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

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

Official Title: Randomized Phase 1 Study of Sequential ("Primed") vs. Concurrent Decitabine in Combination With G-CSF, Cladribine, Cytarabine, and Mitoxantrone (G-CLAM) in Adults With Newly Diagnosed or Rel

Brief Summary: This randomized phase I trial studies the side effects and best dose of decitabine when given together with filgrastim, cladribine, cytarabine, and mitoxantrone hydrochloride in treating patients with acute myeloid leukemia or myelodysplastic syndrome that is newly diagnosed, has come back, or has not responded to treatment. Drugs used in chemotherapy, such as decitabine, 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. Colony-stimulating factors, such as filgrastim, may increase the production of blood cells and may help the immune system recover from the side effects of chemotherapy. Decitabine, filgrastim, cladribine, cytarabine, and mitoxantrone hydrochloride may work better in treating patients with acute myeloid leukemia and myelodysplastic syndrome.

Detailed Summary:

PRIMARY OBJECTIVES:

I. Estimate the maximum tolerated dose (MTD) of decitabine when used sequentially or concomitantly with filgrastim, cladribine, cytarabine, and mitoxantrone hydrochloride (G-CLAM) independently in patients with newly diagnosed or relapsed/refractory acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS).

SECONDARY OBJECTIVES:

I. Evaluate, within the limits of a phase I study, disease response and duration of remission.

II. Describe, within the limits of a phase I study, the toxicity profile of the study regimen.

III. Describe, within the limits of a phase I study, the impact of the study regimen on quality of life.

OUTLINE: This is a dose de-escalation study of decitabine. Patients are randomized to 1 of 2 groups.

GROUP I (PRIMED): Patients receive decitabine intravenously (IV) over 1 hour on days -14 to -5. Patients also receive filgrastim subcutaneously (SC) on days 0-5, cladribine IV over 2 hours on days 1-5, cytarabine IV over 2-4 hours on days 1-5 and mitoxantrone hydrochloride IV over 60 minutes on days 1-3.

GROUP II (CONCURRENT): Patients receive decitabine IV over 1 hour on days 1-10. Patients also receive filgrastim, cladribine, cytarabine, and mitoxantrone hydrochloride as in Group I.

In both groups, treatment repeats every 10 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION THERAPY: Beginning 6 weeks after achieving complete rem
Sponsor: Fred Hutchinson Cancer Research Center

Current Primary Outcome: Determination of Maximum Tolerated Dose (MTD) for decitabine when given together with G-CLAM determined by dose limiting toxicities (DLTs) evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 20 days ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Duration of Remission (CR/CRi) [ Time Frame: Up to 5 years ]
• Event-free survival [ Time Frame: Up to 5 years ]
  Survival endpoints will be summarized descriptively and categorized according to criteria recommended by International Working Groups.
• Overall survival [ Time Frame: Up to 5 years ]
  Survival endpoints will be summarized descriptively and categorized according to criteria recommended by International Working Groups.
• Quality of life assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) [ Time Frame: Baseline and up to 5 years ]
  The EORTC QLQ-C30 is a validated 30-item instrument that measures quality of life and includes five functional scales, three symptom scales, a global health scale, and six single items. Standardized scores for each scale and single-item measure range from 0 to 100, with higher scores representing better domain-specific QOL. A minimally clinically meaningful difference is considered to be 10 points based on established methods.
• Relapse-free survival [ Time Frame: Up to 5 years ]
  Survival endpoints will be summarized descriptively and categorized according to criteria recommended by International Working Groups.
• Remission (CR/CRi) [ Time Frame: Up to 5 years ]
  Remission status will be summarized descriptively and categorized according to criteria recommended by International Working Groups.

Original Secondary Outcome:

• Event-free survival [ Time Frame: Up to 5 years ]
  Survival endpoints will be summarized descriptively and categorized according to criteria recommended by International Working Groups.
• Overall survival [ Time Frame: Up to 5 years ]
  Survival endpoints will be summarized descriptively and categorized according to criteria recommended by International Working Groups.
• Quality of life assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) [ Time Frame: Up to 5 years ]
  The EORTC QLQ-C30 is a validated 30-item instrument that measures quality of life and includes five functional scales, three symptom scales, a global health scale, and six single items. Standardized scores for each scale and single-item measure range from 0 to 100, with higher scores representing better domain-specific QOL. A minimally clinically meaningful difference is considered to be 10 points based on established methods.
• Relapse-free survival [ Time Frame: Up to 5 years ]
  Survival endpoints will be summarized descriptively and categorized according to criteria recommended by International Working Groups.
• Remission (CR/CRi) [ Time Frame: Up to 5 years ]
  Remission status will be summarized descriptively and categorized according to criteria recommended by International Working Groups.
• Duration of Remission (CR/CRi) [ Time Frame: Up to 5 years ]

Dates:
Date Received: September 29, 2016
Date Started: November 2016
Date Completion:
Last Updated: January 5, 2017
Last Verified: January 2017