Study to Investigate the Safety and Clinical Activity of GSK3326595 and Other Agents to Treat Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML)

GlaxoSmithKline (GSK)

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Neoplasms

Treatments: Drug: GSK3326595; Drug: 5-Azacitidine

Study type: Interventional

Funder types: Industry

Identifiers

NCT03614728

208809

Details and patient eligibility

About

This study will evaluate the safety, tolerability, and clinical activity of GSK3326595 in participants with relapsed and refractory MDS, chronic myelomonocytic leukemia (CMML), and AML. The study will be conducted in 2 parts: Part 1 will determine the clinical benefit rate (CBR) of GSK3326595 in monotherapy and Part 2 will be expanded to study GSK3326595 in combination with 5-Azacitidine which will be composed of a dose escalation phase followed by dose expansion cohort of GSK3326595.

Enrollment: 30 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Males and females greater than or equal to (>=)18 years of age (at the time consent is obtained).
• Diagnosis of MDS, CMML or AML
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 or 2
• Adequate organ function
• A woman of childbearing potential (WOCBP) must have a negative highly sensitive serum pregnancy test within 7 days before the first dose of study intervention.

Exclusion criteria

• History of, or known, central nervous system (CNS) involvement
• Prior solid organ transplantation
• Known allergies, hypersensitivity, or intolerance to GSK3326595 or 5-Azacitidine or its excipient
• Prior therapy with any Protein arginine methyl transferase 5 (PRMT5) inhibitor
• History of a second malignancy, excluding non-melanoma skin cell cancer, within the last three years
• Active severe or uncontrolled infection
• History of optic nerve neuropathy or neuritis.
• History of sensitivity to any of the study medications, or components thereof, or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

30 participants in 3 patient groups

Part 1: Participants receiving GSK3326595

Experimental group

Treatment:

Drug: GSK3326595

Part 2 Dose escalation : Participants receiving GSK3326595+5-Azacitidine

Experimental group

Treatment:

Drug: 5-Azacitidine

Drug: GSK3326595

Part 2 Dose expansion: Participants receiving GSK3326595+5-Azacitidine

Experimental group

Treatment:

Drug: 5-Azacitidine

Drug: GSK3326595