Phase II Hedgehog Inhibitor for Myelodysplastic Syndrome (MDS)

NCT01842646

Last updated date
Study Location
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612, United States
Contact
1-800-718-1021

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Myelodysplastic Syndrome (MDS), Chronic Myelomonocytic Leukemia (CMML)
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- 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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- 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.

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Myelodysplastic Syndrome (MDS), Chronic Myelomonocytic Leukemia (CMML)Phase II Hedgehog Inhibitor for Myelodysplastic Syndrome (MDS)
NCT01842646
  1. Tampa, Florida
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE Phase II Hedgehog Inhibitor for Myelodysplastic Syndrome (MDS)
Official Title  ICMJE A Phase II Study Evaluating the Oral Smoothened Inhibitor PF-04449913 in Patients With Myelodysplastic Syndrome (MDS)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Myelodysplastic Syndrome (MDS)
  • Chronic Myelomonocytic Leukemia (CMML)
Intervention  ICMJE Drug: 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.
Other Names:
  • Oral Hedgehog Inhibitor
  • Smoothened (SMO) Inhibitor
Study Arms  ICMJE Experimental: 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.
Intervention: Drug: PF-04449913
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: April 25, 2013)
35
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2020
Actual Primary Completion Date January 31, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01842646
Other Study ID Numbers  ICMJE MCC-17302
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party H. Lee Moffitt Cancer Center and Research Institute
Study Sponsor  ICMJE H. Lee Moffitt Cancer Center and Research Institute
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Principal Investigator:Jeffrey Lancet, M.D.H. Lee Moffitt Cancer Center and Research Institute
PRS Account H. Lee Moffitt Cancer Center and Research Institute
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP