Phase II Hedgehog Inhibitor for Myelodysplastic Syndrome (MDS)
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|ClinicalTrials.gov Identifier: NCT01842646|
Recruitment Status : Active, not recruiting
First Posted : April 29, 2013
Results First Posted : March 14, 2017
Last Update Posted : September 26, 2018
|Condition or disease||Intervention/treatment||Phase|
|Myelodysplastic Syndrome (MDS) Chronic Myelomonocytic Leukemia (CMML)||Drug: PF-04449913||Phase 2|
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 :||Interventional (Clinical Trial)|
|Actual Enrollment :||35 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study Evaluating the Oral Smoothened Inhibitor PF-04449913 in Patients With Myelodysplastic Syndrome (MDS)|
|Actual Study Start Date :||August 29, 2013|
|Actual Primary Completion Date :||January 31, 2016|
|Estimated Study Completion Date :||March 2020|
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.
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.
- Overall International Working Group (IWG) 2006 Response Rate [ Time Frame: Up to 2 years, 4 months ]Response recorded from the start of the treatment until disease progression/recurrence. All responses must last for at least 8 weeks. Complete Remission (CR): Bone marrow: ≤ 5% myeloblasts with normal maturation of all cell lines, Persistent dysplasia will be noted, Peripheral blood: Hemoglobin ≥ 11 g/dL, Platelets ≥ 100 x 10^9/L, Neutrophils ≥ 1.0 x 10^9/L, Blasts 0% ; Partial Remission (PR): All CR criteria if abnormal before treatment, except: Bone marrow blasts decreased by ≥ 50% over pretreatment but still > 5%, Cellularity and morphology not relevant; Marrow CR or Hematological Improvement (HI): Bone marrow: ≤ 5% myeloblasts and decrease by ≥ 50% over pretreatment Peripheral blood: if HI responses, they will be noted in addition to marrow CR. Further investigation of PF-04449913 would not be warranted if it produced an overall response rate (CR + PR + marrow CR+HI) of 10% or less (p0), and would be warranted if it produced an overall response rate of 30% or more (p1).
- Median Overall Survival (OS) [ Time Frame: Up to 2 years, 4 months ]To estimate the overall survival of patients with refractory/relapsed myelodysplastic Syndrome (MDS) and chronic myelo-monocytic leukemia (CMML) treated with PF-0444913. Overall survival will be defined as the time period between the date of the first dose of drug until the time of death.
- Median Event Free Survival [ Time Frame: Up to 2 years, 4 months ]To estimate the event-free survival of patients of this population. Event-free survival will be defined as the date of the first dose of study drug until failure or death from any cause.
- Median Time to Transformation to Acute Myeloid Leukemia (AML) [ Time Frame: Up to 2 years, 4 months ]To estimate the time to transformation to AML in patients with <20% blasts. In patients with less than 20% blasts, the time to transformation to AML will be defined as the date of the first dose of drug until either the percentage of bone marrow blasts or the percentage of peripheral blasts exceeds 20%, whichever is first.
- Treatment Emergent Adverse Events [ Time Frame: 2 years, 4 months ]Treatment emergent adverse events occurring in equal to or more than 10% of participants.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01842646
|United States, Florida|
|H. Lee Moffitt Cancer Center and Research Institute|
|Tampa, Florida, United States, 33612|
|Principal Investigator:||Jeffrey Lancet, M.D.||H. Lee Moffitt Cancer Center and Research Institute|