Know Cancer

or
forgot password

A Phase 2 Study of PF-04449913 for the Treatment of Acute Leukemia Patients With High Risk of Post-Allogeneic Stem Cell Transplantation Relapse


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Adult Acute Lymphoblastic Leukemia in Remission, Adult Acute Myeloid Leukemia in Remission, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Adult Acute Myeloid Leukemia

Thank you

Trial Information

A Phase 2 Study of PF-04449913 for the Treatment of Acute Leukemia Patients With High Risk of Post-Allogeneic Stem Cell Transplantation Relapse


Disease relapse is the most common cause of death after allogeneic stem cell transplantation
for acute leukemia. Patients at high risk for relapse may benefit from a novel,
biologically rational therapeutic intervention to prevent this outcome. PF-04449913 is a
small molecule inhibitor of the hedgehog (Hh) pathway that inhibits the protein Smoothened
(SMO). Aberrant Hh signaling may contribute to the survival and expansion of the leukemia
stem cell, and inhibiting the Hh pathway can eliminate these cells. Therefore, targeting Hh
may be a logical intervention in the post-transplantation setting for those with high risk
of relapse. The investigators propose a phase 2 study of PF-04449913 in post-allogeneic
stem cell transplantation patients at high risk of relapse.

This is an open label, phase 2 study employing PF-04449913 in acute leukemia patients who
received allogeneic stem cell transplantation and are at high risk of relapse. Patients will
receive consecutive 28-day cycles of PF-04449913 at 100 mg/day, beginning on
post-transplantation day 80 +/- 10 days, after their routine post-transplant bone marrow
biopsy. Treatment will continue for up to one year or until they experience toxicity or
disease relapse. Seventeen patients will be required for an 80% power to detect a 30%
difference in one-year relapse free survival.


Inclusion Criteria:



- World Health Organization (WHO)-confirmed acute myeloid leukemia (AML) or acute
lymphoblastic leukemia (ALL)

- Eastern Cooperative Oncology Group (ECOG) performance status =< 2

- Life expectancy > 2 months

- Serum/urine pregnancy test (for females of childbearing potential) that is negative
within 72 hours prior to initiation of first dose of treatment (a patient is of
childbearing potential if, in the opinion of the investigator, she is biologically
capable of having children and is sexually active)

- Female patients of childbearing potential and sexually active males and female
partners of childbearing potential must agree to use a highly effective method of
contraception throughout the study and for at least 90 days after the last dose of
assigned treatment

- Recipient of a fully myeloablative or non-myeloablative allogeneic hematopoietic stem
cell transplant (HSCT) using one of the following conditioning regimens:

- Myeloablative: Cyclophosphamide 120 mg/kg + total body irradiation (TBI) 12 Gray (Gy)
or busulfan 12.8 mg/kg + cyclophosphamide 120 mg/kg for matched unrelated or related
donors

- Non-myeloablative: 2-3 Gy TBI + 90 mg/m^2 fludarabine for matched unrelated or
related donors; 2 Gy TBI + cyclophosphamide 50 mg/kg + fludarabine 200 mg/m2 for cord
blood donors

- Between days 70 and 90 post transplant at time of initiation of study drug

- Stable engraftment, as defined by absolute neutrophil count (ANC) >= 1000/mm^3 and
platelets 20,000/mm^3

- High risk of relapse after fully myeloablative HSCT, defined as:

- Any level of minimal residual disease (MRD) on a bone marrow aspirate or peripheral
blood sample, at any routine measurement post-HSCT

- Any patient entering into HSCT with MRD by flow cytometry

- Any patient entering into HSCT with cytogenetic abnormalities as measured by
metaphase cytogenetics or fluorescent in situ hybridization (FISH) probes

- Any patient entering into HSCT without a morphological remission

- High risk of relapse after non-myeloablative allogeneic HSCT, defined as:

- Relapse risk score > 0

- Any patient entering into HSCT with MRD by flow cytometry

- Any patient entering into HSCT with cytogenetic abnormalities as measured by
metaphase cytogenetics or FISH probes

- Any patient entering into HSCT without a morphological remission

Exclusion Criteria:

- Concomitant treatment with other anti-neoplastic agents

- Use of any other experimental drug or therapy within 28 days of baseline

- Inability to swallow or absorb drug

- Active uncontrolled opportunistic infection at time of study drug dosing

- New York Heart Association class III or IV heart failure

- Corrected QT (QTc) interval > 470 msec

- Patients with congenital long QT syndrome

- Any history of ventricular fibrillation or torsades de pointes

- Bradycardia defined as heart rate (HR) < 50 bpm

- Right bundle branch block and left anterior hemiblock (bifascicular block)

- Patients with myocardial infarction < 6 months prior to starting study drug

- Unstable angina pectoris

- Cardiac arrhythmias with rapid ventricular response (defined as heart rate greater
than 100 beats/minute)

- Uncontrolled psychiatric illness that would limit compliance with requirements

- Known human immunodeficiency virus (HIV) infection

- Grade III/IV acute graft-versus-host disease (GVHD)

- Current use or anticipated need for food or drugs that are known strong/moderate
cytochrome P450 3A4 (CYP3A4) inhibitors or strong CYP3A4 inducers, including their
administration within 7-days prior to study entry

- Recipient of myeloablative cord blood transplant, as there is a lower association
with relapse

- Other medical or psychiatric illness or organ dysfunction or laboratory abnormality
which in the opinion of the investigator would compromise the patient's safety or
interfere with data interpretation

- Pregnant or lactating females

- Either creatinine >=1.5 institutional upper limit of normal (ULN) or creatinine
clearance =< 60 mL/min

- Total bilirubin > 2 x institutional ULN (unless documented Gilbert's syndrome)

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) > 3 x
institutional ULN

- ANC < 1000/mm^3

- Platelet count < 20,000/mm^3

Type of Study:

Interventional

Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Relapse-free survival

Outcome Description:

Kaplan-Meier estimates will be used to measure relapse-free survival

Outcome Time Frame:

At 1 year

Safety Issue:

No

Principal Investigator

Daniel A Pollyea, MD, MS

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Colorado, Denver

Authority:

United States: Food and Drug Administration

Study ID:

12-1558.cc

NCT ID:

NCT01841333

Start Date:

April 2013

Completion Date:

April 2019

Related Keywords:

  • Adult Acute Lymphoblastic Leukemia in Remission
  • Adult Acute Myeloid Leukemia in Remission
  • Recurrent Adult Acute Lymphoblastic Leukemia
  • Recurrent Adult Acute Myeloid Leukemia
  • Lymphoblastic leukemia in remission
  • Myeloid leukemia in remission
  • Recurrent lymphoblastic leukemia
  • Recurrent myeloid leukemia
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid

Name

Location

University of Colorado Cancer CenterDenver, Colorado  80262