Extension Study Evaluating the Long Term Safety and Efficacy Study of CYT387 in Primary Myelofibrosis (PMF) or Post-polycythemia Vera (PV) or Post-essential Thrombocythemia (ET)

NCT01236638 | Completed Phase 2 DMC

• 1 other identifier: CCL09101E
• Study Type: interventional
• Target: 120
• Locations: 3 countries
• Sites: 6

Brief Summary

This extension protocol to the core study CCL09101 allows patients who have tolerated the drug and derived a clinical benefit, to continue to receive treatment beyond the 9 cycles of the core protocol. Long term safety and efficacy of CYT387 (momelotinib) will be evaluated.

Conditions

Primary Myelofibrosis; Post-Polycythemia Vera Myelofibrosis; Post-Essential Thrombocythemia Myelofibrosis

Keywords

Primary Myelofibrosis; Post-Polycythemia Vera; Post-Essential Thrombocythemia; CYT387 (momelotinib)

Outcome Measures

Primary Outcomes (2)

• To determine the long term safety and tolerability of orally-administered CYT387 in patients with PMF or post-ET/PV MF following completion of core study CCL09101

  Safety monitoring will be undertaken for all patients every 3 months

• To obtain information on the long term effectiveness of orally-administered CYT387 in patients with PMF or post-ET/PV MF

  Measured by complete response (CR) rate, partial response (PR) rate and clinical improvement (CI) rate according to IWG-MRT consensus criteria

  Every three months

Study Arms (1)

Momelotinib

EXPERIMENTAL

Drug: Momelotinib

Interventions

Momelotinib DRUG

Patients will continue receiving the same doses as assigned during the CCL09101 protocol; up to 400 mg once per day (QD). CYT387 will be administered orally as a single daily dose (at least 20 and no more than 28 hours apart, preferably in a fasted state at least two hours before and one hour after a meal), except for patients on the twice daily (BID) dosing regime (150 mg BID).

Also known as: CYT387

Momelotinib

Eligibility Criteria

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

You may qualify if:

• Patients must have completed at least 9 cycles of treatment on the core study 'A Phase I/II, Open-Label, Dose-Escalation Study Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Orally-Administered CYT387 in Primary Myelofibrosis or Post-Polycythemia Vera or Post-Essential Thrombocythemia Myelofibrosis (CCL09101)' and achieved stable disease (SD), clinical improvement (CI), partial remission (PR) or complete remission (CR) using the International Working Group consensus criteria for treatment responses in myelofibrosis with myeloid metaplasia (IWG-MRT; Tefferi et al., 2006)
• Must be able to provide informed consent and be willing to sign an informed consent form.
• Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
• Must have evidence of acceptable organ function within 7 days of initiating study drug as evidenced by the following:
• SGOT (AST) or SGPT (ALT) \<= 2.5 x upper limit of normal (ULN) (or \<= 5 x ULN if in the investigator's opinion the elevation is due to extramedullary hematopoiesis)
• Bilirubin \<= 2.0 x ULN or direct bilirubin \< 1.0
• Serum creatinine \<= 2.5 x ULN
• Absolute neutrophil count \>= 500/µL
• Platelet count \>= to 20,000/µL
• Females of childbearing potential must have a negative pregnancy test within 4 days of entering the extension protocol.

You may not qualify if:

• A delay of 4 weeks or more since the last preceding dose of CYT387 on the CCL09101 core study.
• Any chemotherapy (e.g., hydroxyurea), immunomodulatory drug therapy (e.g., thalidomide), immunosuppressive therapy, corticosteroids \> 10 mg/day prednisone or equivalent, or growth factor treatment (e.g., erythropoietin) within 14 days prior to initiation of study drug.
• Incomplete recovery from major surgery within four weeks of study entry.
• Radiation therapy within four weeks of study entry.
• Women of childbearing potential, unless surgically sterile for at least 3 months (i.e., hysterectomy), OR postmenopausal for at least 12 months (FSH \> 30 U/mL), OR unless they agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through end of study. Permitted methods for preventing pregnancy must be communicated to study subjects and their understanding confirmed.
• Men who partner with a woman of childbearing potential, unless they agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through to the end of study. Permitted methods for preventing pregnancy must be communicated to study subjects and their understanding confirmed.
• Females who are pregnant or are currently breastfeeding.
• Known positive status for HIV.
• Clinically active hepatitis B or C.
• Diagnosis of another malignancy unless free of disease for at least three years following therapy with curative intent. Patients with early-stage basal cell or squamous cell skin cancer, cervical intraepithelial neoplasia, cervical carcinoma in situ or superficial bladder cancer may be eligible to participate at the Investigator's discretion.
• Any acute active infection.
• Cardiac dysrhythmias requiring treatment, or prolongation of the QTc (Fridericia) interval to \>450 msec for males or \>470 msec for females at pre-study screening, unless attributable to pre-existing bundle branch block.
• Presence of \>= Grade 2 peripheral neuropathy.
• Uncontrolled congestive heart failure (New York Heart Association Classification 3 or 4), uncontrolled or unstable angina, myocardial infarction, cerebrovascular accident, or pulmonary embolism within 3 months prior to initiation of study drug.
• Uncontrolled inter current illness or any concurrent condition that, in the Investigator's opinion, would jeopardize the safety of the patient or compliance with the protocol.

Sponsors & Collaborators

• Sierra Oncology LLC - a GSK company: lead

Study Sites (6)

Stanford Cancer Center

Stanford, California, 94305-5821, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

The Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Ayalew Tefferi, MD

  Mayo Clinic

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: November 5, 2010
• First Posted: November 8, 2010
• Study Start: November 1, 2010
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: February 4, 2019

Record last verified: 2019-01

Locations

CA (2); US (3); AU (1)