Clinical Trial: Bortezomib and Sorafenib Tosylate in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase III Randomized Trial for Patients With De Novo AML Using Bortezomib and Sorafenib (NSC# 681239, NSC# 724772) for Patients With High Allelic Ratio FLT3/ITD

Brief Summary: This randomized phase III trial studies how well bortezomib and sorafenib tosylate work in treating patients with newly diagnosed acute myeloid leukemia. Bortezomib and sorafenib tosylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving bortezomib and sorafenib tosylate together with combination chemotherapy may be an effective treatment for acute myeloid leukemia.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To compare event-free survival (EFS) and overall survival (OS) in patients with de novo acute myeloid leukemia (AML) without high allelic ratio fms-like tyrosine kinase (FLT3)/internal tandem duplications (ITD)+ mutations who are randomized to standard therapy versus bortezomib/standard combination therapy.

II. To determine the feasibility of combining bortezomib with standard chemotherapy in patients with de novo AML.

III. To compare the OS and EFS of high-risk patients treated with intensive Induction II with historical controls from AAML03P1 and AAML0531.

IV. To determine the feasibility of administering sorafenib (sorafenib tosylate) with standard chemotherapy and in a one year maintenance phase in patients with de novo high allelic ratio FLT3/ITD+ AML.

SECONDARY OBJECTIVES:

I. To assess the anti-leukemic activity of sorafenib in patients with de novo high allelic ratio FLT3/ITD+ AML.

II. To compare the percentage of patients converting from positive minimal residual disease (MRD) to negative MRD after Intensive Induction II with historical controls from AAML03P1 and AAML0531.

III. To compare OS, disease-free survival (DFS), cumulative incidence of relapse, and treatment-related mortality from end of Intensification I between patients allocated to best allogenic donor stem cell transplant (SCT) and comparable patients on AAML0531 who did not receive allogenic donor SCT.

IV. To compare OS, DFS, cumulative incidence of relapse, treatment-related mortality
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • EFS (Arm C, Cohort 1) [ Time Frame: From the time on study to induction failure, relapse or death, up to 11 years ]
  • EFS (Arm C, Cohort 2) [ Time Frame: From the time on study to induction failure, relapse or death, up to 11 years ]
  • EFS (Arm C, Cohort 3) [ Time Frame: From the time on study to induction failure, relapse or death, up to 11 years ]
  • EFS for patients without high allelic ratio FLT3/ITD+ mutations [ Time Frame: From the time on study to induction failure, relapse or death, up to 11 years ]


Original Primary Outcome: Event-free survival

Current Secondary Outcome:

  • Bortezomib pharmacokinetic plasma concentration-time profiles [ Time Frame: Day 8 of Induction II ]
  • OS (Arm C, Cohort 1) [ Time Frame: Up to 11 years ]
  • OS (Arm C, Cohort 2) [ Time Frame: Up to 11 years ]
  • OS (Arm C, Cohort 3) [ Time Frame: Up to 11 years ]
  • OS for patients without high allelic ratio FLT3/ITD+ mutations [ Time Frame: Up to 11 years ]
  • Parent-reported questionnaire scores [ Time Frame: At 4 months following start of SCT or intensification II of chemotherapy ]
  • Proportion of high risk children without HR FLT3/ITD+ converting from positive MRD at end of Induction I to negative MRD at the end of Induction II [ Time Frame: Up to 8 weeks ]
  • Proportion of patients experiencing grade 3 or higher non-hematologic toxicities and infections assessed by Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0) [ Time Frame: Up to 11 years ]
  • Relapse rate assessed by bone marrow analysis for leukemic blasts [ Time Frame: Up to 11 years ]
  • Serum concentrations of GVHD biomarkers [ Time Frame: Up to day 28 after SCT ]
  • Shortening fraction/ejection fraction percentages and change over time [ Time Frame: Baseline to up to 11 years ]
  • Systemic exposure of sorafenib tosylate and N-oxide metabolite for each course of induction and intensification (CL, Vd, time to maximum concentration [Tmax1/2, area under curve [AUC]) [ Time Frame: Up to 4 months ]


Original Secondary Outcome:

  • Overall survival
  • Remission rate after 1 and 2 courses of therapy
  • Proportion of patients dying in each course of therapy
  • Course duration
  • Length of hospitalization
  • Time to blood count recovery
  • Relapse rate
  • Treatment-related mortality
  • Frequency of toxicities, including infectious and cardiac complications


Information By: National Cancer Institute (NCI)

Dates:
Date Received: June 10, 2011
Date Started: June 2011
Date Completion:
Last Updated: May 19, 2017
Last Verified: May 2017