Last updated on July 2019

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


Brief description of study

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 Study Description

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.

INDUCTION: Patients receive mitoxantrone hydrochloride intravenously (IV) over 60 minutes on days 1-3 and sorafenib tosylate orally (PO) twice daily (BID) on days 10-19 in the absence of disease progression or unacceptable toxicity. Patients also receive filgrastim subcutaneously (SC) once daily (QD) on days 0-5, cladribine IV QD over 2 hours on days 1-5, and cytarabine IV QD over 2 hours on days 1-5 in the absence of disease progression or unacceptable toxicity. Patients achieving partial remission (including MRD positive [pos] CR, CR with incomplete platelet recovery [CRp], and CR with incomplete count recovery [CRi]) or persistent AML may receive up to 2 cycles of induction therapy per the discretion of the treating physician.

POST-REMISSION: Patients receive sorafenib tosylate PO BID on days 8-27 or 3 days prior to next cycle of treatment, whichever occurs first. Patients also receive filgrastim subcutaneously SC QD on days 0-5, cladribine IV QD over 2 hours on days 1-5, and cytarabine IV QD over 2 hours on days 1-5 in the absence of disease progression or unacceptable toxicity. Patients achieving MRDneg CR may receive up to 4 cycles of post-remission therapy. Patients achieving disease response (MRDpos CR, CRi/CRp, or persistent disease) may receive up to two induction cycles and 1 cycle of post-remission therapy with mitoxantrone hydrochloride omitted in cycle 3. If they then enter MRDneg CR, they can proceed with up to a total of 4 cycles of post-remission therapy.

MAINTENANCE THERAPY: Patients achieving MRDneg CR may receive maintenance therapy of sorafenib tosylate PO BID for up to 1 year.

After completion of study treatment, patients are followed up every 3 months for up to 5 years.

Clinical Study Identifier: NCT02728050

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Recruitment Status: Open


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