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

Sponsor

Galena Biopharma, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT02125318

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

1.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Thrombocytosis Myeloproliferative Neoplasms	Drug: Anagrelide CR	Phase 2

Detailed Description

This is an open-label, single-arm, multicenter, Phase 2 study of anagrelide CR in subjects with an MPN-related thrombocytosis. Eligible subjects will include those who have not been previously treated for thrombocytosis or have not received platelet-lowering therapy for at least 2 weeks prior to study treatment. Each subject will receive anagrelide CR at a starting dose of 0.5 mg b.i.d. (1.0 mg/day), and is anticipated to continue study treatment for at least 24 weeks. Subjects who have achieved clinical benefit in the opinion of the Investigator and who are tolerating the study drug may continue study treatment until they develop unacceptable toxicity or other discontinuation criteria have been met.

The primary efficacy endpoint will be the proportion of subjects who achieve a platelet response (CR or PR). The safety and tolerability of study treatment will be assessed by the frequency and severity of adverse events as determined by NCI Common Terminology Criteria for Adverse Events (CTCAE) v 4.03. The PK profile of anagrelide CR will be assessed at the initial (0.5mg b.i.d.) and final titrated dose levels.

Study Design

Study Type:

Interventional

Actual Enrollment :

18 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 2, Open Label Efficacy and Safety Study of Anagrelide Controlled Release (CR) in Subjects With Thrombocytosis Secondary to Essential Thrombocythemia and Other Myeloproliferative Neoplasms (MPN)

Study Start Date :

May 1, 2014

Actual Primary Completion Date :

May 1, 2016

Actual Study Completion Date :

May 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Anagrelide CR (GALE-401)	Drug: Anagrelide CR 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. Other Names: GALE-401

Arm

Intervention/Treatment

Experimental: Anagrelide CR (GALE-401)

Drug: Anagrelide CR

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.

Other Names:

GALE-401

Outcome Measures

Primary Outcome Measures

Platelet Response [Up to 24 weeks]
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

Secondary Outcome Measures

Number of subjects with adverse events [Throughout study treatment (expected average of 12 months)]
Frequency and severity of adverse events as determined by NCI CTCAE (v 4.03).
Plasma concentrations of anagrelide [Up to 13 weeks]
Monitor anagrelide levels during dose titration and assess pharmacokinetic profile at starting and final dose levels.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	East Valley Hematology and Oncology Medical Group	Burbank	California	United States	91505
2	California Cancer Associates for Research & Excellence (cCARE)	Encinitas	California	United States	92024
3	California Cancer Associates for Research & Excellence (cCARE)	Escondido	California	United States	92025
4	California Cancer Associates For Research and Excellence	Fresno	California	United States	93720
5	Innovative Medical Research of South Florida, Inc.	Aventura	Florida	United States	33180
6	Cancer Center of Kansas	Wichita	Kansas	United States	67214
7	Wake Forest Baptist Health	Winston-Salem	North Carolina	United States	27157
8	Gettysburg Cancer Center	Gettysburgh	Pennsylvania	United States	17325
9	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
10	Cancer Care Centers of South Texas	New Braunfels	Texas	United States	78130
11	Cancer Care Centers of South Texas	San Antonio	Texas	United States	78229