Study of Clinical Efficacy and Safety of Tosedostat in MDS

NCT02452346 | Completed Phase 2 Results

• 1 other identifier: 1409015482
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Study WCMC IST-CTI-MDS evaluates the safety and tolerability of tosedostat in adult patients with pathologically confirmed MDS (\< 20% blasts in bone marrow, peripheral blood, or both) by World Health Organization (WHO) classification after failure of hypomethylating agent-based therapy.

Conditions

Myelodysplastic Syndrome

Keywords

MDS

Outcome Measures

Primary Outcomes (1)

• Over All Survival

  Survival following treatment to the date of death, assessed up to a period of 3-4 years.

  from start of treatment until death, assessed up to a period of 3-4 years.

Secondary Outcomes (2)

• Overall Response

  Approximately 3 years

• One Year and Two Year Survival

  from start of treatment to 1 year and 2 years post treatment initiation

Study Arms (1)

All Patients

EXPERIMENTAL

Tosedostat 120 mg PO once daily will be administered.

Drug: Tosedostat

Interventions

Tosedostat DRUG

120 mg PO once daily continuously for each 28 day treatment cycle

Also known as: CHR-2797

All Patients

Eligibility Criteria

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

You may qualify if:

• Able to understand and to provide written informed consent
• At least 18 years of age with pathologically confirmed MDS (\<20% blasts in bone marrow, peripheral blood, or both) within 6 weeks prior to screening by WHO classification
• Must have received at least 4 cycles of decitabine-based or 6 cycles of azacitidine-based therapy and are either refractory to, relapsed after or intolerant to prior therapy with either agent.
• Primary failure/refractory: Stable or worsening disease after a minimum of 4 cycles of decitabine-based or 6 cycles of azacitidine-based therapy
• Secondary failure/relapse: Bone marrow blast count increase or loss of hematologic response after initial treatment response with hypomethylating agent-based therapy
• Intolerance: Intolerance of hypomethylating agent-based therapy regardless of number of cycles completed and clinical response
• Progression (according to 2006 IWG criteria) at any time after initiation of subcutaneous or intravenous azacitidine or decitabine treatment per labeling during the past 2 years, defined as follows:
• For patients with \<5% BMBL, ≥ 50% increase in BMBL to \>5% BMBL
• For patients with 5-10% BMBL, ≥ 50% increase in BMBL to \>10% BMBL
• For patients with 10-20% BMBL, ≥ 50% increase in BMBL to \>20% BMBL
• For patients with 20-30% BMBL, ≥ 50% increase in BMBL to \>30% BMBL
• Any of the following:
• ≥ 50% decrease from maximum remission/response levels in granulocytes or PLT
• Decrease in Hgb concentration by ≥2 g/dL
• Transfusion dependence, defined as administration of at least 4 RBC units in the past 8 weeks before Screening (patients must have Hgb values \< 9 g/dL prior to transfusion to be considered), in the absence of another explanation.

You may not qualify if:

• Presence of AML (≥20% blasts in bone marrow, peripheral blood, or both)
• Presence of serious illness, medical condition, or other medical history, involving the heart, kidney, liver, or other organ system, including abnormal laboratory parameters, which, in the opinion of the Investigator, would be likely to interfere with a subject's participation in the study or with the interpretation of the results.
• Have known active central nervous system disease or active, uncontrolled, clinically significant infection(s)
• Have other active malignancies (including other hematologic malignancies) or other malignancies within 12 months before enrollment, except non-melanoma skin cancer or cervical intraepithelial neoplasia
• Are receiving any other investigational therapy or protocol-prohibited therapy
• Have received previous treatment with tosedostat
• Pregnant or breastfeeding females
• Any prior or co-existing medical condition that in the Investigator's judgment will substantially increase the risk associated with the subject's participation in the study
• Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary study procedures
• Significant\* cardiovascular disease defined as:
• Active heart disease including myocardial infarction within 6 months prior to study entry
• Symptomatic coronary artery disease
• Uncontrolled or clinically significant arrhythmia, angina, congestive heart failure
• Presence of clinically significant valvular heart disease
• Presence of clinically significant conduction defect on screening ECG

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• CTI BioPharma: collaborator

Study Sites (1)

Weill Cornell Medical College

New York, New York, 10065, United States

Location

Related Publications (1)

• Lee S, Desai P, Edirisinghe B, Pianello S, Curcio T, Samuel M, Ritchie EK, Roboz GJ. Phase II study of the clinical efficacy and safety of tosedostat in patients with myelodysplastic syndromes (MDS) after failure of hypomethylating agent-based therapy. Leuk Lymphoma. 2021 Feb;62(2):498-500. doi: 10.1080/10428194.2020.1832674. Epub 2020 Oct 10. No abstract available.

  PMID: 33043735 DERIVED

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

tosedostat

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Dr. Sangmin Lee, MD
• Organization: Weill Cornell Medicine

sal9053@med.cornell.edu

646-962-2700

Study Officials

• Gail Roboz, 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: January 28, 2015
• First Posted: May 22, 2015
• Study Start: March 20, 2015
• Primary Completion: October 25, 2017
• Study Completion: October 25, 2017
• Last Updated: June 12, 2018
• Results First Posted: June 12, 2018

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)