A Phase II Study of SGI-110 in Philadelphia-Negative Myeloproliferative Neoplasms

NCT03075826 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 1510016613
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

• This is an open label single-arm, single-institution stud to evaluate the efficacy and safety of SGI-110 in Philadelphia chromosome negative (Ph-) Myeloproliferative Neoplasms (MPN) (excluding PV, ET and primary/secondary myelofibrosis). The study will enroll approximately 50 patients at the Weill Cornell Medical College.
• Enrollment onto this clinical study is expected to be completed in approximately 36 months. The total study duration will depend on individual response, evidence of disease progression and tolerance. Participants will be followed monthly for six months after removal from study or until death, whichever occurs first. Key eligibility:
• Confirmed diagnosis of Ph- MPN and had
• No chemotherapy or radiation treatment within 2 weeks prior to study entry.
• Subjects meet other protocol-defined criteria related to baseline screening procedures.

Conditions

Myeloproliferative Neoplasms

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Hematological Response, as Measured by Any One or More of the Following Response Assessments: IWG-MDS and IWG-MF Criteria as Accurate and Appropriate.

  The response to treatment will be measured from baseline through 12 cycles. A response assessment will be performed after cycle 3, cycle 6 and cycle 12. The response will be measured by IWG-MDS (International working group - Myelodysplastic Syndrome), which is a set of criteria that dictates what response a patient with MDS has had to a treatment; IWG-MF (International Working Group - Myelofibrosis) which is a set of criteria that dictates what response a patient with MF has had to a treatment. Both sets of criteria utilize the following parameters to asses response: Results from blood tests; bone marrow biopsies; physical exams to look at spleen and liver size; and symptoms. All responses will be recorded in our database and the best response to treatment will be reported. A cycle is at least 28 days, which can be extended past day 28 in order to allow physicians decision to delay next cycle based on the patients clinical needs.

  At the end of cycles 3, 6 and 12 - up to approximately 336 days

Secondary Outcomes (1)

• Number of Participants With Change in Quality of Life (QoL) Scores as Defined by Myeloproliferative Neoplasms Symptoms Assessment Form (MPN-SAF).

  Baseline, at the beginning of each new cycle - approximately every 28 days for up to 700 days

Study Arms (1)

Open Label-Single Arm

OTHER

This is a single arm, open-label study of SGI-110 in patients with MPN. SGI-110 will be administered subcutaneously at a dose of 60 mg/m2 on days 1-5, repeated every 28 days. Toxicity will be evaluated using the NCI Common Terminology Criteria for Adverse Events Active Version 4. The frequency of toxicities per organ system will be tabulated using descriptive statistics. All patients who receive any amount of the study drug will be evaluable for toxicity

Drug: SGI-110

Interventions

SGI-110 DRUG

subcutaneously at a dose of 60 mg/m2

Also known as: Guadecitabine

Open Label-Single Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have confirmed diagnosis of Philadelphia chromosome negative MPN neoplasm based on WHO classification (reference) including Chronic Neutrophilic Leukemia (CNL), atypical Chronic Myeloid Leukemia (aCML), Chronic Myelomonocytic Leukemia (CMML), MPN/MDS overlap syndromes, accelerated phase myelofibrosis and MPN unclassifiable.
• Age minimum of 18 years. Because no dosing or adverse event data are currently available on the use of SGI-110 in participants \<18 years of age, children are excluded from this study but may be eligible for future pediatric trials.
• ECOG performance status \<3
• Participants must have normal organ function as defined below:
• Total bilirubin \< or = 1.5 X institutional upper limit of normal unless attributable to underlying disease, hemolysis or documented Gilbert's syndrome
• AST (SGOT)/ALT (SGPT) \< 2.5 X institutional upper limit of normal unless attributable to underlying disease
• Creatinine \< 1.5add \< or = 1.5X institutional upper limit of normal or creatinine clearance add using Cockcroft Gault \> 50 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal.
• LVEF \< 40 % is allowed as long as there is no NY class III/IV heart failure or uncontrolled arrhythmias.
• The effects of SGI-110 on the developing human fetus are unknown. For this reason and because oncological agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Participants who have had any chemotherapy (investigational or FDA approved) (hydroxyurea is permitted) or radiotherapy within 2 weeks prior to study entry or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier.
• Participants may not be treated with any other investigational agents while on this study unless approved by the principal investigator AND the sponsors of BOTH investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to decitabine or SGI-110.
• Uncontrolled intercurrent illness including, but not limited to, infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because SGI-110 is a hypomethylating agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with SGI-110, breastfeeding should be discontinued.
• Individuals with a history of a different malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 3 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 3 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin.

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Astex Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Weill Cornell Medical College

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Myeloproliferative Disorders

Interventions

guadecitabine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Limitations and Caveats

The statistical analysis plan (and associated statistical power) was based on an expected sample size of 47 evaluable patients. Forty-six patients were consented and ultimately only 16 patients were evaluable. This reduced sample size was not sufficient for the statistical analysis plan as written, and, therefore, only descriptive statistics for the response proportions can be presented for the study.

Results Point of Contact

• Title: Dr.Pinkal Desai
• Organization: Weill Cornell Medical College

pid4006@med.cornell.edu

646-962-2700

Study Officials

• Pinkal Desai, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2017
• First Posted: March 9, 2017
• Study Start: March 15, 2016
• Primary Completion: March 31, 2021
• Study Completion: March 31, 2021
• Last Updated: May 5, 2022
• Results First Posted: April 6, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)