Decitabine With GCLAM for Adults With Newly Diagnosed, Relapsed, or Refractory AML or High-Risk MDS

• Sponsor: Fred Hutchinson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT02921061
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 28
• Location: 1
• Arm: 1
• Actual Duration (Months): 23.2
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

This phase I/II trial studies the side effects and best dose of decitabine when given together with filgrastim, cladribine, cytarabine, and mitoxantrone hydrochloride in treating patients with acute myeloid leukemia or myelodysplastic syndrome that is newly diagnosed, has come back or has not responded to treatment. Drugs used in chemotherapy, such as decitabine, cladribine, cytarabine, and mitoxantrone hydrochloride work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Colony-stimulating factors, such as filgrastim, may increase the production of blood cells and may help the immune system recover from the side effects of chemotherapy. Decitabine, filgrastim, cladribine, cytarabine, and mitoxantrone hydrochloride may work better in treating patients with acute myeloid leukemia and myelodysplastic syndrome.

Condition or Disease	Intervention/Treatment	Phase
Mixed Phenotype Acute Leukemia; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Recurrent High Risk Myelodysplastic Syndrome; Refractory Acute Myeloid Leukemia; Refractory High Risk Myelodysplastic Syndrome; Untreated Adult Acute Myeloid Leukemia	Drug: Cladribine; Drug: Cytarabine; Drug: Decitabine; 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 decitabine when used concomitantly with filgrastim, cladribine, cytarabine, and mitoxantrone hydrochloride (G-CLAM) in patients with newly diagnosed acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS).

2. Compare, within the limits of a phase 1/2 study, the rate of complete remission without measurable residual disease (minimal residual disease negative [MRDneg] complete remission [CR]) with decitabine + G-CLAM at the MTD compared to similar patients treated previously with G-CLAM alone.

SECONDARY OBJECTIVES:

1. Evaluate, within the limits of a phase 1/2 study, disease response (complete remission, overall response rate) relapse-free survival (RFS), event-free survival (EFS), and overall survival (OS) in patients with newly-diagnosed AML / high-risk MDS.

2. Describe, within the limits of a phase 1/2 study, the toxicity profile of the study regimen.

OUTLINE: This is a dose de-escalation study of decitabine.

INDUCTION: Patients receive decitabine intravenously (IV) over 1 hour on days 1-10. Patients also receive filgrastim subcutaneously (SC) on days 0-5, cladribine IV over 2 hours on days 1-5, cytarabine IV over 2-4 hours on days 1-5, and mitoxantrone hydrochloride IV over 60 minutes on days 1-3.

RE-INDUCTION: Patients who do not achieve MRDneg CR after first induction are eligible for re-induction. Patients receive the same treatment as during induction except that decitabine is omitted.

CONSOLIDATION THERAPY: Beginning 6 weeks after achieving MRDneg CR or CR/CR with incomplete count recovery (CRi) after induction and/or re-induction, patients are eligible to receive filgrastim, cladribine, and cytarabine as in Induction. Treatment may be repeated for up to 4 courses in the absence of disease progression or unacceptable toxicity. Subsequent consolidation cycles would be given after recovery from the previous cycle (roughly 4-6 weeks).

After completion of study treatment, patients are followed up at for 1 month and every 3 months for up to 5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 1/2 Study of Concurrent Decitabine in Combination With G-CSF, Cladribine, Cytarabine, and Mitoxantrone (G-CLAM) in Adults With Newly Diagnosed Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndromes (MDS)
• Actual Study Start Date: Nov 17, 2016
• Actual Primary Completion Date: Oct 24, 2018
• Actual Study Completion Date: Oct 24, 2018

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (decitabine, G-CLAM) INDUCTION: Patients receive decitabine IV over 1 hour on days 1-10. Patients also receive filgrastim SC on days 0-5, cladribine IV over 2 hours on days 1-5, cytarabine IV over 2-4 hours on days 1-5, and mitoxantrone hydrochloride IV over 60 minutes on days 1-3. RE-INDUCTION: Patients who do not achieve MRDneg CR after first induction are eligible for re-induction. Patients receive the same treatment as during induction except that decitabine is omitted. CONSOLIDATION THERAPY: Beginning 6 weeks after achieving MRDneg CR or CR/CR with CRi after induction and/or re-induction, patients are eligible to receive filgrastim, cladribine, and cytarabine as in Induction. Treatment may be repeated for up to 4 courses in the absence of disease progression or unacceptable toxicity. Subsequent consolidation cycles would be given after recovery from the previous cycle (roughly 4-6 weeks).

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 Cytosine Arabinoside Cytosine-.beta.-arabinoside Cytosine-beta-arabinoside Erpalfa Starasid Tarabine PFS U 19920 U-19920 Udicil WR-28453 ; Drug: Decitabine; Given IV; Other Names: 5-Aza-2'-deoxycytidine Aza-TdC Dacogen Decitabine for Injection Deoxyazacytidine Dezocitidine ; Biological: Filgrastim; Given SC; Other Names: FILGRASTIM, LICENSE HOLDER UNSPECIFIED G-CSF Neupogen r-metHuG-CSF Recombinant Methionyl Human Granulocyte Colony Stimulating Factor rG-CSF Tevagrastim ; 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 Experiencing Dose Limiting Toxicities (DLTs) at the Maximum Tolerated Dose (MTD) for Decitabine When Given Together With G-CLAM Toxicities (DLTs) (Phase I) [Up to 49 days]

   Evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. MTD is defined as the highest dose studied in which the incidence of DLT is < 33%. Each participant was monitored for DLTs in the first 20 days of treatment. DLTs monitored included any grade 3 non-hematologic toxicity lasting more than 48 hours that resulted in more than a 7 day delay of the subsequent treatment cycle (except for febrile neutropenia or infection) any grade 4 or greater non-hematologic toxicity (except febrile neutropenia and infection unless a direct consequence of a treatment-related toxicity, and except constitutional symptoms if they recovered to grade 2 or less within 14 days) lack of recovery of the absolute neutrophil count to 500/microliter or greater and lack of self-sustained platelet count of at least 50,000/microliter by treatment day +49 with no evidence of residual leukemia

Secondary Outcome Measures

1. Number of Participants With Minimal Residual Disease Negative (MRDneg) Complete Remission (Phase II) [Up to 1 year]

   Compared to historical controls of filgrastim, cladribine, cytarabine, and mitoxantrone hydrochloride (G-CLAM) alone. A Simon Minimax two-stage design will be used.

2. Number of Participants Who Achieved Remission (Complete Remission [CR]/CR With Incomplete Peripheral Blood Count Recovery [CRi]) [Up to 1 year]

3. Number of Participants With Overall Survival [Up to 1 year]

4. Number of Participants With Relapse-free Survival [Up to 1 year]

5. Number of Participants With Event-free Survival [Up to 1 year]

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-grade" MDS (>= 10% blasts by morphology) or AML other than acute promyelocytic leukemia (APL) with t(15;17)(q22;q12) or variants according to the 2016 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 2003 recommendations of the International Working Group, requiring first or subsequent salvage therapy; patients with mixed phenotype acute leukemia (MPAL) 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

• Patients with prior autologous or allogeneic hematopoietic cell transplantation (HCT) 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 =< 9.2 as calculated with simplified model

• Should be off any active 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

• May have previously received monotherapy with demethylating agents for MDS or AML or treatment with a mitoxantrone- or cladribine-based regimen for MDS or AML, including G-CLAM, but not demethylating agent as priming for or in combination with chemotherapy

• Patients with symptoms/signs of hyperleukocytosis or white blood cells (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

• 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 registration)

• Serum creatinine =< 2.0 mg/dL (assessed within 14 days prior to registration)

• Left ventricular ejection fraction >= 45%, assessed within 3 months prior to registration, e.g. by multigated 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

• Ability to understand and willingness to sign a written 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 24-48 hours

• Known hypersensitivity to any study drug

• Pregnancy or lactation

• Patients may not be receiving any other investigational agents

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 and Statistical Analysis Plan - Oct 10, 2018

More Information

Publications

None provided.

• Responsible Party: Fred Hutchinson Cancer Center
• ClinicalTrials.gov Identifier: NCT02921061
• Other Study ID Numbers: 9713; NCI-2016-01401; 9713; P30CA015704; RG9216023
• First Posted: Sep 30, 2016
• Last Update Posted: Mar 17, 2020
• Last Verified: Jan 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Myelodysplastic Syndromes; Syndrome; Recurrence; Cytarabine; Decitabine; 2-chloro-3'-deoxyadenosine; Mitoxantrone; Cladribine; Lenograstim

Study Results

Participant Flow

Pre-assignment Detail	Though this is a dose escalation study, all patients ultimately received decitabine at the same dose (20 mg/m2) and the same additional drugs (G-CLAM) over the same dosing schedule.

Arm/Group Title	Treatment (Decitabine 20 mg/m2 and G-CLAM)
Arm/Group Description	Patients receive induction therapy comprising decitabine IV over 1 hour (20 mg/m2) on days 1-10 and G-CLAM (filgrastim SC on days 0-5, cladribine IV over 2 hours on days 1-5, cytarabine IV over 2-4 hours on days 1-5, and mitoxantrone IV over 60 minutes on days 1-3). Patients who do not achieve MRDneg CR after first induction are eligible for re-induction with G-CLAM. Beginning 6 weeks after achieving MRDneg CR or CR/CR with CRi after induction and/or re-induction, patients are eligible to receive consolidation therapy comprising GLCA (filgrastim, cladribine, cytarabine) for up to 4 cycles. Subsequent consolidation cycles would be given after recovery from the previous cycle (roughly 4-6 weeks).
Period Title: Overall Study
STARTED	28
COMPLETED	28
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (Decitabine 20 mg/m2 and G-CLAM)
Arm/Group Description	Patients receive induction therapy comprising decitabine IV over 1 hour (20 mg/m2) on days 1-10 and G-CLAM (filgrastim SC on days 0-5, cladribine IV over 2 hours on days 1-5, cytarabine IV over 2-4 hours on days 1-5, and mitoxantrone IV over 60 minutes on days 1-3). Patients who do not achieve MRDneg CR after first induction are eligible for re-induction with G-CLAM. Beginning 6 weeks after achieving MRDneg CR or CR/CR with CRi after induction and/or re-induction, patients are eligible to receive consolidation therapy comprising GLCA (filgrastim, cladribine, cytarabine) for up to 4 cycles. Subsequent consolidation cycles would be given after recovery from the previous cycle (roughly 4-6 weeks).
Overall Participants	28
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	67
Sex: Female, Male (Count of Participants)
Female	10 35.7%
Male	18 64.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 7.1%
Not Hispanic or Latino	26 92.9%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	3 10.7%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	25 89.3%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Experiencing Dose Limiting Toxicities (DLTs) at the Maximum Tolerated Dose (MTD) for Decitabine When Given Together With G-CLAM Toxicities (DLTs) (Phase I)
Description	Evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. MTD is defined as the highest dose studied in which the incidence of DLT is < 33%. Each participant was monitored for DLTs in the first 20 days of treatment. DLTs monitored included any grade 3 non-hematologic toxicity lasting more than 48 hours that resulted in more than a 7 day delay of the subsequent treatment cycle (except for febrile neutropenia or infection) any grade 4 or greater non-hematologic toxicity (except febrile neutropenia and infection unless a direct consequence of a treatment-related toxicity, and except constitutional symptoms if they recovered to grade 2 or less within 14 days) lack of recovery of the absolute neutrophil count to 500/microliter or greater and lack of self-sustained platelet count of at least 50,000/microliter by treatment day +49 with no evidence of residual leukemia
Time Frame	Up to 49 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Decitabine 20 mg/m2 and G-CLAM)
Arm/Group Description	Patients receive induction therapy comprising decitabine IV over 1 hour (20 mg/m2) on days 1-10 and G-CLAM (filgrastim SC on days 0-5, cladribine IV over 2 hours on days 1-5, cytarabine IV over 2-4 hours on days 1-5, and mitoxantrone IV over 60 minutes on days 1-3). Patients who do not achieve MRDneg CR after first induction are eligible for re-induction with G-CLAM. Beginning 6 weeks after achieving MRDneg CR or CR/CR with CRi after induction and/or re-induction, patients are eligible to receive consolidation therapy comprising GLCA (filgrastim, cladribine, cytarabine) for up to 4 cycles. Subsequent consolidation cycles would be given after recovery from the previous cycle (roughly 4-6 weeks).
Measure Participants	28
Count of Participants [Participants]	3 10.7%

2. Secondary Outcome

Title	Number of Participants With Minimal Residual Disease Negative (MRDneg) Complete Remission (Phase II)
Description	Compared to historical controls of filgrastim, cladribine, cytarabine, and mitoxantrone hydrochloride (G-CLAM) alone. A Simon Minimax two-stage design will be used.
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Decitabine 20 mg/m2 and G-CLAM)
Arm/Group Description	Patients receive induction therapy comprising decitabine IV over 1 hour (20 mg/m2) on days 1-10 and G-CLAM (filgrastim SC on days 0-5, cladribine IV over 2 hours on days 1-5, cytarabine IV over 2-4 hours on days 1-5, and mitoxantrone IV over 60 minutes on days 1-3). Patients who do not achieve MRDneg CR after first induction are eligible for re-induction with G-CLAM. Beginning 6 weeks after achieving MRDneg CR or CR/CR with CRi after induction and/or re-induction, patients are eligible to receive consolidation therapy comprising GLCA (filgrastim, cladribine, cytarabine) for up to 4 cycles. Subsequent consolidation cycles would be given after recovery from the previous cycle (roughly 4-6 weeks).
Measure Participants	28
Number [participants]	13 46.4%

3. Secondary Outcome

Title	Number of Participants Who Achieved Remission (Complete Remission [CR]/CR With Incomplete Peripheral Blood Count Recovery [CRi])
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Decitabine 20 mg/m2 and G-CLAM)
Arm/Group Description	Patients receive induction therapy comprising decitabine IV over 1 hour (20 mg/m2) on days 1-10 and G-CLAM (filgrastim SC on days 0-5, cladribine IV over 2 hours on days 1-5, cytarabine IV over 2-4 hours on days 1-5, and mitoxantrone IV over 60 minutes on days 1-3). Patients who do not achieve MRDneg CR after first induction are eligible for re-induction with G-CLAM. Beginning 6 weeks after achieving MRDneg CR or CR/CR with CRi after induction and/or re-induction, patients are eligible to receive consolidation therapy comprising GLCA (filgrastim, cladribine, cytarabine) for up to 4 cycles. Subsequent consolidation cycles would be given after recovery from the previous cycle (roughly 4-6 weeks).
Measure Participants	28
Number [participants]	13 46.4%

4. Secondary Outcome

Title	Number of Participants With Overall Survival
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Decitabine 20 mg/m2 and G-CLAM)
Arm/Group Description	Patients receive induction therapy comprising decitabine IV over 1 hour (20 mg/m2) on days 1-10 and G-CLAM (filgrastim SC on days 0-5, cladribine IV over 2 hours on days 1-5, cytarabine IV over 2-4 hours on days 1-5, and mitoxantrone IV over 60 minutes on days 1-3). Patients who do not achieve MRDneg CR after first induction are eligible for re-induction with G-CLAM. Beginning 6 weeks after achieving MRDneg CR or CR/CR with CRi after induction and/or re-induction, patients are eligible to receive consolidation therapy comprising GLCA (filgrastim, cladribine, cytarabine) for up to 4 cycles. Subsequent consolidation cycles would be given after recovery from the previous cycle (roughly 4-6 weeks).
Measure Participants	28
Number [participants]	9 32.1%

5. Secondary Outcome

Title	Number of Participants With Relapse-free Survival
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Decitabine 20 mg/m2 and G-CLAM)
Arm/Group Description	Patients receive induction therapy comprising decitabine IV over 1 hour (20 mg/m2) on days 1-10 and G-CLAM (filgrastim SC on days 0-5, cladribine IV over 2 hours on days 1-5, cytarabine IV over 2-4 hours on days 1-5, and mitoxantrone IV over 60 minutes on days 1-3). Patients who do not achieve MRDneg CR after first induction are eligible for re-induction with G-CLAM. Beginning 6 weeks after achieving MRDneg CR or CR/CR with CRi after induction and/or re-induction, patients are eligible to receive consolidation therapy comprising GLCA (filgrastim, cladribine, cytarabine) for up to 4 cycles. Subsequent consolidation cycles would be given after recovery from the previous cycle (roughly 4-6 weeks).
Measure Participants	28
Number [participants]	8 28.6%

6. Secondary Outcome

Title	Number of Participants With Event-free Survival
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Decitabine 20 mg/m2 and G-CLAM)
Arm/Group Description	Patients receive induction therapy comprising decitabine IV over 1 hour (20 mg/m2) on days 1-10 and G-CLAM (filgrastim SC on days 0-5, cladribine IV over 2 hours on days 1-5, cytarabine IV over 2-4 hours on days 1-5, and mitoxantrone IV over 60 minutes on days 1-3). Patients who do not achieve MRDneg CR after first induction are eligible for re-induction with G-CLAM. Beginning 6 weeks after achieving MRDneg CR or CR/CR with CRi after induction and/or re-induction, patients are eligible to receive consolidation therapy comprising GLCA (filgrastim, cladribine, cytarabine) for up to 4 cycles. Subsequent consolidation cycles would be given after recovery from the previous cycle (roughly 4-6 weeks).
Measure Participants	28
Number [participants]	8 28.6%

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 duration of about 10 days concluded
Arm/Group Title	Treatment (Decitabine 20 mg/m2 and G-CLAM)
Arm/Group Description	Patients receive induction therapy comprising decitabine IV over 1 hour (20 mg/m2) on days 1-10 and G-CLAM (filgrastim SC on days 0-5, cladribine IV over 2 hours on days 1-5, cytarabine IV over 2-4 hours on days 1-5, and mitoxantrone IV over 60 minutes on days 1-3). Patients who do not achieve MRDneg CR after first induction are eligible for re-induction with G-CLAM. Beginning 6 weeks after achieving MRDneg CR or CR/CR with CRi after induction and/or re-induction, patients are eligible to receive consolidation therapy comprising GLCA (filgrastim, cladribine, cytarabine) for up to 4 cycles. Subsequent consolidation cycles would be given after recovery from the previous cycle (roughly 4-6 weeks).
All Cause Mortality
	Treatment (Decitabine 20 mg/m2 and G-CLAM)
	Affected / at Risk (%)	# Events
Total	19/28 (67.9%)
Serious Adverse Events
	Treatment (Decitabine 20 mg/m2 and G-CLAM)
	Affected / at Risk (%)	# Events
Total	2/28 (7.1%)
Cardiac disorders
Cardiogenic shock/heart failure	1/28 (3.6%)
Infections and infestations
Sepsis	1/28 (3.6%)
Other (Not Including Serious) Adverse Events
	Treatment (Decitabine 20 mg/m2 and G-CLAM)
	Affected / at Risk (%)	# Events
Total	28/28 (100%)
Blood and lymphatic system disorders
hyperbilirubinemia, grade 4	1/28 (3.6%)
Cardiac disorders
aortic valve disease, grade 3	1/28 (3.6%)
atrial fibrillation, grade 3	2/28 (7.1%)
atrial fibrillation, grade 4	1/28 (3.6%)
infective endocarditis, grade 3	1/28 (3.6%)
myocardial infarction, grade 4	1/28 (3.6%)
Gastrointestinal disorders
diarrhea, grade 3	2/28 (7.1%)
duodenal hemorrhage, grade 4	1/28 (3.6%)
General disorders
back pain, grade 3	1/28 (3.6%)
fatigue, grade 3	1/28 (3.6%)
hypertension, grade 3	2/28 (7.1%)
hypotension, grade 3	1/28 (3.6%)
hypoxemia, grade 3	7/28 (25%)
LV systolic dysfunction, grade 4	1/28 (3.6%)
nausea, grade 3	1/28 (3.6%)
sinusitis, grade 3	1/28 (3.6%)
syncope, grade 3	3/28 (10.7%)
tumor lysis syndrome, grade 3	2/28 (7.1%)
Hepatobiliary disorders
AST increased, grade 3	1/28 (3.6%)
Infections and infestations
febrile neutropenia, grade 3	27/28 (96.4%)
Metabolism and nutrition disorders
hypokalemia, grade 3	2/28 (7.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
encephalopathy, grade 4	1/28 (3.6%)
Psychiatric disorders
delirium, grade 3	1/28 (3.6%)
Renal and urinary disorders
acute kidney injury, grade 3	1/28 (3.6%)
Respiratory, thoracic and mediastinal disorders
dyspnea, grade 4	1/28 (3.6%)
pleural effusions, grade 3	1/28 (3.6%)
pulmonary nodules, grade 3	7/28 (25%)
Skin and subcutaneous tissue disorders
maculopapular rash, grade 3	1/28 (3.6%)
Vascular disorders
phlebitis infective, grade 3	1/28 (3.6%)

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.