Efficacy and Safety of Simtuzumab in Adults With Primary, Post Polycythemia Vera or Post Essential Thrombocythemia Myelofibrosis

Gilead Sciences

Status and phase: Completed; Phase 2

Conditions: Myelofibrosis

Treatments: Drug: Simtuzumab; Drug: Ruxolitinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT01369498

AB0024-102

Details and patient eligibility

About

This study is to evaluate the efficacy and safety of simtuzumab (GS-6624) on bone marrow fibrosis either alone or in combination with ruxolitinib in participants with primary myelofibrosis (PMF) and post polycythemia vera or post essential thrombocythemia myelofibrosis (ET/PV MF).

The study is designed as a two-stage trial. In the stage 1, participants will be randomized into two cohorts to receive either 200 or 700 mg of study drug. In the stage 2, participants on ruxolitinib will be randomized to receive either 200 or 700 mg of study drug.

Enrollment: 54 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Must be diagnosed with PMF or post ET/PV MF with intermediate-1, intermediate-2 or high risk disease according to the international working group (IWG) prognostic scoring system, or if with low risk disease then with symptomatic splenomegaly that is ≥ 10 cm below left costal margin by physical exam.
• Must have adequate organ function as demonstrated by the following:
• Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤ 2.5x upper limit of normal (ULN), or ≤ 4x ULN (if upon judgment of the treating physician, it is believed to be due to extramedullary hematopoiesis [EMH] related to MF);
• Direct bilirubin ≤ 1.5 x ULN; or ≤ 2x ULN (if upon judgment of the treating physician, it is believed to be due to extramedullary hematopoiesis [EMH] related to MF);
• Serum creatinine ≤ 2.5 mg/dL.
• In Stage 2, participants must be on ruxolitinib for at least 8 weeks and on a stable dose for at least 4 weeks.
• Eastern cooperative oncology group (ECOG) performance status (PS) ≤ 2
• Treatment-related toxicities from prior therapies must have resolved to Grade ≤ 1
• Women of childbearing potential and men must agree to using one medically approved (ie, mechanical or pharmacological) contraceptive measure and have their partners agree to an additional barrier method of contraception for the duration of the study and for 90 days after the last administration of study drug. Definition of female of child bearing potential and a list of acceptable contraceptive methods for this study applies per protocol.

Exclusion criteria

• Any serious medical condition or psychiatric illness that would prevent, (as judged by the treating physician) the participant from signing the informed consent form or any condition, including the presence of laboratory abnormalities, which places the participant at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
• Pregnant or lactating.
• Known history of human immunodeficiency virus (HIV), hepatitis C, or hepatitis B.
• History or presence of any form of cancer within the 3 years prior to enrollment, with the exception of excised basal cell or squamous cell carcinoma of the skin, or cervical carcinoma in situ or breast carcinoma in situ that has been excised or resected completely and is without evidence of local recurrence or metastasis.
• Participation in an investigational drug or device trial within 2 weeks prior to study Day 1 or within 5 times the half-life of the investigational agent in the other clinical study, if known.
• Use of any cytotoxic chemotherapeutic agents (eg, hydroxyurea), corticosteroids (prednisone ≤ 10 mg/day or corticosteroid equivalent is allowed), or immune modulators (eg, thalidomide) within 2 weeks and interferon use within 4 weeks prior to study Day 1.
• Symptomatic congestive heart failure (New York Heart Association Classification > Class II), unstable angina, or unstable cardiac arrhythmia requiring medication.
• History of surgery within 2 weeks prior to enrollment or anticipated surgery during the study period.
• Any other condition that might reduce the chance of obtaining data required by the protocol or that might compromise the ability to give truly informed consent.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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54 participants in 4 patient groups

Simtuzumab 200 mg

Experimental group

Description:

Participants in Stage 1 of study will receive simtuzumab 200 mg for up to 24 weeks. Treatment could be continued if there is evidence of clinical benefit as judged by the treating physician.

Treatment:

Drug: Simtuzumab

Simtuzumab 700 mg

Experimental group

Description:

Participants in Stage 1 of study will receive simtuzumab 700 mg for up to 24 weeks. Treatment could be continued if there is evidence of clinical benefit as judged by the treating physician.

Treatment:

Drug: Simtuzumab

Simtuzumab 200 mg+Ruxolitinib

Experimental group

Description:

In Stage 2, participants on stable doses of ruxolitinib will receive simtuzumab 200 mg for at least 24 weeks. Treatment could be continued if there is evidence of clinical benefit as judged by the treating physician.

Treatment:

Drug: Ruxolitinib

Drug: Simtuzumab

Simtuzumab 700 mg+Ruxolitinib

Experimental group

Description:

In Stage 2, participants on stable doses of ruxolitinib will receive simtuzumab 700 mg for at least 24 weeks. Treatment could be continued if there is evidence of clinical benefit as judged by the treating physician.

Treatment:

Drug: Ruxolitinib

Drug: Simtuzumab