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

• Sponsor: Fred Hutchinson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT02044796
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 199
• Location: 1
• Arm: 1
• Actual Duration (Months): 50.7
• Patients Per Site Per Month: 3.9

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Biphenotypic Leukemia; de Novo Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia	Drug: Cladribine; Drug: Cytarabine; Biological: Filgrastim; Other: Laboratory Biomarker Analysis; Drug: Mitoxantrone Hydrochloride	Phase 1/Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. 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:

1. 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.

2. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 199 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Myelodysplastic Syndromes (MDS)
• Actual Study Start Date: Jan 23, 2014
• Actual Primary Completion Date: Mar 9, 2018
• Actual Study Completion Date: Apr 16, 2018

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (filgrastim, mitoxantrone, cladribine, cytarabine) 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; Given IV; Other Names: 2-CdA 2CDA CdA Cladribina Leustat Leustatin Leustatine RWJ-26251 ; Drug: Cytarabine; Given IV; Other Names: .beta.-Cytosine arabinoside 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone 1-.beta.-D-Arabinofuranosylcytosine 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone 1-Beta-D-arabinofuranosylcytosine 1.beta.-D-Arabinofuranosylcytosine 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl- 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl- Alexan Ara-C ARA-cell Arabine Arabinofuranosylcytosine Arabinosylcytosine Aracytidine Aracytin Aracytine Beta-Cytosine Arabinoside CHX-3311 Cytarabinum Cytarbel Cytosar Cytosar-U Cytosine Arabinoside Cytosine-.beta.-arabinoside Cytosine-beta-arabinoside Erpalfa Starasid Tarabine PFS U 19920 U-19920 Udicil WR-28453 ; Biological: Filgrastim; Given SC; Other Names: Filgrastim XM02 Filgrastim-sndz G-CSF Neupogen r-metHuG-CSF Recombinant Methionyl Human Granulocyte Colony Stimulating Factor rG-CSF Tbo-filgrastim Tevagrastim Zarxio ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Mitoxantrone Hydrochloride; Given IV; Other Names: CL 232315 DHAD DHAQ Dihydroxyanthracenedione Dihydrochloride Mitoxantrone Dihydrochloride Mitoxantroni Hydrochloridum Mitozantrone Hydrochloride Mitroxone Neotalem Novantrone Onkotrone Pralifan

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Dose Limiting Toxicities of Mitoxantrone (Phase I, Dose Level 4) [Up to day 45 after start of induction chemotherapy]

   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

2. Minimal Residual Disease Negative Complete Remission Rate in Patients With Newly Diagnosed Disease (Phase II) [Up to day 45 after start of second course of induction chemotherapy]

   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).

Secondary Outcome Measures

1. Overall Survival (Phase II) [From date of randomization until the date of death from any cause, assessed up to 12 months]

   Number of subjects that have survived

2. Remission Rate (Complete Remission and Complete Remission With Incomplete Platelet Count Recovery) of This Regimen in Patients With Relapsed/Refractory Disease (Phase II) [Up to 5 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington	United States	98109

Sponsors and Collaborators

• Fred Hutchinson Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Roland Walter, Fred Hutch/University of Washington Cancer Consortium

Study Documents (Full-Text)

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form - Apr 17, 2017

More Information

Publications

None provided.

• Responsible Party: Fred Hutchinson Cancer Center
• ClinicalTrials.gov Identifier: NCT02044796
• Other Study ID Numbers: 2734.00; NCI-2013-02465; 2734.00; P30CA015704
• First Posted: Jan 24, 2014
• Last Update Posted: Jan 10, 2020
• Last Verified: Dec 1, 2019

• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Leukemia, Biphenotypic, Acute; Myelodysplastic Syndromes; Syndrome; Cytarabine; 2-chloro-3'-deoxyadenosine; Mitoxantrone; Cladribine; Lenograstim

Study Results

Participant Flow

Arm/Group Title	Newly Diagnosed Group Mitoxantrone Hydrochloride 12 mg/m^2	Newly Diagnosed Group Mitoxantrone Hydrochloride 14 mg/m^2	Newly Diagnosed Group Mitoxantrone Hydrochloride 16 mg/m^2	Newly Diagnosed Group Mitoxantrone Hydrochloride 18mg/m^2	Relapsed/Refractory Group Mitoxantrone Hydrochloride 12 mg/m^2	Relapsed/Refractory Group Mitoxantrone Hydrochloride 14 mg/m^2	Relapsed/Refractory Group Mitoxantrone Hydrochloride 16 mg/m^2	Relapsed/Refractory Group Mitoxantrone Hydrochloride 18 mg/m^2	Phase 2 Newly Diagnosed Group 18 mg/m^2	Phase 2 Relapsed/Refractory Group 16 mg/m^2
Arm/Group Description	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	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	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	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	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	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	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	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	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	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
Period Title: Overall Study
STARTED	9	9	9	6	10	6	6	4	106	34
COMPLETED	9	9	9	6	10	6	6	4	106	34
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Newly Diagnosed	Relapsed/Refractory Group	Total
Arm/Group Description	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	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	Total of all reporting groups
Overall Participants	139	60	199
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	58.1	58.2	58.1
Sex: Female, Male (Count of Participants)
Female	59 42.4%	25 41.7%	84 42.2%
Male	80 57.6%	35 58.3%	115 57.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 1.4%	0 0%	2 1%
Asian	7 5%	3 5%	10 5%
Native Hawaiian or Other Pacific Islander	3 2.2%	0 0%	3 1.5%
Black or African American	6 4.3%	1 1.7%	7 3.5%
White	112 80.6%	52 86.7%	164 82.4%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	9 6.5%	4 6.7%	13 6.5%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Dose Limiting Toxicities of Mitoxantrone (Phase I, Dose Level 4)
Description	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
Time Frame	Up to day 45 after start of induction chemotherapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Newly Diagnosed Group	Relapsed/Refractory Group
Arm/Group Description	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	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
Measure Participants	6	4
Count of Participants [Participants]	1 0.7%	2 3.3%

2. Primary Outcome

Title	Minimal Residual Disease Negative Complete Remission Rate in Patients With Newly Diagnosed Disease (Phase II)
Description	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).
Time Frame	Up to day 45 after start of second course of induction chemotherapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Newly Diagnosed Group	Relapsed/Refractory
Arm/Group Description	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	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
Measure Participants	112	40
Count of Participants [Participants]	95 68.3%	22 36.7%

3. Secondary Outcome

Title	Overall Survival (Phase II)
Description	Number of subjects that have survived
Time Frame	From date of randomization until the date of death from any cause, assessed up to 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase 2 Newly Diagnosed Group 18 mg/m^2	Phase 2 Relapsed/Refractory Group 16 mg/m^2
Arm/Group Description	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	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
Measure Participants	106	34
Number [Participants]	66 47.5%	13 21.7%

4. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Phase 2 Relapsed/Refractory Group 16 mg/m^2
Arm/Group Description	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
Measure Participants	40
Count of Participants [Participants]	24 17.3%

Adverse Events

Time Frame	All-Cause Mortality assessed for up to 12 months; Serious and Other Adverse Events assessed for up to 1 month after treatment concluded
Arm/Group Title	Newly Diagnosed Group Mitoxantrone Hydrochloride 12 mg/m^2		Newly Diagnosed Group Mitoxantrone Hydrochloride 14 mg/m^2		Newly Diagnosed Group Mitoxantrone Hydrochloride 16 mg/m^2		Newly Diagnosed Group Mitoxantrone Hydrochloride 18 mg/m^2		Relapsed/Refractory Group Mitoxantrone Hydrochloride 12 mg/m^2		Relapsed/Refractory Group Mitoxantrone Hydrochloride 14 mg/m^2		Relapsed/Refractory Group Mitoxantrone Hydrochloride 16 mg/m^2		Relapsed/Refractory Group Mitoxantrone Hydrochloride 18 mg/m^2		Phase 2 Newly Diagnosed Group 18 mg/m^2		Phase 2 Relapsed/Refractory Group 16 mg/m^2
Arm/Group Description	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		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		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		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		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		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		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		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		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		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
All Cause Mortality
	Newly Diagnosed Group Mitoxantrone Hydrochloride 12 mg/m^2		Newly Diagnosed Group Mitoxantrone Hydrochloride 14 mg/m^2		Newly Diagnosed Group Mitoxantrone Hydrochloride 16 mg/m^2		Newly Diagnosed Group Mitoxantrone Hydrochloride 18 mg/m^2		Relapsed/Refractory Group Mitoxantrone Hydrochloride 12 mg/m^2		Relapsed/Refractory Group Mitoxantrone Hydrochloride 14 mg/m^2		Relapsed/Refractory Group Mitoxantrone Hydrochloride 16 mg/m^2		Relapsed/Refractory Group Mitoxantrone Hydrochloride 18 mg/m^2		Phase 2 Newly Diagnosed Group 18 mg/m^2		Phase 2 Relapsed/Refractory Group 16 mg/m^2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		2/9 (22.2%)		2/9 (22.2%)		1/6 (16.7%)		6/10 (60%)		4/6 (66.7%)		4/6 (66.7%)		2/4 (50%)		40/106 (37.7%)		21/34 (61.8%)
Serious Adverse Events
	Newly Diagnosed Group Mitoxantrone Hydrochloride 12 mg/m^2		Newly Diagnosed Group Mitoxantrone Hydrochloride 14 mg/m^2		Newly Diagnosed Group Mitoxantrone Hydrochloride 16 mg/m^2		Newly Diagnosed Group Mitoxantrone Hydrochloride 18 mg/m^2		Relapsed/Refractory Group Mitoxantrone Hydrochloride 12 mg/m^2		Relapsed/Refractory Group Mitoxantrone Hydrochloride 14 mg/m^2		Relapsed/Refractory Group Mitoxantrone Hydrochloride 16 mg/m^2		Relapsed/Refractory Group Mitoxantrone Hydrochloride 18 mg/m^2		Phase 2 Newly Diagnosed Group 18 mg/m^2		Phase 2 Relapsed/Refractory Group 16 mg/m^2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/9 (0%)		0/9 (0%)		0/6 (0%)		0/10 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		0/106 (0%)		0/34 (0%)
Other (Not Including Serious) Adverse Events
	Newly Diagnosed Group Mitoxantrone Hydrochloride 12 mg/m^2		Newly Diagnosed Group Mitoxantrone Hydrochloride 14 mg/m^2		Newly Diagnosed Group Mitoxantrone Hydrochloride 16 mg/m^2		Newly Diagnosed Group Mitoxantrone Hydrochloride 18 mg/m^2		Relapsed/Refractory Group Mitoxantrone Hydrochloride 12 mg/m^2		Relapsed/Refractory Group Mitoxantrone Hydrochloride 14 mg/m^2		Relapsed/Refractory Group Mitoxantrone Hydrochloride 16 mg/m^2		Relapsed/Refractory Group Mitoxantrone Hydrochloride 18 mg/m^2		Phase 2 Newly Diagnosed Group 18 mg/m^2		Phase 2 Relapsed/Refractory Group 16 mg/m^2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/9 (88.9%)		8/9 (88.9%)		9/9 (100%)		6/6 (100%)		10/10 (100%)		6/6 (100%)		6/6 (100%)		4/4 (100%)		100/106 (94.3%)		31/34 (91.2%)
Cardiac disorders
Paroxysmal atrial tachycardia	1/9 (11.1%)		1/9 (11.1%)		0/9 (0%)		0/6 (0%)		1/10 (10%)		1/6 (16.7%)		0/6 (0%)		1/4 (25%)		11/106 (10.4%)		0/34 (0%)
Restrictive cardiomyopathy	0/9 (0%)		0/9 (0%)		0/9 (0%)		1/6 (16.7%)		1/10 (10%)		0/6 (0%)		0/6 (0%)		1/4 (25%)		6/106 (5.7%)		0/34 (0%)
Ear and labyrinth disorders
Hearing impaired	0/9 (0%)		1/9 (11.1%)		0/9 (0%)		0/6 (0%)		0/10 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		0/106 (0%)		0/34 (0%)
Eye disorders
Vitreous hemorrhage	0/9 (0%)		0/9 (0%)		0/9 (0%)		0/6 (0%)		1/10 (10%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		1/106 (0.9%)		0/34 (0%)
Uveitis	1/9 (11.1%)		0/9 (0%)		0/9 (0%)		0/6 (0%)		0/10 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		0/106 (0%)		0/34 (0%)
Gastrointestinal disorders
Nausea	1/9 (11.1%)		1/9 (11.1%)		0/9 (0%)		0/6 (0%)		2/10 (20%)		1/6 (16.7%)		2/6 (33.3%)		1/4 (25%)		6/106 (5.7%)		0/34 (0%)
Diarrhea	2/9 (22.2%)		1/9 (11.1%)		0/9 (0%)		0/6 (0%)		0/10 (0%)		0/6 (0%)		0/6 (0%)		1/4 (25%)		5/106 (4.7%)		2/34 (5.9%)
Esophagitis	0/9 (0%)		0/9 (0%)		0/9 (0%)		1/6 (16.7%)		0/10 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		2/106 (1.9%)		2/34 (5.9%)
Dysphagia	0/9 (0%)		0/9 (0%)		0/9 (0%)		1/6 (16.7%)		1/10 (10%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		0/106 (0%)		0/34 (0%)
General disorders
Multi-organ failure	0/9 (0%)		0/9 (0%)		1/9 (11.1%)		1/6 (16.7%)		0/10 (0%)		0/6 (0%)		0/6 (0%)		1/4 (25%)		3/106 (2.8%)		0/34 (0%)
Hepatobiliary disorders
Chloecystitis	0/9 (0%)		0/9 (0%)		0/9 (0%)		0/6 (0%)		1/10 (10%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		1/106 (0.9%)		0/34 (0%)
Hepatic failure	2/9 (22.2%)		0/9 (0%)		1/9 (11.1%)		1/6 (16.7%)		0/10 (0%)		1/6 (16.7%)		1/6 (16.7%)		1/4 (25%)		9/106 (8.5%)		1/34 (2.9%)
Immune system disorders
Cytokin Storm	0/9 (0%)		0/9 (0%)		1/9 (11.1%)		0/6 (0%)		0/10 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		0/106 (0%)		0/34 (0%)
Anaphylaxis	0/9 (0%)		1/9 (11.1%)		0/9 (0%)		0/6 (0%)		0/10 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		1/106 (0.9%)		0/34 (0%)
Infections and infestations
Febrile Neutropenia	7/9 (77.8%)		7/9 (77.8%)		7/9 (77.8%)		5/6 (83.3%)		7/10 (70%)		6/6 (100%)		6/6 (100%)		4/4 (100%)		90/106 (84.9%)		31/34 (91.2%)
Fever	4/9 (44.4%)		1/9 (11.1%)		0/9 (0%)		2/6 (33.3%)		1/10 (10%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		6/106 (5.7%)		1/34 (2.9%)
Tumor Lysis Syndrome	0/9 (0%)		0/9 (0%)		2/9 (22.2%)		0/6 (0%)		1/10 (10%)		0/6 (0%)		1/6 (16.7%)		1/4 (25%)		7/106 (6.6%)		3/34 (8.8%)
Bacteremia	4/9 (44.4%)		5/9 (55.6%)		5/9 (55.6%)		2/6 (33.3%)		7/10 (70%)		3/6 (50%)		5/6 (83.3%)		2/4 (50%)		41/106 (38.7%)		15/34 (44.1%)
Fungal Pneumonia	1/9 (11.1%)		0/9 (0%)		1/9 (11.1%)		1/6 (16.7%)		0/10 (0%)		1/6 (16.7%)		0/6 (0%)		1/4 (25%)		22/106 (20.8%)		5/34 (14.7%)
Pneumonia	3/9 (33.3%)		0/9 (0%)		0/9 (0%)		1/6 (16.7%)		1/10 (10%)		0/6 (0%)		1/6 (16.7%)		0/4 (0%)		20/106 (18.9%)		1/34 (2.9%)
Papulopustular Rash	1/9 (11.1%)		0/9 (0%)		1/9 (11.1%)		0/6 (0%)		0/10 (0%)		0/6 (0%)		1/6 (16.7%)		0/4 (0%)		1/106 (0.9%)		0/34 (0%)
Sepsis	0/9 (0%)		1/9 (11.1%)		1/9 (11.1%)		1/6 (16.7%)		1/10 (10%)		0/6 (0%)		1/6 (16.7%)		1/4 (25%)		10/106 (9.4%)		3/34 (8.8%)
Soft Tissue Infection	0/9 (0%)		0/9 (0%)		1/9 (11.1%)		2/6 (33.3%)		1/10 (10%)		1/6 (16.7%)		2/6 (33.3%)		1/4 (25%)		12/106 (11.3%)		4/34 (11.8%)
Catheter Related Infection	0/9 (0%)		0/9 (0%)		0/9 (0%)		1/6 (16.7%)		0/10 (0%)		0/6 (0%)		1/6 (16.7%)		0/4 (0%)		2/106 (1.9%)		1/34 (2.9%)
Urinary Tract Infection	0/9 (0%)		0/9 (0%)		0/9 (0%)		0/6 (0%)		1/10 (10%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		3/106 (2.8%)		0/34 (0%)
Sinusitis	2/9 (22.2%)		0/9 (0%)		0/9 (0%)		0/6 (0%)		1/10 (10%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		1/106 (0.9%)		0/34 (0%)
Skin Infection	0/9 (0%)		0/9 (0%)		0/9 (0%)		0/6 (0%)		1/10 (10%)		0/6 (0%)		1/6 (16.7%)		0/4 (0%)		1/106 (0.9%)		0/34 (0%)
Enterocolitis infectious	0/9 (0%)		0/9 (0%)		0/9 (0%)		0/6 (0%)		0/10 (0%)		1/6 (16.7%)		0/6 (0%)		0/4 (0%)		4/106 (3.8%)		2/34 (5.9%)
Otitis media	0/9 (0%)		1/9 (11.1%)		0/9 (0%)		0/6 (0%)		0/10 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		0/106 (0%)		0/34 (0%)
Injury, poisoning and procedural complications
Fall	1/9 (11.1%)		0/9 (0%)		0/9 (0%)		0/6 (0%)		0/10 (0%)		0/6 (0%)		0/6 (0%)		1/4 (25%)		2/106 (1.9%)		1/34 (2.9%)
Metabolism and nutrition disorders
Hyponatremia	1/9 (11.1%)		1/9 (11.1%)		0/9 (0%)		0/6 (0%)		0/10 (0%)		0/6 (0%)		0/6 (0%)		1/4 (25%)		8/106 (7.5%)		3/34 (8.8%)
Hypokalemia	1/9 (11.1%)		0/9 (0%)		0/9 (0%)		0/6 (0%)		0/10 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		7/106 (6.6%)		2/34 (5.9%)
Anorexia	1/9 (11.1%)		0/9 (0%)		0/9 (0%)		0/6 (0%)		0/10 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		1/106 (0.9%)		0/34 (0%)
Musculoskeletal and connective tissue disorders
Bone Pain	0/9 (0%)		1/9 (11.1%)		0/9 (0%)		1/6 (16.7%)		2/10 (20%)		1/6 (16.7%)		0/6 (0%)		0/4 (0%)		3/106 (2.8%)		0/34 (0%)
Arthralgia	0/9 (0%)		0/9 (0%)		0/9 (0%)		1/6 (16.7%)		1/10 (10%)		0/6 (0%)		0/6 (0%)		1/4 (25%)		0/106 (0%)		0/34 (0%)
Myalgia	0/9 (0%)		0/9 (0%)		0/9 (0%)		0/6 (0%)		0/10 (0%)		0/6 (0%)		0/6 (0%)		1/4 (25%)		0/106 (0%)		0/34 (0%)
Unequal limb length	0/9 (0%)		0/9 (0%)		0/9 (0%)		0/6 (0%)		0/10 (0%)		1/6 (16.7%)		0/6 (0%)		1/4 (25%)		0/106 (0%)		0/34 (0%)
Nervous system disorders
Intracranial hemorrhage	1/9 (11.1%)		1/9 (11.1%)		0/9 (0%)		0/6 (0%)		0/10 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		1/106 (0.9%)		0/34 (0%)
Encephalopathy	0/9 (0%)		0/9 (0%)		0/9 (0%)		0/6 (0%)		0/10 (0%)		0/6 (0%)		0/6 (0%)		1/4 (25%)		1/106 (0.9%)		0/34 (0%)
Seizure	0/9 (0%)		0/9 (0%)		0/9 (0%)		0/6 (0%)		0/10 (0%)		0/6 (0%)		1/6 (16.7%)		0/4 (0%)		0/106 (0%)		0/34 (0%)
Headache	0/9 (0%)		0/9 (0%)		0/9 (0%)		1/6 (16.7%)		0/10 (0%)		0/6 (0%)		1/6 (16.7%)		1/4 (25%)		1/106 (0.9%)		0/34 (0%)
Psychiatric disorders
Delirium	1/9 (11.1%)		0/9 (0%)		0/9 (0%)		0/6 (0%)		1/10 (10%)		1/6 (16.7%)		0/6 (0%)		0/4 (0%)		2/106 (1.9%)		0/34 (0%)
Insomnia	0/9 (0%)		0/9 (0%)		1/9 (11.1%)		1/6 (16.7%)		0/10 (0%)		0/6 (0%)		0/6 (0%)		1/4 (25%)		1/106 (0.9%)		0/34 (0%)
Renal and urinary disorders
Acute kidney injury	0/9 (0%)		0/9 (0%)		2/9 (22.2%)		1/6 (16.7%)		0/10 (0%)		0/6 (0%)		0/6 (0%)		1/4 (25%)		7/106 (6.6%)		2/34 (5.9%)
Respiratory, thoracic and mediastinal disorders
Hypoxia	2/9 (22.2%)		1/9 (11.1%)		2/9 (22.2%)		2/6 (33.3%)		3/10 (30%)		0/6 (0%)		0/6 (0%)		3/4 (75%)		27/106 (25.5%)		6/34 (17.6%)
Aspiration	0/9 (0%)		1/9 (11.1%)		0/9 (0%)		0/6 (0%)		1/10 (10%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		3/106 (2.8%)		0/34 (0%)
Respiratory Failure	0/9 (0%)		1/9 (11.1%)		2/9 (22.2%)		1/6 (16.7%)		0/10 (0%)		1/6 (16.7%)		0/6 (0%)		1/4 (25%)		5/106 (4.7%)		1/34 (2.9%)
Pulmonary Edema	1/9 (11.1%)		0/9 (0%)		0/9 (0%)		1/6 (16.7%)		0/10 (0%)		0/6 (0%)		1/6 (16.7%)		3/4 (75%)		8/106 (7.5%)		0/34 (0%)
Upper Respiratory Infection	0/9 (0%)		0/9 (0%)		0/9 (0%)		1/6 (16.7%)		0/10 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		1/106 (0.9%)		1/34 (2.9%)
Bronchopulmonary hemorrhage	0/9 (0%)		0/9 (0%)		1/9 (11.1%)		0/6 (0%)		0/10 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		1/106 (0.9%)		0/34 (0%)
Skin and subcutaneous tissue disorders
Maculopapular Rash	2/9 (22.2%)		2/9 (22.2%)		6/9 (66.7%)		1/6 (16.7%)		2/10 (20%)		2/6 (33.3%)		0/6 (0%)		1/4 (25%)		27/106 (25.5%)		3/34 (8.8%)
Vascular disorders
Hypotension	1/9 (11.1%)		1/9 (11.1%)		0/9 (0%)		0/6 (0%)		0/10 (0%)		1/6 (16.7%)		1/6 (16.7%)		0/4 (0%)		6/106 (5.7%)		3/34 (8.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.