A Study of Anagrelide Controlled Release (GALE-401) in Patients With High Platelet Counts Due to Bone Marrow Disorders

NCT02125318 | Completed Phase 2

• 1 other identifier: GALE-401-201
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 11

Brief Summary

Anagrelide is a drug that has been shown to slow down how fast platelets are made in the bone marrow, and has been approved by the FDA for treating high platelets counts in patients with bone marrow disorders. Anagrelide Controlled Release ("CR") is a new preparation of anagrelide that is made to dissolve more slowly than currently marketed versions of this drug. Because of this, the anagrelide is taken up into the blood more slowly. Researchers think that this slower release of the drug could help to lower side effects that might be caused by high blood levels when the drug dissolves as quickly as it does with the currently marketed product. The main purposes of this study are to see how well Anagrelide CR can control platelet counts in patients with high platelet levels, to see what kind of side effects it causes, and to measure blood levels of the drug.

Conditions

Thrombocytosis; Myeloproliferative Neoplasms

Keywords

myeloproliferative neoplasm; chronic myelogenous leukemia; polycythemia vera; primary myelofibrosis; essential thrombocythemia; anagrelide; thrombocytosis; GALE-401

Outcome Measures

Primary Outcomes (1)

• Platelet Response

  The primary efficacy endpoint will be the proportion of subjects who achieve a platelet response (complete or partial response), with response defined according to the following criteria: * Complete response (CR): platelet count of ≤400 x 10e9/L maintained for at least 4 weeks * Partial response (PR): a platelet count of ≤600 x 10e9/L or a ≥50% reduction from baseline and maintenance of the reduction for at least 4 weeks * Nonresponse: failure to meet CR or PR criteria

  Up to 24 weeks

Secondary Outcomes (2)

• Number of subjects with adverse events

  Throughout study treatment (expected average of 12 months)

• Plasma concentrations of anagrelide

  Up to 13 weeks

Study Arms (1)

Anagrelide CR (GALE-401)

EXPERIMENTAL

Drug: Anagrelide CR

Interventions

Anagrelide CR DRUG

Starting dose of 0.5 mg b.i.d. (1.0 mg/day) titrated at weekly intervals, on an individual basis, to achieve the lowest dose required to achieve and maintain a target platelet count of 150 - 400 x 10e9/L, tolerability permitting. The dose will be increased at weekly intervals in steps not exceeding 0.5 mg/day; the rate of dose titration may be reduced (i.e., up to once every 2 weeks) at the discretion of the Investigator.

Also known as: GALE-401

Anagrelide CR (GALE-401)

Eligibility Criteria

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

You may qualify if:

• Provide written informed consent prior to any study specific procedure
• Male or female patients aged ≥ 18 years
• Diagnosis of a myeloproliferative neoplasm (i.e., chronic myelogenous leukemia (CML), polycythemia vera (PV), primary myelofibrosis (PMF), essential thrombocythemia (ET)) as determined by the treating physician, such as based on the 2008 World Health Organization (WHO) classification of myeloid malignancies
• Baseline platelet count ≥600 x 10e9/L as determined on two occasions at least 14 days apart prior to the first dose of study drug
• Requirement for platelet reduction therapy as assessed by the Investigator
• Currently not receiving therapy specifically intended to reduce platelet counts
• For patients with ET, prior platelet lowering therapy (e.g., hydroxyurea, anagrelide or interferon) may not be administered within 2 weeks prior to the first dose of study drug.
• For patients with MPN diagnoses other than ET, concurrent anti-MPN treatment is permitted provided that the treatment has been administered at stable doses for at least 4 weeks prior to the first dose of study drug. Examples of permitted medications include but are not limited to hydroxyurea for PV, ruxolitinib for MF, and imatinib for CML. All patients must have discontinued anagrelide at least 2 weeks prior to the first dose of study drug.
• EXCEPTION: busulfan, melphalan and phosphate P-32 must have been discontinued at least 4 weeks prior to the first dose of study drug.
• Adequate hepatic function defined as bilirubin ≤1.5 x ULN, INR ≤1.5 x ULN, albumin \>3.5 g/dL, ALT \< 3.0 x ULN, AST \< 3.0 x ULN
• If female, must be of non-childbearing potential, i.e. post- menopausal (defined as \> 12 months since last menstrual period) or surgically sterilized (i.e. tubal ligation or hysterectomy at least 6 months prior to screening) or, if of childbearing potential, must not be pregnant or nursing
• Males and females of child bearing must agree to use an acceptable form of birth control until 28 days following the last dose of study drug

You may not qualify if:

• Other MPN diagnoses not specifically included above: Chronic neutrophilic leukemia, chronic eosinophilic leukemia, mastocytosis, and unclassifiable MPNs
• Previously found to be refractory to anagrelide therapy (i.e., failure to achieve a platelet count \<600 x 10e9/L for reasons other than anagrelide-related toxicity)
• History of coronary artery disease requiring a revascularization procedure within 3 months prior to screening
• Left bundle branch block or sustained ventricular tachycardia (\>30 seconds) evident on 12-lead ECG at screening
• Tachycardia defined as resting heart rate \>100 bpm at screening
• Unstable angina (characterized by increasingly frequent episodes with modest exertion or at rest, worsening severity, or prolonged duration) within 3 months prior to screening
• Transient ischemic attack (TIA) or stroke within 3 months prior to screening
• Unstable or clinically significant concurrent medical condition that would, in the opinion of the Investigator, jeopardize the safety of a subject and/or their compliance with the protocol.
• Current alcohol or drug abuse, or a significant medical condition that, in the opinion of the Investigator, may impair compliance with the requirements of the protocol
• History of allergic hypersensitivity to anagrelide or any component of its formulations
• Administration of Type 3 phosphodiesterase (PDE3) inhibitors (e.g., inamrinone, cilostazol, milrinone) within 2 weeks prior to initiating study treatment
• Administration of any investigational product within 4 weeks prior to initiating study treatment
• History of intolerance of other PDE3 inhibitors

Sponsors & Collaborators

• Galena Biopharma, Inc.: lead

Study Sites (11)

East Valley Hematology and Oncology Medical Group

Burbank, California, 91505, United States

Location

California Cancer Associates for Research & Excellence (cCARE)

Encinitas, California, 92024, United States

Location

California Cancer Associates for Research & Excellence (cCARE)

Escondido, California, 92025, United States

Location

California Cancer Associates For Research and Excellence

Fresno, California, 93720, United States

Location

Innovative Medical Research of South Florida, Inc.

Aventura, Florida, 33180, United States

Location

Cancer Center of Kansas

Wichita, Kansas, 67214, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

Location

Gettysburg Cancer Center

Hillsdale, Pennsylvania, 17325, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Cancer Care Centers of South Texas

New Braunfels, Texas, 78130, United States

Location

Cancer Care Centers of South Texas

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Thrombocytosis; Myeloproliferative Disorders; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Polycythemia Vera; Primary Myelofibrosis; Thrombocythemia, Essential

Condition Hierarchy (Ancestors)

Blood Platelet Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Blood Coagulation Disorders; Hemorrhagic Disorders

Study Design

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

Study Record Dates

• First Submitted: April 23, 2014
• First Posted: April 29, 2014
• Study Start: May 1, 2014
• Primary Completion: May 1, 2016
• Study Completion: May 1, 2016
• Last Updated: February 27, 2017

Record last verified: 2017-02

Locations

US (11)