Filgrastim, Cladribine, Cytarabine, and Mitoxantrone Hydr... | NCT02044796

ID	Type	Description	Link
NCI-2013-02465	Registry Identifier	CTRP (Clinical Trial Reporting Program)
2734.00	Other Identifier	Fred Hutch/University of Washington Cancer Consortium
P30CA015704	U.S. NIH Grant/Contract		View source

Name	Class
National Cancer Institute (NCI)	NIH

Description Module

Detailed Description

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 comprising filgrastim SC on days 0-5, cladribine IV over 2 hours daily on days 1-5, and cytarabine IV over 2 hours daily on days 1-5. Treatment continues for up to 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically for up to 5 years.

Label	Type	Description	Intervention Names
Treatment (filgrastim, mitoxantrone, cladribine, cytarabine)	Experimental	INDUCTION CHEMOTHERAPY (G-CLAM): Patients receive G-CLAM chemotherapy comprising filgrastim SC daily on days 0-5, mitoxantrone hydrochloride 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 CRi, partial remission, or persistent disease may receive a second course of induction chemotherapy. Patients achieving CR or CRp may continue on to Consolidation Chemotherapy. CONSOLIDATION CHEMOTHERAPY (G-CLA): Beginning within 6 weeks of achieving CR/CRp/CRi, patients receive G-CLA comprising filgrastim SC on days 0-5, cladribine IV over 2 hours daily on days 1-5, and cytarabine IV over 2 hours daily on days 1-5. Treatment continues for up to 4 courses in the absence of disease progression or unacceptable toxicity.	Drug: Cladribine Drug: Cytarabine Biological: Filgrastim Other: Laboratory Biomarker Analysis Drug: Mitoxantrone Hydrochloride

Name	Type	Description	Arm Group Labels	Other Names
Cladribine	Drug	Given IV	Treatment (filgrastim, mitoxantrone, cladribine, cytarabine)

Measure	Description	Time Frame
Number of Participants With Dose Limiting Toxicities of Mitoxantrone (Phase I, Dose Level 4)	Defined as the highest dose studied in which the incidence of dose-limiting toxicity is < 33%, graded according to NCI Common Terminology Criteria for Adverse Events version 4.0	Up to day 45 after start of induction chemotherapy
Minimal Residual Disease Negative Complete Remission Rate in Patients With Newly Diagnosed Disease (Phase II)	Remission Rate defined as Recist Category of Complete Resposne (CR) Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size(<10 mm short axis).	Up to day 45 after start of second course of induction chemotherapy

Measure	Description	Time Frame
Overall Survival (Phase II)	Number of subjects that have survived	From date of randomization until the date of death from any cause, assessed up to 12 months
Remission Rate (Complete Remission and Complete Remission With Incomplete Platelet Count Recovery) of This Regimen in Patients With Relapsed/Refractory Disease (Phase II)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

For patients with newly diagnosed disease: diagnosis of "high-risk" myelodysplastic syndrome (MDS) (>= 10% blasts) or AML other than acute promyelocytic leukemia (APL) with t(15;17)(q22;q12) or variants according to the 2008 World Health Organization (WHO) classification; for patients with relapsed/refractory disease: prior diagnosis of "high-risk" MDS or non-APL AML, with relapsed/refractory disease according to standard criteria requiring first or subsequent salvage therapy; patients with biphenotypic AML are eligible
Outside diagnostic material is acceptable as long as peripheral blood and/or bone marrow slides are reviewed at the study institution; flow cytometric analysis of peripheral blood and/or bone marrow should be performed according to institutional practice guidelines
For patients with relapsed/refractory disease: patients with prior autologous or allogeneic hematopoietic cell transplantation (HCT) for MDS/AML are eligible if relapse occurs provided symptoms of graft-versus host disease are well controlled with stable use of immunosuppressive agents
Treatment-related mortality (TRM) score =< 6.9 as calculated with simplified model
The use of hydroxyurea prior to study registration is allowed; patients with symptoms/signs of hyperleukocytosis or white blood cell (WBC) > 100,000/uL can be treated with leukapheresis or may receive up to 2 doses of cytarabine (up to 500 mg/m^2/dose) prior to enrollment
For patients with relapsed/refractory disease: patients may have previously received chemotherapy with a mitoxantrone- or cladribine-based regimen for MDS or AML; if that patient has received G-CLAM before and has been sensitive to this regimen, eligibility will be determined on a case-by-case basis by the study principal investigator (PI)
Should be off any active systemic therapy for AML with the exception of hydroxyurea for at least 14 days prior to study registration unless patient has rapidly progressive disease, and all grade 2-4 non-hematologic toxicities should have resolved
Bilirubin =< 2.5 x institutional upper limit of normal (IULN) unless elevation is thought to be due to hepatic infiltration by AML, Gilbert's syndrome, or hemolysis (assessed within 14 days prior to study day 0)
Serum creatinine =< 2.0 mg/dL (assessed within 14 days prior to study day 0)
Left ventricular ejection fraction >= 45%, assessed within 3 months prior to study day 0, e.g. by multi gated acquisition scan (MUGA) scan or echocardiography, or other appropriate diagnostic modality and no clinical evidence of congestive heart failure; if the patient had anthracycline-based therapy since the most recent cardiac assessment, cardiac evaluation should be repeated if there is clinical or radiographic suspicion of cardiac dysfunction, or if the previous cardiac assessment was abnormal
Women of childbearing potential and men must agree to use adequate contraception
Provide written informed consent

Exclusion Criteria:

Myeloid blast crisis of chronic myeloid leukemia (CML), unless patient is not considered candidate for tyrosine kinase inhibitor treatment
Concomitant illness associated with a likely survival of < 1 year
Active systemic fungal, bacterial, viral, or other infection, unless disease is under treatment with anti-microbials and/or controlled or stable (e.g. if specific, effective therapy is not available/feasible or desired [e.g. chronic viral hepatitis, human immunodeficiency virus (HIV)]); patient needs to be clinically stable as defined as being afebrile and hemodynamically stable for 24 hours; patients with fever thought to be likely secondary to leukemia are eligible
Known hypersensitivity to any study drug
Pregnancy or lactation
Treatment with any other investigational agent

Name	Affiliation	Role
Roland Walter	Fred Hutch/University of Washington Cancer Consortium	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Fred Hutch/University of Washington Cancer Consortium		Seattle	Washington	98109	United States

ID	Title	Description
FG000	Newly Diagnosed Group Mitoxantrone Hydrochloride 12 mg/m^2	INDUCTION CHEMOTHERAPY (G-CLAM): Patients receive G-CLAM chemotherapy comprising filgrastim SC daily on days 0-5, mitoxantrone hydrochloride 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 CRi, partial remission, or persistent disease may receive a second course of induction chemotherapy. Patients achieving CR or CRp may continue on to Consolidation Chemotherapy. CONSOLIDATION CHEMOTHERAPY (G-CLA): Beginning within 6 weeks of achieving CR/CRp/CRi, patients receive G-CLA comprising filgrastim SC on days 0-5, cladribine IV over 2 hours daily on days 1-5, and cytarabine IV over 2 hours daily on days 1-5. Treatment continues for up to 4 courses in the absence of disease progression or unacceptable toxicity. Cladribine: Given IV Cytarabine: Given IV Filgrastim: Given SC Laboratory Biomarker Analysis: Correlative studies Mitoxantrone Hydrochloride: Given IV

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP_ICF	Yes	Yes	Yes	Study Protocol, Statistical Analysis Plan, and Informed Consent Form	Apr 17, 2017

ID	Title	Description
BG000	Newly Diagnosed	INDUCTION CHEMOTHERAPY (G-CLAM): Patients receive G-CLAM chemotherapy comprising filgrastim SC daily on days 0-5, mitoxantrone hydrochloride 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 CRi, partial remission, or persistent disease may receive a second course of induction chemotherapy. Patients achieving CR or CRp may continue on to Consolidation Chemotherapy. CONSOLIDATION CHEMOTHERAPY (G-CLA): Beginning within 6 weeks of achieving CR/CRp/CRi, patients receive G-CLA comprising filgrastim SC on days 0-5, cladribine IV over 2 hours daily on days 1-5, and cytarabine IV over 2 hours daily on days 1-5. Treatment continues for up to 4 courses in the absence of disease progression or unacceptable toxicity. Cladribine: Given IV Cytarabine: Given IV
BG001	Relapsed/Refractory Group	INDUCTION CHEMOTHERAPY (G-CLAM): Patients receive G-CLAM chemotherapy comprising filgrastim SC daily on days 0-5, mitoxantrone hydrochloride 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 CRi, partial remission, or persistent disease may receive a second course of induction chemotherapy. Patients achieving CR or CRp may continue on to Consolidation Chemotherapy. CONSOLIDATION CHEMOTHERAPY (G-CLA): Beginning within 6 weeks of achieving CR/CRp/CRi, patients receive G-CLA comprising filgrastim SC on days 0-5, cladribine IV over 2 hours daily on days 1-5, and cytarabine IV over 2 hours daily on days 1-5. Treatment continues for up to 4 courses in the absence of disease progression or unacceptable toxicity. Cladribine: Given IV Cytarabine: Given IV
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG000139 BG00160 BG002199

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With Dose Limiting Toxicities of Mitoxantrone (Phase I, Dose Level 4)

Defined as the highest dose studied in which the incidence of dose-limiting toxicity is < 33%, graded according to NCI Common Terminology Criteria for Adverse Events version 4.0

Posted

Count of Participants

Participants

Up to day 45 after start of induction chemotherapy

ID	Title	Description
OG000	Newly Diagnosed Group	INDUCTION CHEMOTHERAPY (G-CLAM): Patients receive G-CLAM chemotherapy comprising filgrastim SC daily on days 0-5, mitoxantrone hydrochloride 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 CRi, partial remission, or persistent disease may receive a second course of induction chemotherapy. Patients achieving CR or CRp may continue on to Consolidation Chemotherapy. CONSOLIDATION CHEMOTHERAPY (G-CLA): Beginning within 6 weeks of achieving CR/CRp/CRi, patients receive G-CLA comprising filgrastim SC on days 0-5, cladribine IV over 2 hours daily on days 1-5, and cytarabine IV over 2 hours daily on days 1-5. Treatment continues for up to 4 courses in the absence of disease progression or unacceptable toxicity. Cladribine: Given IV Cytarabine: Given IV Filgrastim: Given SC Laboratory Biomarker Analysis: Correlative studies Mitoxantrone Hydrochloride: Given IV
OG001	Relapsed/Refractory Group	INDUCTION CHEMOTHERAPY (G-CLAM): Patients receive G-CLAM chemotherapy comprising filgrastim SC daily on days 0-5, mitoxantrone hydrochloride 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 CRi, partial remission, or persistent disease may receive a second course of induction chemotherapy. Patients achieving CR or CRp may continue on to Consolidation Chemotherapy. CONSOLIDATION CHEMOTHERAPY (G-CLA): Beginning within 6 weeks of achieving CR/CRp/CRi, patients receive G-CLA comprising filgrastim SC on days 0-5, cladribine IV over 2 hours daily on days 1-5, and cytarabine IV over 2 hours daily on days 1-5. Treatment continues for up to 4 courses in the absence of disease progression or unacceptable toxicity. Cladribine: Given IV Cytarabine: Given IV Filgrastim: Given SC Laboratory Biomarker Analysis: Correlative studies Mitoxantrone Hydrochloride: Given IV

Units	Counts
Participants	OG0006 OG0014

Title

Denominators

Categories

Title	Measurements
	OG0001 OG0012

Primary

Minimal Residual Disease Negative Complete Remission Rate in Patients With Newly Diagnosed Disease (Phase II)

Remission Rate defined as Recist Category of Complete Resposne (CR) Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size(<10 mm short axis).

Posted

Count of Participants

Participants

Up to day 45 after start of second course of induction chemotherapy

ID	Title	Description
OG000	Newly Diagnosed Group	INDUCTION CHEMOTHERAPY (G-CLAM): Patients receive G-CLAM chemotherapy comprising filgrastim SC daily on days 0-5, mitoxantrone hydrochloride 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 CRi, partial remission, or persistent disease may receive a second course of induction chemotherapy. Patients achieving CR or CRp may continue on to Consolidation Chemotherapy. CONSOLIDATION CHEMOTHERAPY (G-CLA): Beginning within 6 weeks of achieving CR/CRp/CRi, patients receive G-CLA comprising filgrastim SC on days 0-5, cladribine IV over 2 hours daily on days 1-5, and cytarabine IV over 2 hours daily on days 1-5. Treatment continues for up to 4 courses in the absence of disease progression or unacceptable toxicity. Cladribine: Given IV Cytarabine: Given IV Filgrastim: Given SC Laboratory Biomarker Analysis: Correlative studies Mitoxantrone Hydrochloride: Given IV
OG001	Relapsed/Refractory	INDUCTION CHEMOTHERAPY (G-CLAM): Patients receive G-CLAM chemotherapy comprising filgrastim SC daily on days 0-5, mitoxantrone hydrochloride 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 CRi, partial remission, or persistent disease may receive a second course of induction chemotherapy. Patients achieving CR or CRp may continue on to Consolidation Chemotherapy. CONSOLIDATION CHEMOTHERAPY (G-CLA): Beginning within 6 weeks of achieving CR/CRp/CRi, patients receive G-CLA comprising filgrastim SC on days 0-5, cladribine IV over 2 hours daily on days 1-5, and cytarabine IV over 2 hours daily on days 1-5. Treatment continues for up to 4 courses in the absence of disease progression or unacceptable toxicity. Cladribine: Given IV Cytarabine: Given IV Filgrastim: Given SC Laboratory Biomarker Analysis: Correlative studies Mitoxantrone Hydrochloride: Given IV

Secondary

Overall Survival (Phase II)

Number of subjects that have survived

Posted

Number

Participants

From date of randomization until the date of death from any cause, assessed up to 12 months

ID	Title	Description
OG000	Phase 2 Newly Diagnosed Group 18 mg/m^2	INDUCTION CHEMOTHERAPY (G-CLAM): Patients receive G-CLAM chemotherapy comprising filgrastim SC daily on days 0-5, mitoxantrone hydrochloride 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 CRi, partial remission, or persistent disease may receive a second course of induction chemotherapy. Patients achieving CR or CRp may continue on to Consolidation Chemotherapy. CONSOLIDATION CHEMOTHERAPY (G-CLA): Beginning within 6 weeks of achieving CR/CRp/CRi, patients receive G-CLA comprising filgrastim SC on days 0-5, cladribine IV over 2 hours daily on days 1-5, and cytarabine IV over 2 hours daily on days 1-5. Treatment continues for up to 4 courses in the absence of disease progression or unacceptable toxicity. Cladribine: Given IV Cytarabine: Given IV Filgrastim: Given SC Laboratory Biomarker Analysis: Correlative studies Mitoxantrone Hydrochloride: Given IV
OG001	Phase 2 Relapsed/Refractory Group 16 mg/m^2	INDUCTION CHEMOTHERAPY (G-CLAM): Patients receive G-CLAM chemotherapy comprising filgrastim SC daily on days 0-5, mitoxantrone hydrochloride 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 CRi, partial remission, or persistent disease may receive a second course of induction chemotherapy. Patients achieving CR or CRp may continue on to Consolidation Chemotherapy. CONSOLIDATION CHEMOTHERAPY (G-CLA): Beginning within 6 weeks of achieving CR/CRp/CRi, patients receive G-CLA comprising filgrastim SC on days 0-5, cladribine IV over 2 hours daily on days 1-5, and cytarabine IV over 2 hours daily on days 1-5. Treatment continues for up to 4 courses in the absence of disease progression or unacceptable toxicity. Cladribine: Given IV Cytarabine: Given IV Filgrastim: Given SC Laboratory Biomarker Analysis: Correlative studies Mitoxantrone Hydrochloride: Given IV

Secondary

Remission Rate (Complete Remission and Complete Remission With Incomplete Platelet Count Recovery) of This Regimen in Patients With Relapsed/Refractory Disease (Phase II)

Per the protocol, the 6 patients enrolled in the Phase 1 portion and treated at the MTD dose (16 mg/m^2) were included in the analysis of the Phase 2 remission rate.

Posted

Count of Participants

Participants

Up to 5 years

ID	Title	Description
OG000	Phase 2 Relapsed/Refractory Group 16 mg/m^2	INDUCTION CHEMOTHERAPY (G-CLAM): Patients receive G-CLAM chemotherapy comprising filgrastim SC daily on days 0-5, mitoxantrone hydrochloride 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 CRi, partial remission, or persistent disease may receive a second course of induction chemotherapy. Patients achieving CR or CRp may continue on to Consolidation Chemotherapy. CONSOLIDATION CHEMOTHERAPY (G-CLA): Beginning within 6 weeks of achieving CR/CRp/CRi, patients receive G-CLA comprising filgrastim SC on days 0-5, cladribine IV over 2 hours daily on days 1-5, and cytarabine IV over 2 hours daily on days 1-5. Treatment continues for up to 4 courses in the absence of disease progression or unacceptable toxicity. Cladribine: Given IV Cytarabine: Given IV Filgrastim: Given SC Laboratory Biomarker Analysis: Correlative studies Mitoxantrone Hydrochloride: Given IV

Units	Counts

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Newly Diagnosed Group Mitoxantrone Hydrochloride 12 mg/m^2	INDUCTION CHEMOTHERAPY (G-CLAM): Patients receive G-CLAM chemotherapy comprising filgrastim SC daily on days 0-5, mitoxantrone hydrochloride 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 CRi, partial remission, or persistent disease may receive a second course of induction chemotherapy. Patients achieving CR or CRp may continue on to Consolidation Chemotherapy. CONSOLIDATION CHEMOTHERAPY (G-CLA): Beginning within 6 weeks of achieving CR/CRp/CRi, patients receive G-CLA comprising filgrastim SC on days 0-5, cladribine IV over 2 hours daily on days 1-5, and cytarabine IV over 2 hours daily on days 1-5. Treatment continues for up to 4 courses in the absence of disease progression or unacceptable toxicity. Cladribine: Given IV Cytarabine: Given IV Filgrastim: Given SC Laboratory Biomarker Analysis: Correlative studies Mitoxantrone Hydrochloride: Given IV	0	9	9	8	9
EG001	Newly Diagnosed Group Mitoxantrone Hydrochloride 14 mg/m^2	INDUCTION CHEMOTHERAPY (G-CLAM): Patients receive G-CLAM chemotherapy comprising filgrastim SC daily on days 0-5, mitoxantrone hydrochloride 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 CRi, partial remission, or persistent disease may receive a second course of induction chemotherapy. Patients achieving CR or CRp may continue on to Consolidation Chemotherapy. CONSOLIDATION CHEMOTHERAPY (G-CLA): Beginning within 6 weeks of achieving CR/CRp/CRi, patients receive G-CLA comprising filgrastim SC on days 0-5, cladribine IV over 2 hours daily on days 1-5, and cytarabine IV over 2 hours daily on days 1-5. Treatment continues for up to 4 courses in the absence of disease progression or unacceptable toxicity. Cladribine: Given IV Cytarabine: Given IV Filgrastim: Given SC Laboratory Biomarker Analysis: Correlative studies Mitoxantrone Hydrochloride: Given IV	2	9	9	8	9
EG002	Newly Diagnosed Group Mitoxantrone Hydrochloride 16 mg/m^2	INDUCTION CHEMOTHERAPY (G-CLAM): Patients receive G-CLAM chemotherapy comprising filgrastim SC daily on days 0-5, mitoxantrone hydrochloride 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 CRi, partial remission, or persistent disease may receive a second course of induction chemotherapy. Patients achieving CR or CRp may continue on to Consolidation Chemotherapy. CONSOLIDATION CHEMOTHERAPY (G-CLA): Beginning within 6 weeks of achieving CR/CRp/CRi, patients receive G-CLA comprising filgrastim SC on days 0-5, cladribine IV over 2 hours daily on days 1-5, and cytarabine IV over 2 hours daily on days 1-5. Treatment continues for up to 4 courses in the absence of disease progression or unacceptable toxicity. Cladribine: Given IV Cytarabine: Given IV Filgrastim: Given SC Laboratory Biomarker Analysis: Correlative studies Mitoxantrone Hydrochloride: Given IV	2	9	9	9	9
EG003	Newly Diagnosed Group Mitoxantrone Hydrochloride 18 mg/m^2	INDUCTION CHEMOTHERAPY (G-CLAM): Patients receive G-CLAM chemotherapy comprising filgrastim SC daily on days 0-5, mitoxantrone hydrochloride 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 CRi, partial remission, or persistent disease may receive a second course of induction chemotherapy. Patients achieving CR or CRp may continue on to Consolidation Chemotherapy. CONSOLIDATION CHEMOTHERAPY (G-CLA): Beginning within 6 weeks of achieving CR/CRp/CRi, patients receive G-CLA comprising filgrastim SC on days 0-5, cladribine IV over 2 hours daily on days 1-5, and cytarabine IV over 2 hours daily on days 1-5. Treatment continues for up to 4 courses in the absence of disease progression or unacceptable toxicity. Cladribine: Given IV Cytarabine: Given IV Filgrastim: Given SC Laboratory Biomarker Analysis: Correlative studies Mitoxantrone Hydrochloride: Given IV	1	6	6	6	6
EG004	Relapsed/Refractory Group Mitoxantrone Hydrochloride 12 mg/m^2	INDUCTION CHEMOTHERAPY (G-CLAM): Patients receive G-CLAM chemotherapy comprising filgrastim SC daily on days 0-5, mitoxantrone hydrochloride 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 CRi, partial remission, or persistent disease may receive a second course of induction chemotherapy. Patients achieving CR or CRp may continue on to Consolidation Chemotherapy. CONSOLIDATION CHEMOTHERAPY (G-CLA): Beginning within 6 weeks of achieving CR/CRp/CRi, patients receive G-CLA comprising filgrastim SC on days 0-5, cladribine IV over 2 hours daily on days 1-5, and cytarabine IV over 2 hours daily on days 1-5. Treatment continues for up to 4 courses in the absence of disease progression or unacceptable toxicity. Cladribine: Given IV Cytarabine: Given IV Filgrastim: Given SC Laboratory Biomarker Analysis: Correlative studies Mitoxantrone Hydrochloride: Given IV	6	10	10	10	10
EG005	Relapsed/Refractory Group Mitoxantrone Hydrochloride 14 mg/m^2	INDUCTION CHEMOTHERAPY (G-CLAM): Patients receive G-CLAM chemotherapy comprising filgrastim SC daily on days 0-5, mitoxantrone hydrochloride 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 CRi, partial remission, or persistent disease may receive a second course of induction chemotherapy. Patients achieving CR or CRp may continue on to Consolidation Chemotherapy. CONSOLIDATION CHEMOTHERAPY (G-CLA): Beginning within 6 weeks of achieving CR/CRp/CRi, patients receive G-CLA comprising filgrastim SC on days 0-5, cladribine IV over 2 hours daily on days 1-5, and cytarabine IV over 2 hours daily on days 1-5. Treatment continues for up to 4 courses in the absence of disease progression or unacceptable toxicity. Cladribine: Given IV Cytarabine: Given IV Filgrastim: Given SC Laboratory Biomarker Analysis: Correlative studies Mitoxantrone Hydrochloride: Given IV	4	6	6	6	6
EG006	Relapsed/Refractory Group Mitoxantrone Hydrochloride 16 mg/m^2	INDUCTION CHEMOTHERAPY (G-CLAM): Patients receive G-CLAM chemotherapy comprising filgrastim SC daily on days 0-5, mitoxantrone hydrochloride 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 CRi, partial remission, or persistent disease may receive a second course of induction chemotherapy. Patients achieving CR or CRp may continue on to Consolidation Chemotherapy. CONSOLIDATION CHEMOTHERAPY (G-CLA): Beginning within 6 weeks of achieving CR/CRp/CRi, patients receive G-CLA comprising filgrastim SC on days 0-5, cladribine IV over 2 hours daily on days 1-5, and cytarabine IV over 2 hours daily on days 1-5. Treatment continues for up to 4 courses in the absence of disease progression or unacceptable toxicity. Cladribine: Given IV Cytarabine: Given IV Filgrastim: Given SC Laboratory Biomarker Analysis: Correlative studies Mitoxantrone Hydrochloride: Given IV	4	6	6	6	6
EG007	Relapsed/Refractory Group Mitoxantrone Hydrochloride 18 mg/m^2	INDUCTION CHEMOTHERAPY (G-CLAM): Patients receive G-CLAM chemotherapy comprising filgrastim SC daily on days 0-5, mitoxantrone hydrochloride 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 CRi, partial remission, or persistent disease may receive a second course of induction chemotherapy. Patients achieving CR or CRp may continue on to Consolidation Chemotherapy. CONSOLIDATION CHEMOTHERAPY (G-CLA): Beginning within 6 weeks of achieving CR/CRp/CRi, patients receive G-CLA comprising filgrastim SC on days 0-5, cladribine IV over 2 hours daily on days 1-5, and cytarabine IV over 2 hours daily on days 1-5. Treatment continues for up to 4 courses in the absence of disease progression or unacceptable toxicity. Cladribine: Given IV Cytarabine: Given IV Filgrastim: Given SC Laboratory Biomarker Analysis: Correlative studies Mitoxantrone Hydrochloride: Given IV	2	4	4	4	4
EG008	Phase 2 Newly Diagnosed Group 18 mg/m^2	INDUCTION CHEMOTHERAPY (G-CLAM): Patients receive G-CLAM chemotherapy comprising filgrastim SC daily on days 0-5, mitoxantrone hydrochloride 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 CRi, partial remission, or persistent disease may receive a second course of induction chemotherapy. Patients achieving CR or CRp may continue on to Consolidation Chemotherapy. CONSOLIDATION CHEMOTHERAPY (G-CLA): Beginning within 6 weeks of achieving CR/CRp/CRi, patients receive G-CLA comprising filgrastim SC on days 0-5, cladribine IV over 2 hours daily on days 1-5, and cytarabine IV over 2 hours daily on days 1-5. Treatment continues for up to 4 courses in the absence of disease progression or unacceptable toxicity. Cladribine: Given IV Cytarabine: Given IV Filgrastim: Given SC Laboratory Biomarker Analysis: Correlative studies Mitoxantrone Hydrochloride: Given IV	40	106	106	100	106
EG009	Phase 2 Relapsed/Refractory Group 16 mg/m^2	INDUCTION CHEMOTHERAPY (G-CLAM): Patients receive G-CLAM chemotherapy comprising filgrastim SC daily on days 0-5, mitoxantrone hydrochloride 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 CRi, partial remission, or persistent disease may receive a second course of induction chemotherapy. Patients achieving CR or CRp may continue on to Consolidation Chemotherapy. CONSOLIDATION CHEMOTHERAPY (G-CLA): Beginning within 6 weeks of achieving CR/CRp/CRi, patients receive G-CLA comprising filgrastim SC on days 0-5, cladribine IV over 2 hours daily on days 1-5, and cytarabine IV over 2 hours daily on days 1-5. Treatment continues for up to 4 courses in the absence of disease progression or unacceptable toxicity. Cladribine: Given IV Cytarabine: Given IV Filgrastim: Given SC Laboratory Biomarker Analysis: Correlative studies Mitoxantrone Hydrochloride: Given IV	21	34	34	31	34

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Febrile Neutropenia	Infections and infestations	Systematic Assessment	EG0007 affected9 at risk EG0017 affected9 at risk EG0027 affected9 at risk EG0035 affected6 at risk EG0047 affected10 at risk EG0056 affected6 at risk EG0066 affected6 at risk EG0074 affected4 at risk EG00890 affected106 at risk EG00931 affected34 at risk
Fever	Infections and infestations	Systematic Assessment	EG0004 affected9 at risk EG0011 affected9 at risk EG0020 affected9 at risk EG003
Tumor Lysis Syndrome	Infections and infestations	Systematic Assessment	EG0000 affected9 at risk EG0010 affected9 at risk EG0022 affected9 at risk EG003
Maculopapular Rash	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0002 affected9 at risk EG0012 affected9 at risk EG0026 affected9 at risk EG003
Bacteremia	Infections and infestations	Systematic Assessment	EG0004 affected9 at risk EG0015 affected9 at risk EG0025 affected9 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0002 affected9 at risk EG0011 affected9 at risk EG0022 affected9 at risk EG003
Fungal Pneumonia	Infections and infestations	Systematic Assessment	EG0001 affected9 at risk EG0010 affected9 at risk EG0021 affected9 at risk EG003
Pneumonia	Infections and infestations	Systematic Assessment	EG0003 affected9 at risk EG0010 affected9 at risk EG0020 affected9 at risk EG003
Cytokin Storm	Immune system disorders	Systematic Assessment	EG0000 affected9 at risk EG0010 affected9 at risk EG0021 affected9 at risk EG003
Anaphylaxis	Immune system disorders	Systematic Assessment	EG0000 affected9 at risk EG0011 affected9 at risk EG0020 affected9 at risk EG003
Papulopustular Rash	Infections and infestations	Systematic Assessment	EG0001 affected9 at risk EG0010 affected9 at risk EG0021 affected9 at risk EG003
Bone Pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 affected9 at risk EG0011 affected9 at risk EG0020 affected9 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 affected9 at risk EG0010 affected9 at risk EG0020 affected9 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 affected9 at risk EG0010 affected9 at risk EG0020 affected9 at risk EG003
Sepsis	Infections and infestations	Systematic Assessment	EG0000 affected9 at risk EG0011 affected9 at risk EG0021 affected9 at risk EG003
Soft Tissue Infection	Infections and infestations	Systematic Assessment	EG0000 affected9 at risk EG0010 affected9 at risk EG0021 affected9 at risk EG003
Catheter Related Infection	Infections and infestations	Systematic Assessment	EG0000 affected9 at risk EG0010 affected9 at risk EG0020 affected9 at risk EG003
Aspiration	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected9 at risk EG0011 affected9 at risk EG0020 affected9 at risk EG003
Urinary Tract Infection	Infections and infestations	Systematic Assessment	EG0000 affected9 at risk EG0010 affected9 at risk EG0020 affected9 at risk EG003
Sinusitis	Infections and infestations	Systematic Assessment	EG0002 affected9 at risk EG0010 affected9 at risk EG0020 affected9 at risk EG003
Skin Infection	Infections and infestations	Systematic Assessment	EG0000 affected9 at risk EG0010 affected9 at risk EG0020 affected9 at risk EG003
Respiratory Failure	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected9 at risk EG0011 affected9 at risk EG0022 affected9 at risk EG003
Pulmonary Edema	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected9 at risk EG0010 affected9 at risk EG0020 affected9 at risk EG003
Upper Respiratory Infection	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected9 at risk EG0010 affected9 at risk EG0020 affected9 at risk EG003
Bronchopulmonary hemorrhage	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected9 at risk EG0010 affected9 at risk EG0021 affected9 at risk EG003
Nausea	Gastrointestinal disorders	Systematic Assessment	EG0001 affected9 at risk EG0011 affected9 at risk EG0020 affected9 at risk EG003
Diarrhea	Gastrointestinal disorders	Systematic Assessment	EG0002 affected9 at risk EG0011 affected9 at risk EG0020 affected9 at risk EG003
Esophagitis	Gastrointestinal disorders	Systematic Assessment	EG0000 affected9 at risk EG0010 affected9 at risk EG0020 affected9 at risk EG003
Dysphagia	Gastrointestinal disorders	Systematic Assessment	EG0000 affected9 at risk EG0010 affected9 at risk EG0020 affected9 at risk EG003
Chloecystitis	Hepatobiliary disorders	Systematic Assessment	EG0000 affected9 at risk EG0010 affected9 at risk EG0020 affected9 at risk EG003
Enterocolitis infectious	Infections and infestations	Systematic Assessment	EG0000 affected9 at risk EG0010 affected9 at risk EG0020 affected9 at risk EG003
Paroxysmal atrial tachycardia	Cardiac disorders	Systematic Assessment	EG0001 affected9 at risk EG0011 affected9 at risk EG0020 affected9 at risk EG003
Hypotension	Vascular disorders	Systematic Assessment	EG0001 affected9 at risk EG0011 affected9 at risk EG0020 affected9 at risk EG003
Restrictive cardiomyopathy	Cardiac disorders	Systematic Assessment	EG0000 affected9 at risk EG0010 affected9 at risk EG0020 affected9 at risk EG003
Fall	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 affected9 at risk EG0010 affected9 at risk EG0020 affected9 at risk EG003
Intracranial hemorrhage	Nervous system disorders	Systematic Assessment	EG0001 affected9 at risk EG0011 affected9 at risk EG0020 affected9 at risk EG003
Encephalopathy	Nervous system disorders	Systematic Assessment	EG0000 affected9 at risk EG0010 affected9 at risk EG0020 affected9 at risk EG003
Delirium	Psychiatric disorders	Systematic Assessment	EG0001 affected9 at risk EG0010 affected9 at risk EG0020 affected9 at risk EG003
Seizure	Nervous system disorders	Systematic Assessment	EG0000 affected9 at risk EG0010 affected9 at risk EG0020 affected9 at risk EG003
Headache	Nervous system disorders	Systematic Assessment	EG0000 affected9 at risk EG0010 affected9 at risk EG0020 affected9 at risk EG003
Unequal limb length	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 affected9 at risk EG0010 affected9 at risk EG0020 affected9 at risk EG003
Insomnia	Psychiatric disorders	Systematic Assessment	EG0000 affected9 at risk EG0010 affected9 at risk EG0021 affected9 at risk EG003
Acute kidney injury	Renal and urinary disorders	Systematic Assessment	EG0000 affected9 at risk EG0010 affected9 at risk EG0022 affected9 at risk EG003
Hepatic failure	Hepatobiliary disorders	Systematic Assessment	EG0002 affected9 at risk EG0010 affected9 at risk EG0021 affected9 at risk EG003
Hyponatremia	Metabolism and nutrition disorders	Systematic Assessment	EG0001 affected9 at risk EG0011 affected9 at risk EG0020 affected9 at risk EG003
Hypokalemia	Metabolism and nutrition disorders	Systematic Assessment	EG0001 affected9 at risk EG0010 affected9 at risk EG0020 affected9 at risk EG003
Vitreous hemorrhage	Eye disorders	Systematic Assessment	EG0000 affected9 at risk EG0010 affected9 at risk EG0020 affected9 at risk EG003
Anorexia	Metabolism and nutrition disorders	Systematic Assessment	EG0001 affected9 at risk EG0010 affected9 at risk EG0020 affected9 at risk EG003
Multi-organ failure	General disorders	Systematic Assessment	EG0000 affected9 at risk EG0010 affected9 at risk EG0021 affected9 at risk EG003
Uveitis	Eye disorders	Systematic Assessment	EG0001 affected9 at risk EG0010 affected9 at risk EG0020 affected9 at risk EG003
Hearing impaired	Ear and labyrinth disorders	Systematic Assessment	EG0000 affected9 at risk EG0011 affected9 at risk EG0020 affected9 at risk EG003
Otitis media	Infections and infestations	Systematic Assessment	EG0000 affected9 at risk EG0011 affected9 at risk EG0020 affected9 at risk EG003

ID	Term
D015456	Leukemia, Biphenotypic, Acute
D015470	Leukemia, Myeloid, Acute

ID	Term
D007945	Leukemia, Lymphoid
D007938	Leukemia
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases
D007951	Leukemia, Myeloid

ID	Term
D015762	2-Chloroadenosine
D000241	Adenosine
D011684	Purine Nucleosides
D011687	Purines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D003839	Deoxyadenosines
D003853	Deoxyribonucleosides
D009705	Nucleosides
D009706	Nucleic Acids, Nucleotides, and Nucleosides
D012263	Ribonucleosides
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D001087	Arabinonucleosides
D003115	Colony-Stimulating Factors
D006023	Glycoproteins
D006001	Glycoconjugates
D002241	Carbohydrates
D016298	Hematopoietic Cell Growth Factors
D016207	Cytokines
D036341	Intercellular Signaling Peptides and Proteins
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins
D011506	Proteins
D001685	Biological Factors
D000880	Anthraquinones
D000095322	Anthrones
D000873	Anthracenes
D011084	Polycyclic Aromatic Hydrocarbons
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D011809	Quinones
D011083	Polycyclic Compounds

ID	Term
D017338	Cladribine
D003561	Cytarabine
D000069585	Filgrastim
D016179	Granulocyte Colony-Stimulating Factor
D008942	Mitoxantrone