Phase II Hedgehog Inhibitor for Myelodysplastic Syndrome (MDS)

NCT ID: NCT01842646

Last Updated: 2021-06-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-29
• Study Completion Date: 2021-06-10

Brief Summary

This study is being done to see how safe an investigational drug is and test how well it will work to help people with refractory/relapsed myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML).

Detailed Description

The main purpose of this study is to see whether the participant's disease responds favorably to the investigational drug, PF-04449913.

Post treatment Phase: After coming off of active treatment study drug (PF-04449913), participants will be followed monthly for survival only. No other data will be captured during this time.

Conditions

Myelodysplastic Syndrome (MDS); Chronic Myelomonocytic Leukemia (CMML)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PF-04449913 Treatment

Treatment will be administered on an outpatient basis. All patients will be treated with an oral dose PF-04449913 at 100 mg daily in 4-week cycles for a total of 4 cycles. Patients who demonstrate no evidence of progressive disease (i.e. stable disease or better) may continue on treatment until disease progression or loss of response, limiting toxicity, or death.

Group Type: EXPERIMENTAL

PF-04449913

Intervention Type: DRUG

Patients will be enrolled according to a two-step study design. Twenty patients will be enrolled in the first stage. All patients will be given a daily oral dose of PF-0444913 100 mg for up to 4 cycles, with an optional continuation phase. Dose escalation to 200 mg will be provided for patients who do not have at least hematologic improvement following 2 cycles, and dose reduction to 50 mg will be permitted for patients with significant toxicity. If at least 2 patients respond in the initial stage, and additional 15 patients will be enrolled in the second stage.

Interventions

PF-04449913

Patients will be enrolled according to a two-step study design. Twenty patients will be enrolled in the first stage. All patients will be given a daily oral dose of PF-0444913 100 mg for up to 4 cycles, with an optional continuation phase. Dose escalation to 200 mg will be provided for patients who do not have at least hematologic improvement following 2 cycles, and dose reduction to 50 mg will be permitted for patients with significant toxicity. If at least 2 patients respond in the initial stage, and additional 15 patients will be enrolled in the second stage.

Intervention Type: DRUG

Other Intervention Names

Oral Hedgehog Inhibitor; Smoothened (SMO) Inhibitor

Eligibility Criteria

Inclusion Criteria

• Must have a pathologically confirmed diagnosis by World Health Organization (WHO) Criteria of MDS, CMML, or acute myeloid leukemia (AML) (except acute promyelocytic leukemia) with < 30% bone marrow blasts (RAEB-t by French American British criteria)
• Hypomethylating agent (azacitidine and/or decitabine) failure, defined as lack of response, disease progression, loss of response, or intolerance as deemed by the study investigator
• Adequate renal function, as evidenced by a serum creatinine ≤ 2 times the institutional upper limit of normal
• Adequate hepatic function, as evidenced by a serum bilirubin < 2 times the institutional upper limit of normal and an aspartic transaminase (AST) and alanine transaminase (ALT) < 2 times the institutional upper limit of normal. Indirect hyperbilirubinemia due to Gilbert's disease or hemolysis is permitted.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Patients with a history of prior therapy with another investigational agent within 4 weeks of the first planned dose of PF-0444913
• Patients may not be receiving any other investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to PF-04449913
• Prior therapy with another hedgehog inhibitor
• Concurrent use of any other agent for MDS, CMML, or AML. Growth factor use with epoetin, darbepoetin, or granulocyte colony-stimulating factor must be terminated at least 2 weeks before initiation of study treatment.
• Any uncontrolled concurrent illness that would, in the opinion of the investigator, limit compliance with study requirements
• Second malignancy requiring active therapy
• A prolonged corrected QT interval (QTc) of ≥480 ms interval on electrocardiogram
• History of metastatic cancer diagnosed less than 2 years prior to the first planned dose of PF-0444913
• Uncontrolled concurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study because PF-04449913 is smoothened inhibitor with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with PF-04449913. Breastfeeding should be discontinued if the mother is treated with PF-04449913.
• Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy. Therefore, HIV-positive patients receiving combination antiretroviral therapy are excluded from the study because of possible pharmacokinetic interactions with PF-04449913.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

H. Lee Moffitt Cancer Center and Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jeffrey Lancet, M.D.

Role: PRINCIPAL_INVESTIGATOR

H. Lee Moffitt Cancer Center and Research Institute

Locations

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Countries

United States

Other Identifiers

MCC-17302

Identifier Type: -

Identifier Source: org_study_id