Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Rare Diseases

Syndrome

Leukemia

Preleukemia

Myelodysplastic Syndromes

Leukemia, Myelomonocytic, Chronic

Leukemia, Myelomonocytic, Juvenile

Neoplasms by Histologic Type

Hematologic Diseases

Bone Marrow Diseases

Precancerous Conditions

Leukemia, Myeloid

Myeloproliferative Disorders

Myelodysplastic-Myeloproliferative Diseases

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Chronic Myelomonocytic Leukemia

Juvenile Myelomonocytic Leukemia

Chronic Myeloproliferative Disorders

Myelodysplastic/myeloproliferative Disease

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.

PF-04449913

Jeffrey Lancet, M.D.

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).

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.

Phase II Hedgehog Inhibitor for Myelodysplastic Syndrome (MDS)

A Phase II Study Evaluating the Oral Smoothened Inhibitor PF-04449913 in Patients With Myelodysplastic Syndrome (MDS)

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).

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.

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 (disease progression) or death from any cause.

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 occurring in equal to or more than 10% of participants.

Pfizer

H. Lee Moffitt Cancer Center and Research Institute

Treatment to be administered on an outpatient basis. All participants to be treated with an oral dose PF-04449913 at 100 mg daily in 4-week cycles for a total of 4 cycles.

Experimental: PF-04449913 Treatment

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Dr. Jeffrey Lancet

Overall International Working Group (IWG) 2006 Response Rate

Median Overall Survival (OS)

Median Event Free Survival

NA- The median time to AML was not reached due to insufficient number of participants with events.

Median Time to Transformation to Acute Myeloid Leukemia (AML)

Grade 1-2 : Pain

Grade 1-2 : Dysgeusia

Grade 1-2 : Nausea

Grade 1-2 : Anorexia

Grade 1-2 : Skin/rash

Grade 1-2 : Oral mucositis

Grade 1-2 : AST elevated

Grade 1-2 : Alopecia

Grade 1-2 : ALT elevated

Grade 1-2 : Dizziness

Grade 1-2 : Dyspnea

Grade 1-2 : Infections

Grade 1-2 : Fatigue

Grade 1-2 : Diarrhea

Grade 1-2 : Constipation

Grade 1-2 : Fever

Grade 1-2 : Hyperkalemia

Grade 1-2 : Hyperglycemia

Grade 1-2 : Thrombocytopenia

Grade 1-2 : Headache

Grade 1-2 : Vomiting

Grade 3-4 : Pain

Grade 3-4 : Dysgeusia

Grade 3-4 : Nausea

Grade 3-4 : Anorexia

Grade 3-4 : Skin/rash

Grade 3-4 : Oral mucositis

Grade 3-4 : AST elevated

Grade 3-4 : Alopecia

Grade 3-4 : ALT elevated

Grade 3-4 : Dizziness

Grade 3-4 : Dyspnea

Grade 3-4 : Infections

Grade 3-4 : Fatigue

Grade 3-4 : Diarrhea

Grade 3-4 : Constipation

Grade 3-4 : Fever

Grade 3-4 : Hyperkalemia

Grade 3-4 : Hyperglycemia

Grade 3-4 : Thrombocytopenia

Grade 3-4 : Headache

Grade 3-4 : Vomiting

Number of Participants With Treatment Emergent Adverse Events

Overall Study

Spots Global Cancer Trial Database for Phase II Hedgehog Inhibitor for Myelodysplastic Syndrome (MDS)

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial