A Study of RO5045337 [RG7112] in Patients With Hematologic Neoplasms.

Hematologic Neoplasms Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00623870
• Other study ID #: NO21279
• Status: Completed
• Phase: Phase 1
• First received: February 18, 2008
• Last updated: November 1, 2016
• Start date: May 2008
• Est. completion date: November 2012

Study information

• Verified date: November 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 116
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hematologic Neoplasms
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Neoplasms

Intervention

Drug:
• RO5045337
Multiple ascending doses

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Canada,  Italy,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose/Dose-limiting toxicities		approximately 4.5 years	No
Primary	Safety: Incidence of adverse events		approximately 4.5 years	No
Primary	Comparison of daily versus twice daily dosing: Incidence of adverse events		approximately 4.5 years	No
Secondary	Pharmacokinetics: Blood/Urine concentrations		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	No
Secondary	Pharmacodynamics: Blood leukemia cells/MIC-1 protein level/CD33+CD34 markers		Pre- and post-dose Days 1+10 Cycle 1, pre-dose Day 2 Cycle 1, Days 1+2 Cycle 2	No
Secondary	Clinical response: Clinical/hematologic malignancy assessments		approximately 4.5 years	No