Clinical Trial: Filgrastim, Cladribine, Cytarabine, and Mitoxantrone Hydrochloride in Treating Patients With Newly Diagnosed or Relapsed/Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes

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

Official Title: A Phase 1/2 Trial of G-CSF, Cladribine, Cytarabine, and Dose-Escalated Mitoxantrone (G-CLAM) in Adults With Newly Diagnosed or Relapsed/Refractory Acute Myeloid Leukemia (AML) or High-Risk Myelodyspla

Brief Summary: This phase I/II trial studies the side effects and best dose of mitoxantrone hydrochloride when given together with filgrastim, cladribine, and cytarabine and to see how well they work in treating patients with acute myeloid leukemia or high-risk myelodysplastic syndromes that is newly diagnosed, has returned, or does not respond to treatment. 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.

Detailed Summary:

PRIMARY OBJECTIVES:

I. Estimate the maximum tolerated dose (MTD) of dose-intensified mitoxantrone hydrochloride (mitoxantrone) as part of the filgrastim (G-CSF), cladribine, cytarabine, mitoxantrone hydrochloride (G-CLAM) regimen separately for adults with newly diagnosed acute myeloid leukemia (AML) and those with relapsed/refractory AML receiving first or greater salvage therapy.

SECONDARY OBJECTIVES:

I. To determine, within the limits of a phase 1/2 study, disease response and duration of remission separately for patients with newly diagnosed and relapsed/refractory AML.

II. To describe, within the limits of a phase 1/2 study, the toxicity profile of the study regimen separately for patients with newly diagnosed and relapsed/refractory AML.

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

INDUCTION CHEMOTHERAPY (G-CLAM): Patients receive G-CLAM chemotherapy comprising filgrastim subcutaneously (SC) daily on days 0-5, mitoxantrone hydrochloride intravenously (IV) over 60 minutes on days 1-3, cladribine IV over 2 hours daily on days 1-5, and cytarabine IV over 2 hours daily on days 1-5. Patients achieving complete remission with incomplete peripheral blood count recovery (CRi), partial remission, or persistent disease may receive a second course of induction chemotherapy. Patients achieving complete remission (CR) or CR with incomplete platelet count recovery (CRp) may continue on to Consolidation Chemotherapy.

CONSOLIDATION CHEMOTHERAPY (G-CLA): Beginning within 6 weeks of achieving CR/CRp/CRi, patients receive G-CLA
Sponsor: Fred Hutchinson Cancer Research Center

Current Primary Outcome:

  • Maximum tolerated dose of mitoxantrone, defined as the highest dose studied in which the incidence of dose-limiting toxicity is < 33%, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (Phase I) [ Time Frame: Up to day 45 after start of induction chemotherapy ]
  • Minimal residual disease negative complete remission rate in patients with newly diagnosed disease (Phase II) [ Time Frame: Up to day 45 after start of second course of induction chemotherapy ]


Original Primary Outcome:

  • MTD of mitoxantrone hydrochloride, defined as the highest dose studied in which the incidence of dose-limiting toxicity is < 33%, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (Phase I) [ Time Frame: Day 28 ]
  • Remission rate (CR and CRp) of this regimen (Phase II) [ Time Frame: Up to 5 years ]


Current Secondary Outcome:

  • Overall survival rate (Phase II expansion cohort) [ Time Frame: 12 months ]
    In addition to the formal test of 12-month overall survival, the entire survival curve will be estimated using the Kaplan-Meier method. Overall survival of this cohort will be compared to a historical cohort treated with standard of care using Cox regression methods.
  • Remission rate (complete remission and complete remission with incomplete platelet count recovery) of this regimen in patients with relapsed/refractory disease (Phase II) [ Time Frame: Up to 5 years ]


Original Secondary Outcome:

Information By: Fred Hutchinson Cancer Research Center

Dates:
Date Received: January 22, 2014
Date Started: January 23, 2014
Date Completion:
Last Updated: April 28, 2017
Last Verified: April 2017