NCT02907359

Guadecitabine (SGI-110) vs Treatment Choice in Adults With MDS or CMML Previously Treated With HMAs

A Phase 3, Multicenter, Randomized, Open-Label Study of Guadecitabine (SGI-110) Versus Treatment Choice in Adults With Myelodysplastic Syndromes (MDS) or Chronic Myelomonocytic Leukemia (CMML) Previously Treated With Hypomethylating Agents

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 417 (actual)
• Sponsor: Astex Pharmaceuticals, Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

A Phase 3, randomized, open-label, parallel-group, multicenter study designed to evaluate the efficacy and safety of guadecitabine in participants with MDS or CMML who failed or relapsed after adequate prior treatment with azacitidine, decitabine, or both. This global study will be conducted in approximately 15 countries. Approximately 408 participants from approximately 100 study centers will be randomly assigned in a 2:1 ratio to either guadecitabine (approximately 272 participants) or Treatment Choice (approximately 136 participants). The study consists of a 21-day screening period, a treatment period, a safety follow-up visit, and a long-term follow-up period. The study is expected to last more than 2 years, and the duration of individual participant participation will vary. Participants may continue to receive treatment for as long as they continue to benefit.

Detailed description

Multicenter, randomized, open-label, parallel-group study of guadecitabine vs Treatment Choice (TC). Approximately 408 participants will be randomly assigned 2:1 to either guadecitabine or TC. * Guadecitabine: approximately 272 participants. * TC: approximately 136 participants. Before randomization, the investigator will assign each participant to one of the following TC options: * Low dose cytarabine (LDAC). * Standard Intensive Chemotherapy (IC) of a 7+3 regimen. * Best Supportive Care (BSC) only. BSC will be provided to all participants as per standard and institutional practice. Participants randomized to TC will not be allowed to cross over to guadecitabine. Data will be reviewed by an independent Data Monitoring Committee at regular intervals, primarily to evaluate safety during study conduct. Randomization will be stratified by disease category (MDS vs CMML), bone marrow (BM) blasts (BM blasts \>10% vs BM blasts ≤10%), TC option (LDAC vs IC vs BSC), and study center region. Guadecitabine: 60 milligrams per square meter (mg/m\^2) given subcutaneously (SC) daily on Days 1-5 in 28-day cycles (delayed as needed to allow blood count recovery). Treatment should be given for at least 6 total cycles in the absence of unacceptable toxicity or disease progression requiring alternative therapy. Beyond 6 cycles, treatment should continue as long as the participant continues to benefit. BSC should be given according to standard and institutional practice. Treatment Choice (TC): Before randomization, the investigator will assign each participant to one of the following TC options: * Low dose cytarabine (LDAC) given as 20 mg/m\^2 SC or intravenously (IV) once daily for 14 days in 28-day cycles (delayed as needed to allow blood count recovery). Treatment should be given for at least 4 cycles in the absence of disease progression or unacceptable toxicity. * Standard Intensive Chemotherapy (IC) of a 7+3 regimen: given as cytarabine 100-200 mg/m\^2/day given as continuous infusion for 7 days and an anthracycline given as per institutional standard practice such as daunorubicin (45-60 mg/m\^2/day), or idarubicin (9-12 mg/m\^2/day), or mitoxantrone (8-12 mg/m\^2/day) by intravenous infusion for 3 days. * Best Supportive Care (BSC) only: given according to standard and institutional practice. BSC includes, but is not limited to blood transfusions (Red blood cells \[RBCs\] or platelets), growth factors including erythropoiesis stimulating agents (ESA), granulocyte stimulating factors (GSFs), iron chelating therapy, and broad-spectrum antibiotics and/or antifungals.

Conditions

• Myelodysplastic Syndromes
• Leukemia, Myelomonocytic, Chronic

Interventions

Type	Name	Description
DRUG	Guadecitabine
OTHER	Treatment Choice	* BSC: according to standard/institutional practice; included RBC or platelet transfusions; growth factors, i.e. erythropoiesis stimulating agents, granulocyte stimulating factors, iron chelating therapy; broad spectrum antibiotics and/or antifungals. * LDAC: 20 mg/m\^2 SC or IV once daily (QD) for 14 days in 28-day cycles. Other schedules were allowed per institutional practice. Treatment for ≥4 cycles absent disease progression/toxicity. BSC per institutional/standard practice. * Standard Intensive Chemotherapy: recommended regimen of 7+3 was given as cytarabine 100-200 mg/m\^2/day continuous infusion for 7 days and an anthracycline for 3 days. Anthracyclines per institutional practice included daunorubicin (45-60 mg/m\^2/day) or idarubicin (9-12 mg/m\^2/day) or mitoxantrone (8-12 mg/m\^2/day) by IV infusion. Participants with complete or partial response after IC induction received ≥1 additional cycles with reduced cytotoxic doses then BSC per standard /institutional practice.

Timeline

• Start date: 2017-01-13
• Primary completion: 2020-03-31
• Completion: 2020-11-30
• First posted: 2016-09-20
• Last updated: 2024-08-27
• Results posted: 2023-05-18

Locations

112 sites across 14 countries: United States, Belgium, Canada, Czechia, Denmark, France, Germany, Italy, Japan, Poland, South Korea, Spain, Sweden, United Kingdom

Regulatory

• FDA-regulated drug study