Study of Dasatinib and All-Trans Retinoic Acid for Relapsed/Refractory and/or Elderly Patients With Acute Myelogenous Leukemia (AML) or Myelodysplastic Syndrome

Phase 1

Completed

• Conditions: Acute Myelogenous Leukemia; Myelodysplastic Syndrome
• Interventions: Drug: dasatinib (SPRYCEL); Drug: all trans retinoic acid (VESANOID)

• Registration Number: NCT00892190
• Lead Sponsor: University of Pittsburgh

Brief Summary

This is an open label, prospective, single institution dose-escalation study. The patient population includes non-induction candidate elderly patients with AML or MDS and/or patients with high-risk or relapsed/refractory AML or MDS. Five dose cohorts will be evaluated using a fixed dose of ATRA in combination with an escalating dose of dasatinib. The investigators will treat with an escalating dose of dasatinib from 70mg to 140mg daily. Dose escalation will proceed in a standard 3+3 fashion. A de-escalation to a 50 mg total daily dose of dasatinib is planned if DLT is greater than or equal to 33% is observed at the first dose level. Once the MTD for the combination of the drugs has been established, up to 6 additional patients will be enrolled at the MTD level to obtain additional safety information about the combination and to allow for preliminary laboratory correlate analysis.

Detailed Description

Primary Objective:

1. To determine the safety and tolerability of the combination of dasatinib and ATRA in relapsed or elderly, non-induction candidate acute myelogenous leukemia (AML) or MDS patients and to identify the maximally tolerated dose (MTD), dose-limiting toxicities (DLT).

Secondary Objectives:

1. To determine the pharmacokinetic (PK) profiles of dasatinib and ATRA when administered as combination therapy for patients with AML or MDS

2. To determine if the combination therapy of dasatinib and ATRA promotes differentiation of AML or MDS .

Study Timeline

• Study First Submitted: 2009-04-30
• Study First Submitted QC: 2009-05-01
• Study First Posted: 2009-05-04
• Study Start: 2011-04
• Primary Completion: 2016-01
• Status Verified: 2016-02
• Study Completion: 2016-02
• Last Update Submitted: 2016-02-09
• Last Update Posted: 2016-02-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 9

Inclusion Criteria

Not provided

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Exclusion Criteria

Prisoners, or subjects who are involuntarily incarcerated. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
dasatinib (SPRYCEL) and all trans retinoic acid (VESANOID)	dasatinib (SPRYCEL)	Dasatinib DL0 - 50 mg every 24 hours DL1 (START)- 70 mg every 24 hours DL2 - 100 mg every 24 hours DL3 - 140 mg every 24 hours ATRA 22.5mg/m2 every 12 hours
dasatinib (SPRYCEL) and all trans retinoic acid (VESANOID)	all trans retinoic acid (VESANOID)	Dasatinib DL0 - 50 mg every 24 hours DL1 (START)- 70 mg every 24 hours DL2 - 100 mg every 24 hours DL3 - 140 mg every 24 hours ATRA 22.5mg/m2 every 12 hours

Primary Outcome Measures

Name	Time	Method
To determine the MTD and DLTs of dasatinib in combination with ATRA given the proposed dose escalation plan.	1.5 years

Secondary Outcome Measures

Name	Time	Method
Assessment of Differentiation. Bone marrow biopsies and aspirates will be obtained pre-treatment, on day 14, and day 28. These will be subjected to morphologic, cytochemical, and routine flow cytometric analyses.	1.5 years
Assess treatment effects on SFK (Src family kinase) activation and expression of RARA target genes.	1.5 years
PK parameters including peak concentration (Cmax),Tmax, Cmin, the area under the curve (AUC), volume of distribution, clearance terms, elimination rate constant, and elimination half-life (t1/2) will be analyzed.	1.5 years

Trial Locations

Locations (1)

University of Pittsburgh Cancer Institute - Hillman Cancer Center; 🇺🇸 Pittsburgh, Pennsylvania, United States