Clinical trial NCT00623870: A Study of RO5045337 [RG7112] in Patients With Hematologic Neoplasms.
Official title: An Open Label Study to Investigate the Maximum Tolerated Dose of RO5045337 in Patients With Acute Myelogenous Leukemia (AML), Acute Lymphocytic Leukemia (ALL), Chronic Myelogenous Leukemia (CML) in Blast Phase, or Refractory Chronic Lymphocytic Leukemia/Small Cell Lymphocytic Lymphoma (CLL / SCLL)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hematologic Neoplasms
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2008-02-26
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will determine the maximum tolerated dose of RO5045337 and the optimal associated 4 weekly dosing schedule of RO5045337, administered as monotherapy in patients with hematologic neoplasms. A first cohort of patients will receive the starting dose of 20mg/m2/day orally, once daily for 10 days in each 28 day cycle. Subsequent cohorts of patients will receive dose escalations, and possible changes in dosing schedule, based on tolerability and pharmacokinetic knowledge gained from prior treatment cohorts. Different formulations of RO5045337 will be tested and the food effect evaluated. The anticipated time on study treatment is until disease progression or intolerable toxicity.


Eligibility criteria: Inclusion Criteria:

* Adult patients, \>=18 years of age
* Acute myeloid leukemia, acute lymphocytic leukemia, chronic myelogenous leukemia in blast phase, refractory chronic lymphocytic leukemia/small cell lymphocytic lymphoma
* Relapsed or refractory to approved therapies, or no viable alternative therapy available
* ECOG performance status of 0-2

Exclusion Criteria:

* Patients receiving any other agent or therapy to treat their malignancy
* Pre-existing gastrointestinal disorders which may interfere with absorption of drugs
* Clinically significant cardiovascular disease
* Pregnant or lactating women
* HIV-positive patients receiving combination antiretroviral therapy
* Amendment J and onward for patients in the food effect evaluation and for all subsequent patients if dosing with a high fat/high calorie meal is found to be optimal: Patients with allergies to any ingredient in the defined liquid supplement and/or inability to tolerate a high fat/high calorie meal twice daily on scheduled RO5045337 dosing days

Primary outcomes:
measure: Maximum tolerated dose/Dose-limiting toxicities
timeFrame: approximately 4.5 years
measure: Safety: Incidence of adverse events
timeFrame: approximately 4.5 years
measure: Comparison of daily versus twice daily dosing: Incidence of adverse events
timeFrame: approximately 4.5 years
Secondary outcomes:
measure: Pharmacokinetics: Blood/Urine concentrations
timeFrame: Pre- and post-dose multiple sampling Days 1+2/Days 1+10 Cycle 1, post-dose sampling Days 11+15 Cycle 1, pre-dose Days 1+2 Cycle 2
measure: Pharmacodynamics: Blood leukemia cells/MIC-1 protein level/CD33+CD34 markers
timeFrame: Pre- and post-dose Days 1+10 Cycle 1, pre-dose Day 2 Cycle 1, Days 1+2 Cycle 2
measure: Clinical response: Clinical/hematologic malignancy assessments
timeFrame: approximately 4.5 years
Other outcomes:
Locations:
city: Duarte
country: United States
state: California
city: New Brunswick
country: United States
state: New Jersey
city: New York
country: United States
state: New York
city: Houston
country: United States
state: Texas
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Bologna
country: Italy
state: Emilia-Romagna
city: Roma
country: Italy
state: Lazio
city: Glasgow
country: United Kingdom
city: Leeds
country: United Kingdom
city: Oxford
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: