado, 80501, United States More Info
Bobbie Donnachaidh
Contact
303-418-7600
[email protected]
Christopher Benton
Principal Investigator
Oregon Health and Science University
Portland Oregon, 97239, United States More Info
Nicole Tong
Contact
503-346-7894
[email protected]
Elie Traer
Principal Investigator
Texas Oncology Sammons Cancer Center Sammons Cancer Center (SC)
Dallas Texas, 78246, United States More Info
Valdez Ericka R
Contact
[email protected]
Moshe Levy
Principal Investigator
University of Texas MD Anderson Cancer Center
Houston Texas, 77030, United States More Info
Contact
713-794-5783
Naval Daver
Principal Investigator
Virginia Cancer Specialists
Fairfax Virginia, 22031, United States More Info
Karina Castillo Grady
Contact
703-280-5390
[email protected]
Mitul Gandhi
Principal Investigator
Novartis Investigative Site
Perth Western Australia, 6000, Australia
Novartis Investigative Site
Hong Kong , , Hong Kong
Novartis Investigative Site
Budapest , 1085, Hungary
Novartis Investigative Site
Beer-Sheva , 84571, Israel
Novartis Investigative Site
Jerusalem , 91031, Israel
Novartis Investigative Site
Jerusalem , 91120, Israel
Novartis Investigative Site
Bologna BO, 40138, Italy
Novartis Investigative Site
Milano MI, 20162, Italy
Novartis Investigative Site
Alor Setar Kedah, 05460, Malaysia
Novartis Investigative Site
Kuala Lumpur , 59100, Malaysia
Novartis Investigative Site
Selangor , 68000, Malaysia
Novartis Investigative Site
Bern , 3010, Switzerland
Novartis Investigative Site
Ankara Yenimahalle, 06200, Turkey
Novartis Investigative Site
Izmir , 35340, Turkey

How clear is this clinincal trial information?

Study is for people with:

Acute Myeloid Leukemia

Phase:

Phase 1

Estimated Enrollment:

55

Study ID:

NCT05155709

Recruitment Status:

Recruiting

Sponsor:


Novartis Pharmaceuticals

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