Clinical Trial: Filgrastim, Cladribine, Cytarabine, and Mitoxantrone With Sorafenib Tosylate in Treating Patients With Newly-Diagnosed, Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

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

Official Title: Addition of Sorafenib to G-CSF, Cladribine, Cytarabine, and Mitoxantrone (G-CLAM) in Adults With Newly-Diagnosed Acute Myeloid Leukemia (AML) Independent of FLT3-ITD Status: A Phase 1/2 Study

Brief Summary: This phase I/II trial studies the side effects and best dose of filgrastim (granulocyte colony-stimulating factor [G-CSF]), cladribine, cytarabine, and mitoxantrone hydrochloride, when given together with sorafenib tosylate and to see how well they work in treating patients with newly-diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome (likely to be more aggressive). Drugs used in chemotherapy, such as filgrastim, cladribine, cytarabine, and mitoxantrone hydrochloride work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Sorafenib tosylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving filgrastim, cladribine, cytarabine, and mitoxantrone hydrochloride together with sorafenib tosylate may kill more cancer cells.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To assess the maximum tolerated dose (MTD) of sorafenib (sorafenib tosylate) used in combination with dose-intensified mitoxantrone (mitoxantrone hydrochloride) as part of the G-CSF, cladribine, cytarabine and mitoxantrone hydrochloride (G-CLAM) regimen in adults with newly-diagnosed acute myeloid leukemia (AML)/high-risk myelodysplastic syndromes (MDS). (Phase 1)

II. To determine if the addition of sorafenib to G-CLAM improves the rate of minimal residual disease negative (MRDneg) complete response (CR) compared with our center's historical control of G-CLAM alone in adults with newly-diagnosed AML/high-risk MDS. (Phase 2)

SECONDARY OBJECTIVES:

I. To estimate rates of CR, overall response rate (ORR), overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS) after the addition of sorafenib to G-CLAM in patients with newly-diagnosed AML/high-risk MDS.

II. To describe the toxicity profile and safety (rate of adverse events) of sorafenib in combination with G-CLAM.

III. To assess the feasibility of incorporating quality of life (QOL), cost and healthcare resource utilization endpoints in to a phase 1/2 clinical trial for newly diagnosed AML.

IV. To investigate, within the limits of a phase 1/2 trial, the impact of study treatment and response on quality of life, cost, and healthcare resource utilization for patients with AML undergoing intensive chemotherapy.

OUTLINE: This is a phase I, dose-escalation study of mitoxantrone and sorafenib tosylate followed by a phase II study.

Sponsor: University of Washington

Current Primary Outcome:

  • Maximum tolerated dose (MTD), defined as the highest dose studied in which the incidence of dose-limiting toxicity is < 33% assuming at least 6 patients have been treated at this dose (Phase I) [ Time Frame: 28 days ]
  • Minimal residual disease negative (MRDneg) complete response (CR) rate (Phase II) [ Time Frame: 56 days (2 courses of induction chemotherapy) ]


Original Primary Outcome:

  • Minimal residual disease negative (MRDneg) complete response (CR) rate (Phase II) [ Time Frame: 56 days (2 courses of induction chemotherapy) ]
  • Maximum tolerated dose (MTD), defined as the highest dose studied in which the incidence of dose-limiting toxicity is < 33% assuming at least 6 patients have been treated at this dose (Phase I) [ Time Frame: 28 days ]


Current Secondary Outcome:

  • Complete response (CR) [ Time Frame: Up to 5 years ]
  • Costs, obtained by cost records [ Time Frame: Up to 5 years ]
    Will be recorded and summarized using descriptive methods including boxplots, histograms, and statistical summary measures (medians, means, standard deviation, N, and proportions).
  • Event-free survival (EFS) [ Time Frame: Up to 5 years ]
  • Incidence of toxicity using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 [ Time Frame: Up to 5 years ]
  • Mean duration of hospital stays [ Time Frame: Up to 5 years ]
  • Number of blood product transfusions received [ Time Frame: Up to 5 years ]
  • Number of clinic visits [ Time Frame: Up to 5 years ]
  • Number of days in hospital [ Time Frame: Up to 5 years ]
  • Number of days in the intensive care unit [ Time Frame: Up to 5 years ]
  • Number of days requiring antibiotic use [ Time Frame: Up to 5 years ]
  • Number of episodes of febrile neutropenia [ Time Frame: Up to 5 years ]
  • Number of hospital admissions [ Time Frame: Up to 5 years ]
  • Number of visits to the emergency department [ Time Frame: Up to 5 years ]
  • Overall response rate (ORR) [ Time Frame: Up to 5 years ]
  • Overall survival (OS) [ Time Frame: Up to 5 years ]
  • Quality of life (QOL) scores, assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 [ Time Frame: Up to 5 years ]
    Will be recorded and summarized using descriptive methods including boxplots, histograms, and statistical summary measures (medians, means, standard deviation, N, and proportions).
  • Relapse-free survival (RFS) [ Time Frame: Up to 5 years ]


Original Secondary Outcome:

  • Costs, obtained by cost records [ Time Frame: Up to 5 years ]
    This will be a composite measure. Will be recorded and summarized using descriptive methods including boxplots, histograms, and statistical summary measures (medians, means, standard deviation, N, and proportions).
  • Complete response (CR) [ Time Frame: Up to 5 years ]
  • Event-free survival (EFS) [ Time Frame: Up to 5 years ]
  • Incidence of toxicity using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 [ Time Frame: Up to 5 years ]
  • Overall response rate (ORR) [ Time Frame: Up to 5 years ]
  • Overall survival (OS) [ Time Frame: Up to 5 years ]
  • Quality of life (QOL) scores, assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 [ Time Frame: Up to 5 years ]
    Will be recorded and summarized using descriptive methods including boxplots, histograms, and statistical summary measures (medians, means, standard deviation, N, and proportions).
  • Relapse-free survival (RFS) [ Time Frame: Up to 5 years ]
  • Number of days in hospital [ Time Frame: Up to 5 years ]
  • Number of hospital admissions [ Time Frame: Up to 5 years ]
  • Mean duration of hospital stays [ Time Frame: Up to 5 years ]
  • Number of days in the intensive care unit [ Time Frame: Up to 5 years ]
  • Number of blood product transfusions received [ Time Frame: Up to 5 years ]
  • Number of episodes of febrile neutropenia [ Time Frame: Up to 5 years ]
  • Number of days requiring antibiotic use [ Time Frame: Up to 5 years ]
  • Number of visits to the emergency department [ Time Frame: Up to 5 years ]
  • Number of clinic visits [ Time Frame: Up to 5 years ]


Information By: University of Washington

Dates:
Date Received: March 14, 2016
Date Started: December 2016
Date Completion:
Last Updated: March 15, 2017
Last Verified: March 2017