Clofarabine, Idarubicin, and Cytarabine (CIA) Versus Fludarabine, Idarubicin, and Cytarabine (FLAI) in Acute Myelogenous Leukemia (AML) and High-Risk Myelodysplastic Syndrome

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01289457
• Collaborator: (none)
• Enrollment: 282
• Location: 1
• Arms: 3
• Actual Duration (Months): 76.8
• Patients Per Site Per Month: 3.7

Study Details

Study Description

Brief Summary

The goal of this clinical research study is to learn if the combination of clofarabine, idarubicin, and cytarabine, or the combination of fludarabine, idarubicin, and cytarabine can help control Acute myeloid leukemia (AML) and Myelodysplastic syndromes (MDS). The safety of these study drug combinations will also be studied.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Drug: Clofarabine; Drug: Idarubicin; Drug: Cytarabine; Drug: Fludarabine	Phase 1/Phase 2

Detailed Description

The Study Drugs:

Clofarabine is designed to interfere with the growth and development of cancer cells.

Idarubicin is designed to cause breaks in both strands of DNA (the genetic material of cells). This may cause the cancer cells to die.

Cytarabine and Fludarabine are designed to insert themselves into the DNA of cancer cells and stop the DNA from repairing itself.

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you join this study. Up to 4 groups of 6 participants will be enrolled in the Phase I portion of the study. Up to 280 participants will be enrolled in Phase II.

Phase I:

If you are enrolled in the Phase I portion, the dose of clofarabine you receive will depend on when you joined this study. The first group of participants will receive the lowest dose level of clofarabine. Each new group will receive a higher dose of clofarabine than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of clofarabine is found.

All participants will receive the same dose level of idarubicin and cytarabine.

Phase II:

If you are enrolled in the Phase II portion, you will be randomly assigned (as in the flip of a coin) to 1 of 2 groups:

• If you are in Group 1, you will receive clofarabine, idarubicin, and cytarabine. You will receive clofarabine at the highest dose that was tolerated in the Phase I portion.

• If you are in Group 2, you will receive fludarabine, idarubicin, and cytarabine.

Study Drug Administration:

Study drug(s) will be given in what are called "cycles." Each cycle is 28 days.

Phase I:

On Days 1-5:

• You will receive clofarabine by vein over about 1 hour.

• You will receive cytarabine by vein over about 2 hours.

• On Days 1-3 only, you will receive idarubicin by vein over about 30 minutes.

Phase II (Induction):

The first cycle of study drugs is called Induction. If the doctor thinks it is needed, you will have up to 2 Induction cycles.

If you are in Group 1:

On Days 1-5 of each cycle:

• You will receive clofarabine by vein over about 1 hour.

• You will receive cytarabine by vein over about 2 hours.

• On Days 1-3 only, you will receive idarubicin by vein over about 30 minutes.

If you are in Group 2:

On Days 1-5 of each cycle:

• You will receive fludarabine by vein over about 30 minutes.

• You will receive cytarabine by vein over about 2 hours.

• On Days 1-3 only, you will receive idarubicin by vein over about 30 minutes.

If the doctor thinks it is needed, you may receive less than 5 days of treatment in the induction cycle.

If the doctor thinks it is needed, your dose level will be reduced after Induction.

Phase II (Consolidation):

If the disease responds to the study drugs, you may receive up to 6 more cycles of study drugs. This is called Consolidation.

If you are in Group 1:

On Days 1-3 of each cycle :

• You will receive clofarabine by vein over about 1 hour.

• You will receive cytarabine by vein over about 2 hours.

• After 1 to 2 hours of receiving cytarabine on Days 1-2 only, you will receive idarubicin by vein over about 30 minutes.

If you are in Group 2:

On Days 1-3 of each cycle:

• You will receive fludarabine by vein over about 30 minutes

• You will receive cytarabine by vein over about 2 hours.

• After 1 to 2 hours of receiving cytarabine on Days 1-2 only, you will receive idarubicin by vein over about 30 minutes

If the cancer does not completely respond after Cycle 1, you may repeat induction (Cycle 1). If the cancer completely responds, you will begin the consolidation cycles.

If the doctor thinks it is needed, you may receive less than 3 days of treatment in the consolidation cycles.

Study Visits:

You will have a physical exam, including measurement of your vital signs before the start of each cycle. Blood (about 2 teaspoons) will be drawn for routine tests every 3-7 days.

On Day 28 of every 2-3 cycles (+/- 7 days), if the doctor thinks it is needed, you will have a bone marrow aspirate to check the status of the disease. To collect a bone marrow aspirate, an area of the hip is numbed with anesthetic, and a small amount of bone marrow is withdrawn through a large needle.

Length of Study:

You may continue taking the study drugs for as long as the doctor thinks it is in your best interest or up to 8 total cycles. You will no longer be able to take the study drugs if the disease gets worse or intolerable side effects occur.

Your participation on the study will be over once you have completed the long-term follow-up.

Long-Term Follow-up:

Every 3 months for 1 year after you are off study, you will be called and asked how you are feeling, about any side effects you may be having, and about any other drugs you may be taking. These calls should last about 5 minutes each.

This is an investigational study. Cytarabine and Idarubicin are FDA approved and commercially available for the treatment of AML. Fludarabine is FDA approved and commercially available for the treatment of chronic lymphocytic leukemia (CLL). Clofarabine is FDA approved and commercially available for the treatment of acute lymphoblastic leukemia (ALL). The combination of these study drugs is investigational.

Up to 292 patients will take part in Phase I and Phase II of this study. All will be enrolled at MD Anderson.

Study Design

• Study Type: Interventional
• Actual Enrollment: 282 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I/II Randomized Study of Clofarabine, Idarubicin, and Cytarabine (CIA) Versus Fludarabine, Idarubicin, and Cytarabine (FLAI) in Acute Myelogenous Leukemia and High-Risk Myelodysplastic Syndrome
• Actual Study Start Date: Feb 2, 2011
• Actual Primary Completion Date: Jun 28, 2017
• Actual Study Completion Date: Jun 28, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Clofarabine + Idarubicin + Cytarabine Phase I: Clofarabine Starting dose 15 mg/m2 by vein for 5 days (days 1-5) + Idarubicin 10 mg/m2 by vein on day 1-3 + Cytarabine 1 g/m2 by vein on day 1-5.	Drug: Clofarabine; Phase I: 15 mg/m2 by vein (IV) daily for 5 days of a 28 day cycle. Phase II: Clofarabine (dose selected based on Phase I portion) by vein over approximately 1 hour daily for 5 days (days 1-5) for a 28 day cycle.; Other Names: Clofarex Clolar ; Drug: Idarubicin; 10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 1-3) of a 28 day cycle.; Other Names: Idamycin ; Drug: Cytarabine; 1 g/m2 by vein over approximately 2 hours daily for 5 days (days 1-5) for a 28 day cycle.; Other Names: Ara-C Cytosar DepoCyt Cytosine Arabinosine Hydrochloride ; Drug: Fludarabine; 30 mg/m2 by vein over approximately 30 minutes daily for 5 days (days 1-5).; Other Names: Fludara
Experimental: Group 1 CIA Phase II, Group 1 CIA (Clofarabine + Idarubicin + Cytarabine): Clofarabine Maximum Tolerated Dose (MTD) based on Phase I by vein on days 1-5; Idarubicin 10 mg/m2 by vein on days 1-3; Cytarabine 1 g/m2 by vein on days 1-5.	Drug: Clofarabine; Phase I: 15 mg/m2 by vein (IV) daily for 5 days of a 28 day cycle. Phase II: Clofarabine (dose selected based on Phase I portion) by vein over approximately 1 hour daily for 5 days (days 1-5) for a 28 day cycle.; Other Names: Clofarex Clolar ; Drug: Idarubicin; 10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 1-3) of a 28 day cycle.; Other Names: Idamycin ; Drug: Cytarabine; 1 g/m2 by vein over approximately 2 hours daily for 5 days (days 1-5) for a 28 day cycle.; Other Names: Ara-C Cytosar DepoCyt Cytosine Arabinosine Hydrochloride
Experimental: Group 2 FLAI Phase II, Group 2 FLAI (Fludarabine + Idarubicin + Cytarabine): Fludarabine 30 mg/m2 by vein on days 1-5; Idarubicin 10 mg/m2 by vein on days 1-3; Cytarabine 1 g/m2 by vein on days 1-5.	Drug: Idarubicin; 10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 1-3) of a 28 day cycle.; Other Names: Idamycin ; Drug: Cytarabine; 1 g/m2 by vein over approximately 2 hours daily for 5 days (days 1-5) for a 28 day cycle.; Other Names: Ara-C Cytosar DepoCyt Cytosine Arabinosine Hydrochloride ; Drug: Fludarabine; 30 mg/m2 by vein over approximately 30 minutes daily for 5 days (days 1-5).; Other Names: Fludara

Outcome Measures

Primary Outcome Measures

1. Maximum Tolerated Dose (MTD) of Clofarabine, Idarubicin, and Cytarabine [28 days]

   MTD is highest dose level in which <2 patients of 6 develop first cycle dose limiting toxicities (DLT). Toxicity defined as any treatment-related grade 3 or greater non-hematological toxicities.

Secondary Outcome Measures

1. Response Rates of Clofarabine, Idarubicin, and Cytarabine (CIA) Versus Fludarabine, Idarubicin, and Cytarabine (FLAI) [12 months]

   NCI & Myelodysplastic syndromes (MDS) International Working Group (IWG) Definitions: Complete Response (CR): Neutrophil count ≥1.0 ×10^9/L, Platelet count ≥100 ×10^9/L, Bone marrow aspirate </=5% blasts, No extramedullary leukemia; CRi: Response as in CR but platelets <100 ×10^9/L; Partial response (PR): Neutrophil count ≥ 1.0 ×10^9/L, Platelet count ≥100 ×10^9/L, ≥ 50% reduction in bone marrow blasts over baseline; Clinical benefit: In addition to IWG criteria, in AML, a decrease in bone marrow blasts to <5% is also considered clinical benefit; Stable Disease: In addition to IWG criteria and in absence any of above response criteria, stable disease considered if the bone marrow blast percent does not increase compared to pretreatment level; Relapse: Increase of bone marrow blasts to >10% after initial response. Response assessed Day 28 of every 2-3 cycles during treatment.

2. Event-Free Survival (EFS) at 2 Years [Up to 2 years or until relapse/death]

   Comparison of the event-free survival (EFS) between treatment CIA and FLAI, where an event is defined to be resistance to treatment, relapse (after response) or death, whichever occurred first.

3. Overall Survival [up to 2 years]

   Time from date of treatment start until date of death due to any cause or last Follow-up.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Sign an Institutional Review Board (IRB)-approved informed consent document.

2. Age 18 to 60. Patients above the age of 60 only with principal investigator (PI) approval

3. Diagnosis of newly diagnosed AML [other than acute promyelocytic leukemia (APL)] or high-risk (intermediate-2 or high by International Prostate Symptom Score (IPSS) or > 10% blasts, including CMML) MDS. Prior therapy with hydrea and the use of a single or a two day dose of cytarabine (up to 3 g/m2) for emergency use up to 24 hours prior to start of study therapy is allowed. Prior therapy for MDS or other AHD is not allowed.

4. Eastern Cooperative Oncology Group (ECOG) performance status of </= 3 at study entry.

5. Organ function as defined below (unless due to leukemia): Serum creatinine </= 3 mg/dL Total bilirubin </= 2.5 mg/dL , Alanine aminotransferase (ALT) (SGPT) </= 3 * upper limit of normal (ULN) or </= 5 * ULN if related to disease.

6. Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days and must agree to practice acceptable contraceptive methods. Men must agree not to father a child and agree to use a condom if his partner is of child bearing potential.

7. Cardiac ejection fraction >/= 40% (by either cardiac echo or multiple gated acquisition scan (MUGA) scan). Documentation of recent (</= 6 months from screening) outside reports is acceptable.

Exclusion Criteria:

1. Breast feeding females

2. Patients with uncontrolled active infections (viral, bacterial, and fungal are not eligible).

3. Patients with active secondary malignancy will not be eligible.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center

Investigators

• Principal Investigator: Elias Jabbour, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 10, 2013

More Information

Additional Information:

• University of Texas MD Anderson Cancer Center Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT01289457
• Other Study ID Numbers: 2010-0788; NCI-2011-00251
• First Posted: Feb 3, 2011
• Last Update Posted: Feb 24, 2020
• Last Verified: Feb 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by M.D. Anderson Cancer Center: Acute Myelogenous Leukemia; AML; High-Risk Myelodysplastic Syndrome; MDS; Relapsed; Refractory; Clofarabine; Clofarex; Clolar; Idarubicin; Idamycin; Cytarabine; Ara-C; Cytosar; DepoCyt; Cytosine Arabinosine Hydrochloride
• Additional relevant MeSH terms: Leukemia; Preleukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Cytarabine; Fludarabine; Idarubicin; Clofarabine

Study Results

Participant Flow

Arm/Group Title	Clofarabine + Idarubicin + Cytarabine	Group 1 CIA	Group 2 FLAI
Arm/Group Description	Phase I: Clofarabine Starting dose 15 mg/m2 by vein for 5 days (days 1-5) + Idarubicin 10 mg/m2 by vein on day 1-3 + Cytarabine 1 g/m2 by vein on day 1-5. Clofarabine: Phase I: 15 mg/m2 by vein (IV) daily for 5 days of a 28 day cycle. Phase II: Clofarabine (dose selected based on Phase I portion) by vein over approximately 1 hour daily for 5 days (days 1-5) for a 28 day cycle. Idarubicin: 10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 1-3) of a 28 day cycle. Cytarabine: 1 g/m2 by vein over approximately 2 hours daily for 5 days (days 1-5) for a 28 day cycle.	Phase II, Group 1 CIA (Clofarabine + Idarubicin + Cytarabine): Clofarabine MTD based on Phase I by vein on days 1-5; Idarubicin 10 mg/m2 by vein on days 1-3; Cytarabine 1 g/m2 by vein on days 1-5. Clofarabine: Phase I: 15 mg/m2 by vein (IV) daily for 5 days of a 28 day cycle. Phase II: Clofarabine (dose selected based on Phase I portion) by vein over approximately 1 hour daily for 5 days (days 1-5) for a 28 day cycle. Idarubicin: 10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 1-3) of a 28 day cycle. Cytarabine: 1 g/m2 by vein over approximately 2 hours daily for 5 days (days 1-5) for a 28 day cycle.	Phase II, Group 2 FLAI (Fludarabine + Idarubicin + Cytarabine): Fludarabine 30 mg/m2 by vein on days 1-5; Idarubicin 10 mg/m2 by vein on days 1-3; Cytarabine 1 g/m2 by vein on days 1-5. Idarubicin: 10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 1-3) of a 28 day cycle. Cytarabine: 1 g/m2 by vein over approximately 2 hours daily for 5 days (days 1-5) for a 28 day cycle. Fludarabine: 30 mg/m2 by vein over approximately 30 minutes daily for 5 days (days 1-5).
Period Title: Overall Study
STARTED	12	157	113
COMPLETED	12	157	113
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Clofarabine + Idarubicin + Cytarabine	Group 1 CIA	Group 2 FLAI	Total
Arm/Group Description	Phase I: Clofarabine Starting dose 15 mg/m2 by vein for 5 days (days 1-5) + Idarubicin 10 mg/m2 by vein on day 1-3 + Cytarabine 1 g/m2 by vein on day 1-5. Clofarabine: Phase I: 15 mg/m2 by vein (IV) daily for 5 days of a 28 day cycle. Phase II: Clofarabine (dose selected based on Phase I portion) by vein over approximately 1 hour daily for 5 days (days 1-5) for a 28 day cycle. Idarubicin: 10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 1-3) of a 28 day cycle. Cytarabine: 1 g/m2 by vein over approximately 2 hours daily for 5 days (days 1-5) for a 28 day cycle.	Phase II, Group 1 CIA (Clofarabine + Idarubicin + Cytarabine): Clofarabine MTD based on Phase I by vein on days 1-5; Idarubicin 10 mg/m2 by vein on days 1-3; Cytarabine 1 g/m2 by vein on days 1-5. Clofarabine: Phase I: 15 mg/m2 by vein (IV) daily for 5 days of a 28 day cycle. Phase II: Clofarabine (dose selected based on Phase I portion) by vein over approximately 1 hour daily for 5 days (days 1-5) for a 28 day cycle. Idarubicin: 10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 1-3) of a 28 day cycle. Cytarabine: 1 g/m2 by vein over approximately 2 hours daily for 5 days (days 1-5) for a 28 day cycle.	Phase II, Group 2 FLAI (Fludarabine + Idarubicin + Cytarabine): Fludarabine 30 mg/m2 by vein on days 1-5; Idarubicin 10 mg/m2 by vein on days 1-3; Cytarabine 1 g/m2 by vein on days 1-5. Idarubicin: 10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 1-3) of a 28 day cycle. Cytarabine: 1 g/m2 by vein over approximately 2 hours daily for 5 days (days 1-5) for a 28 day cycle. Fludarabine: 30 mg/m2 by vein over approximately 30 minutes daily for 5 days (days 1-5).	Total of all reporting groups
Overall Participants	12	157	113	282
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	11 91.7%	153 97.5%	108 95.6%	272 96.5%
>=65 years	1 8.3%	4 2.5%	5 4.4%	10 3.5%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	52	53	51	53
Sex: Female, Male (Count of Participants)
Female	6 50%	74 47.1%	55 48.7%	135 47.9%
Male	6 50%	83 52.9%	58 51.3%	147 52.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	1 8.3%	6 3.8%	6 5.3%	13 4.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	3 25%	20 12.7%	11 9.7%	34 12.1%
White	8 66.7%	122 77.7%	85 75.2%	215 76.2%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	9 5.7%	11 9.7%	20 7.1%
Region of Enrollment (participants) [Number]
United States	12 100%	157 100%	113 100%	282 100%

Outcome Measures

1. Primary Outcome

Title	Maximum Tolerated Dose (MTD) of Clofarabine, Idarubicin, and Cytarabine
Description	MTD is highest dose level in which <2 patients of 6 develop first cycle dose limiting toxicities (DLT). Toxicity defined as any treatment-related grade 3 or greater non-hematological toxicities.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

Maximum Tolerated Dose (MTD) is only reported for the Phase I portion of the study. MTD was not done on the Phase II portion of the study and therefore, PhII Groups 1 and 2 do not have results for MTD.

Arm/Group Title	Clofarabine + Idarubicin + Cytarabine	Group 1 CIA	Group 2 FLAI
Arm/Group Description	Phase I: Clofarabine Starting dose 15 mg/m2 by vein for 5 days (days 1-5) + Idarubicin 10 mg/m2 by vein on day 1-3 + Cytarabine 1 g/m2 by vein on day 1-5. Clofarabine: Phase I: 15 mg/m2 by vein (IV) daily for 5 days of a 28 day cycle. Phase II: Clofarabine (dose selected based on Phase I portion) by vein over approximately 1 hour daily for 5 days (days 1-5) for a 28 day cycle. Idarubicin: 10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 1-3) of a 28 day cycle. Cytarabine: 1 g/m2 by vein over approximately 2 hours daily for 5 days (days 1-5) for a 28 day cycle.	Phase II, Group 1 CIA (Clofarabine + Idarubicin + Cytarabine): Clofarabine MTD based on Phase I by vein on days 1-5; Idarubicin 10 mg/m2 by vein on days 1-3; Cytarabine 1 g/m2 by vein on days 1-5. Clofarabine: Phase I: 15 mg/m2 by vein (IV) daily for 5 days of a 28 day cycle. Phase II: Clofarabine (dose selected based on Phase I portion) by vein over approximately 1 hour daily for 5 days (days 1-5) for a 28 day cycle. Idarubicin: 10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 1-3) of a 28 day cycle. Cytarabine: 1 g/m2 by vein over approximately 2 hours daily for 5 days (days 1-5) for a 28 day cycle.	Phase II, Group 2 FLAI (Fludarabine + Idarubicin + Cytarabine): Fludarabine 30 mg/m2 by vein on days 1-5; Idarubicin 10 mg/m2 by vein on days 1-3; Cytarabine 1 g/m2 by vein on days 1-5. Idarubicin: 10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 1-3) of a 28 day cycle. Cytarabine: 1 g/m2 by vein over approximately 2 hours daily for 5 days (days 1-5) for a 28 day cycle. Fludarabine: 30 mg/m2 by vein over approximately 30 minutes daily for 5 days (days 1-5).
Measure Participants	12	0	0
Number [mg/m^2]	15

2. Secondary Outcome

Title	Response Rates of Clofarabine, Idarubicin, and Cytarabine (CIA) Versus Fludarabine, Idarubicin, and Cytarabine (FLAI)
Description	NCI & Myelodysplastic syndromes (MDS) International Working Group (IWG) Definitions: Complete Response (CR): Neutrophil count ≥1.0 ×10^9/L, Platelet count ≥100 ×10^9/L, Bone marrow aspirate </=5% blasts, No extramedullary leukemia; CRi: Response as in CR but platelets <100 ×10^9/L; Partial response (PR): Neutrophil count ≥ 1.0 ×10^9/L, Platelet count ≥100 ×10^9/L, ≥ 50% reduction in bone marrow blasts over baseline; Clinical benefit: In addition to IWG criteria, in AML, a decrease in bone marrow blasts to <5% is also considered clinical benefit; Stable Disease: In addition to IWG criteria and in absence any of above response criteria, stable disease considered if the bone marrow blast percent does not increase compared to pretreatment level; Relapse: Increase of bone marrow blasts to >10% after initial response. Response assessed Day 28 of every 2-3 cycles during treatment.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

The outcome measure for for the Phase I portion of this study was to determine MTD only. Data Was not collected for Response Rate for the Phase I arm of this study.

Arm/Group Title	Clofarabine + Idarubicin + Cytarabine	Group 1 CIA	Group 2 FLAI
Arm/Group Description	Phase I: Clofarabine Starting dose 15 mg/m2 by vein for 5 days (days 1-5) + Idarubicin 10 mg/m2 by vein on day 1-3 + Cytarabine 1 g/m2 by vein on day 1-5. Clofarabine: Phase I: 15 mg/m2 by vein (IV) daily for 5 days of a 28 day cycle. Phase II: Clofarabine (dose selected based on Phase I portion) by vein over approximately 1 hour daily for 5 days (days 1-5) for a 28 day cycle. Idarubicin: 10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 1-3) of a 28 day cycle. Cytarabine: 1 g/m2 by vein over approximately 2 hours daily for 5 days (days 1-5) for a 28 day cycle.	Phase II, Group 1 CIA (Clofarabine + Idarubicin + Cytarabine): Clofarabine MTD based on Phase I by vein on days 1-5; Idarubicin 10 mg/m2 by vein on days 1-3; Cytarabine 1 g/m2 by vein on days 1-5. Clofarabine: Phase I: 15 mg/m2 by vein (IV) daily for 5 days of a 28 day cycle. Phase II: Clofarabine (dose selected based on Phase I portion) by vein over approximately 1 hour daily for 5 days (days 1-5) for a 28 day cycle. Idarubicin: 10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 1-3) of a 28 day cycle. Cytarabine: 1 g/m2 by vein over approximately 2 hours daily for 5 days (days 1-5) for a 28 day cycle.	Phase II, Group 2 FLAI (Fludarabine + Idarubicin + Cytarabine): Fludarabine 30 mg/m2 by vein on days 1-5; Idarubicin 10 mg/m2 by vein on days 1-3; Cytarabine 1 g/m2 by vein on days 1-5. Idarubicin: 10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 1-3) of a 28 day cycle. Cytarabine: 1 g/m2 by vein over approximately 2 hours daily for 5 days (days 1-5) for a 28 day cycle. Fludarabine: 30 mg/m2 by vein over approximately 30 minutes daily for 5 days (days 1-5).
Measure Participants	0	157	113
Count of Participants [Participants]	107 891.7%	76 48.4%

3. Secondary Outcome

Title	Event-Free Survival (EFS) at 2 Years
Description	Comparison of the event-free survival (EFS) between treatment CIA and FLAI, where an event is defined to be resistance to treatment, relapse (after response) or death, whichever occurred first.
Time Frame	Up to 2 years or until relapse/death

Outcome Measure Data

Analysis Population Description

The outcome measure for for the Phase I portion of this study was to determine MTD only. Data Was not collected for EFS for the Phase I arm of this study.

Arm/Group Title	Clofarabine + Idarubicin + Cytarabine	Group 1 CIA	Group 2 FLAI
Arm/Group Description	Phase I: Clofarabine Starting dose 15 mg/m2 by vein for 5 days (days 1-5) + Idarubicin 10 mg/m2 by vein on day 1-3 + Cytarabine 1 g/m2 by vein on day 1-5. Clofarabine: Phase I: 15 mg/m2 by vein (IV) daily for 5 days of a 28 day cycle. Phase II: Clofarabine (dose selected based on Phase I portion) by vein over approximately 1 hour daily for 5 days (days 1-5) for a 28 day cycle. Idarubicin: 10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 1-3) of a 28 day cycle. Cytarabine: 1 g/m2 by vein over approximately 2 hours daily for 5 days (days 1-5) for a 28 day cycle.	Phase II, Group 1 CIA (Clofarabine + Idarubicin + Cytarabine): Clofarabine MTD based on Phase I by vein on days 1-5; Idarubicin 10 mg/m2 by vein on days 1-3; Cytarabine 1 g/m2 by vein on days 1-5. Clofarabine: Phase I: 15 mg/m2 by vein (IV) daily for 5 days of a 28 day cycle. Phase II: Clofarabine (dose selected based on Phase I portion) by vein over approximately 1 hour daily for 5 days (days 1-5) for a 28 day cycle. Idarubicin: 10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 1-3) of a 28 day cycle. Cytarabine: 1 g/m2 by vein over approximately 2 hours daily for 5 days (days 1-5) for a 28 day cycle.	Phase II, Group 2 FLAI (Fludarabine + Idarubicin + Cytarabine): Fludarabine 30 mg/m2 by vein on days 1-5; Idarubicin 10 mg/m2 by vein on days 1-3; Cytarabine 1 g/m2 by vein on days 1-5. Idarubicin: 10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 1-3) of a 28 day cycle. Cytarabine: 1 g/m2 by vein over approximately 2 hours daily for 5 days (days 1-5) for a 28 day cycle. Fludarabine: 30 mg/m2 by vein over approximately 30 minutes daily for 5 days (days 1-5).
Measure Participants	0	157	113
Median (Full Range) [Months]	7.1	8.4

4. Secondary Outcome

Title	Overall Survival
Description	Time from date of treatment start until date of death due to any cause or last Follow-up.
Time Frame	up to 2 years

Outcome Measure Data

Analysis Population Description

The outcome measure for the Phase I portion of this study was to determine MTD only. Data Was not collected for Overall Survival for the Phase I arm of this study.

Arm/Group Title	Clofarabine + Idarubicin + Cytarabine	Group 1 CIA	Group 2 FLAI
Arm/Group Description	Phase I: Clofarabine Starting dose 15 mg/m2 by vein for 5 days (days 1-5) + Idarubicin 10 mg/m2 by vein on day 1-3 + Cytarabine 1 g/m2 by vein on day 1-5. Clofarabine: Phase I: 15 mg/m2 by vein (IV) daily for 5 days of a 28 day cycle. Phase II: Clofarabine (dose selected based on Phase I portion) by vein over approximately 1 hour daily for 5 days (days 1-5) for a 28 day cycle. Idarubicin: 10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 1-3) of a 28 day cycle. Cytarabine: 1 g/m2 by vein over approximately 2 hours daily for 5 days (days 1-5) for a 28 day cycle.	Phase II, Group 1 CIA (Clofarabine + Idarubicin + Cytarabine): Clofarabine MTD based on Phase I by vein on days 1-5; Idarubicin 10 mg/m2 by vein on days 1-3; Cytarabine 1 g/m2 by vein on days 1-5. Clofarabine: Phase I: 15 mg/m2 by vein (IV) daily for 5 days of a 28 day cycle. Phase II: Clofarabine (dose selected based on Phase I portion) by vein over approximately 1 hour daily for 5 days (days 1-5) for a 28 day cycle. Idarubicin: 10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 1-3) of a 28 day cycle. Cytarabine: 1 g/m2 by vein over approximately 2 hours daily for 5 days (days 1-5) for a 28 day cycle.	Phase II, Group 2 FLAI (Fludarabine + Idarubicin + Cytarabine): Fludarabine 30 mg/m2 by vein on days 1-5; Idarubicin 10 mg/m2 by vein on days 1-3; Cytarabine 1 g/m2 by vein on days 1-5. Idarubicin: 10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 1-3) of a 28 day cycle. Cytarabine: 1 g/m2 by vein over approximately 2 hours daily for 5 days (days 1-5) for a 28 day cycle. Fludarabine: 30 mg/m2 by vein over approximately 30 minutes daily for 5 days (days 1-5).
Measure Participants	0	157	113
Median (Full Range) [Months]	14.5	15.1

Adverse Events

Time Frame	up to 1 year
Arm/Group Title	Clofarabine + Idarubicin + Cytarabine		Group 1 CIA		Group 2 FLAI
Arm/Group Description	Phase I: Clofarabine Starting dose 15 mg/m2 by vein for 5 days (days 1-5) + Idarubicin 10 mg/m2 by vein on day 1-3 + Cytarabine 1 g/m2 by vein on day 1-5. Clofarabine: Phase I: 15 mg/m2 by vein (IV) daily for 5 days of a 28 day cycle. Phase II: Clofarabine (dose selected based on Phase I portion) by vein over approximately 1 hour daily for 5 days (days 1-5) for a 28 day cycle. Idarubicin: 10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 1-3) of a 28 day cycle. Cytarabine: 1 g/m2 by vein over approximately 2 hours daily for 5 days (days 1-5) for a 28 day cycle.		Phase II, Group 1 CIA (Clofarabine + Idarubicin + Cytarabine): Clofarabine MTD based on Phase I by vein on days 1-5; Idarubicin 10 mg/m2 by vein on days 1-3; Cytarabine 1 g/m2 by vein on days 1-5. Clofarabine: Phase I: 15 mg/m2 by vein (IV) daily for 5 days of a 28 day cycle. Phase II: Clofarabine (dose selected based on Phase I portion) by vein over approximately 1 hour daily for 5 days (days 1-5) for a 28 day cycle. Idarubicin: 10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 1-3) of a 28 day cycle. Cytarabine: 1 g/m2 by vein over approximately 2 hours daily for 5 days (days 1-5) for a 28 day cycle.		Phase II, Group 2 FLAI (Fludarabine + Idarubicin + Cytarabine): Fludarabine 30 mg/m2 by vein on days 1-5; Idarubicin 10 mg/m2 by vein on days 1-3; Cytarabine 1 g/m2 by vein on days 1-5. Idarubicin: 10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 1-3) of a 28 day cycle. Cytarabine: 1 g/m2 by vein over approximately 2 hours daily for 5 days (days 1-5) for a 28 day cycle. Fludarabine: 30 mg/m2 by vein over approximately 30 minutes daily for 5 days (days 1-5).
All Cause Mortality
	Clofarabine + Idarubicin + Cytarabine		Group 1 CIA		Group 2 FLAI
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/12 (33.3%)		8/157 (5.1%)		5/113 (4.4%)
Serious Adverse Events
	Clofarabine + Idarubicin + Cytarabine		Group 1 CIA		Group 2 FLAI
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/12 (83.3%)		126/157 (80.3%)		89/113 (78.8%)
Blood and lymphatic system disorders
Cytopenia	0/12 (0%)	0	0/157 (0%)	0	1/113 (0.9%)	1
Disseminated Intravastular Coagulation	0/12 (0%)	0	0/157 (0%)	0	1/113 (0.9%)	1
Hemorrhage	0/12 (0%)	0	6/157 (3.8%)	7	8/113 (7.1%)	8
Cardiac disorders
Cardiac Arrhythmia	0/12 (0%)	0	0/157 (0%)	0	1/113 (0.9%)	1
Chest Pain	0/12 (0%)	0	1/157 (0.6%)	1	0/113 (0%)	0
Congestive Heart Failure	0/12 (0%)		1/157 (0.6%)	1	0/113 (0%)	0
Hypertension	0/12 (0%)	0	2/157 (1.3%)	2	1/113 (0.9%)	1
Hypotension	0/12 (0%)	0	2/157 (1.3%)	2	1/113 (0.9%)	1
Left Ventricular Systolic Dysfunction	0/12 (0%)	0	1/157 (0.6%)	1	0/113 (0%)	0
Myocardial Infarction	0/12 (0%)	0	1/157 (0.6%)	1	0/113 (0%)	0
Eye disorders
Blurred Vision	0/12 (0%)	0	1/157 (0.6%)	1	0/113 (0%)	0
Gastrointestinal disorders
Allergic Reaction	0/12 (0%)	0	1/157 (0.6%)	1	1/113 (0.9%)	1
Appendicitis	0/12 (0%)	0	0/157 (0%)	0	1/113 (0.9%)	1
Cholecystitis	0/12 (0%)	0	1/157 (0.6%)	1	0/113 (0%)	0
Colitis	1/12 (8.3%)	1	0/157 (0%)	0	2/113 (1.8%)	2
Diarrhea	0/12 (0%)	0	2/157 (1.3%)	2	0/113 (0%)	0
Mucositis	0/12 (0%)	0	1/157 (0.6%)	1	1/113 (0.9%)	1
Nausea/Vomiting	1/12 (8.3%)	1	5/157 (3.2%)	7	5/113 (4.4%)	7
Pancreatitis	0/12 (0%)	0	1/157 (0.6%)	1	0/113 (0%)	0
Typhlitis	0/12 (0%)	0	1/157 (0.6%)	1	0/113 (0%)	0
General disorders
Death	4/12 (33.3%)	4	5/157 (3.2%)	5	2/113 (1.8%)	2
Fever	0/12 (0%)	0	4/157 (2.5%)	4	3/113 (2.7%)	3
Infection	7/12 (58.3%)	9	52/157 (33.1%)	80	23/113 (20.4%)	26
Pain	0/12 (0%)	0	12/157 (7.6%)	15	12/113 (10.6%)	16
Hepatobiliary disorders
Hepatorenal syndrome	0/12 (0%)	0	0/157 (0%)	0	1/113 (0.9%)	1
Infections and infestations
Neutropenic Fever	2/12 (16.7%)	2	75/157 (47.8%)	122	57/113 (50.4%)	88
Metabolism and nutrition disorders
Elevated Alanine Aminotransferase	0/12 (0%)	0	4/157 (2.5%)	4	2/113 (1.8%)	2
Elevated Amylase	0/12 (0%)	0	0/157 (0%)	0	1/113 (0.9%)	1
Elevated Amylase/Lipase	0/12 (0%)	0	0/157 (0%)	0	1/113 (0.9%)	2
Elevated Lipase	0/12 (0%)	0	0/157 (0%)	0	1/113 (0.9%)	1
Hyperbilirubinemia	1/12 (8.3%)	1	1/157 (0.6%)	1	0/113 (0%)	0
Hypocalcemia	0/12 (0%)	0	1/157 (0.6%)	1	0/113 (0%)	0
Malnutrition	0/12 (0%)	0	1/157 (0.6%)	1	0/113 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign Neoplasm	0/12 (0%)	0	1/157 (0.6%)	1	0/113 (0%)	0
Nervous system disorders
Altered Mental Status	0/12 (0%)	0	0/157 (0%)	0	1/113 (0.9%)	1
Bell's Palsy	0/12 (0%)	0	1/157 (0.6%)	1	0/113 (0%)	0
Mental Status	0/12 (0%)	0	0/157 (0%)	0	1/113 (0.9%)	1
Neuropathy	0/12 (0%)	0	1/157 (0.6%)	1	1/113 (0.9%)	1
Seizure	0/12 (0%)	0	1/157 (0.6%)	1	0/113 (0%)	0
Syncope	0/12 (0%)	0	1/157 (0.6%)	2	2/113 (1.8%)	2
Renal and urinary disorders
Acute Kidney Injury	0/12 (0%)	0	1/157 (0.6%)	1	1/113 (0.9%)	1
Cystitis	0/12 (0%)	0	0/157 (0%)	0	1/113 (0.9%)	1
Hematuria	0/12 (0%)	0	0/157 (0%)	0	1/113 (0.9%)	1
Kidney Stones	0/12 (0%)	0	1/157 (0.6%)	1	0/113 (0%)	0
Renal Failure	0/12 (0%)	0	3/157 (1.9%)	3	0/113 (0%)	0
Renal Insufficiency	0/12 (0%)	0	1/157 (0.6%)	1	0/113 (0%)	0
Respiratory, thoracic and mediastinal disorders
Hypoxia	0/12 (0%)	0	1/157 (0.6%)	1	0/113 (0%)	0
Pleural Effusion	0/12 (0%)	0	2/157 (1.3%)	2	0/113 (0%)	0
Pulmonary Embolism	0/12 (0%)	0	1/157 (0.6%)	1	0/113 (0%)	0
Respiratory Failure	0/12 (0%)	0	3/157 (1.9%)	3	3/113 (2.7%)	3
Skin and subcutaneous tissue disorders
Hand Foot Syndrome	1/12 (8.3%)	1	0/157 (0%)	0	0/113 (0%)	0
Rash	0/12 (0%)	0	2/157 (1.3%)	2	0/113 (0%)	0
Surgical and medical procedures
Drain Placement	0/12 (0%)	0	0/157 (0%)	0	1/113 (0.9%)	1
Vascular disorders
Deep Vein Thrombosis	0/12 (0%)	0	3/157 (1.9%)	3	3/113 (2.7%)	3
Other (Not Including Serious) Adverse Events
	Clofarabine + Idarubicin + Cytarabine		Group 1 CIA		Group 2 FLAI
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/12 (100%)		150/157 (95.5%)		109/113 (96.5%)
Blood and lymphatic system disorders
Hemorrhage CNS	1/12 (8.3%)	1	4/157 (2.5%)	4	2/113 (1.8%)	2
Cardiac disorders
Hypotension	1/12 (8.3%)	1	8/157 (5.1%)	9	4/113 (3.5%)	4
Gastrointestinal disorders
Colitis	1/12 (8.3%)	1	0/157 (0%)	0	4/113 (3.5%)	5
Constipation	0/12 (0%)	0	9/157 (5.7%)	9	5/113 (4.4%)	5
Hemorrhage, Gastrointestinal	0/12 (0%)	0	4/157 (2.5%)	5	7/113 (6.2%)	9
Anorexia	0/12 (0%)	0	18/157 (11.5%)	18	13/113 (11.5%)	13
Vomiting	0/12 (0%)	0	23/157 (14.6%)	27	9/113 (8%)	11
Mucositis/Stomatitis	0/12 (0%)	0	23/157 (14.6%)	24	12/113 (10.6%)	15
Diarrhea	2/12 (16.7%)	2	29/157 (18.5%)	29	20/113 (17.7%)	20
Nausea	1/12 (8.3%)	1	42/157 (26.8%)	45	27/113 (23.9%)	29
General disorders
Syndromes Other	1/12 (8.3%)	1	0/157 (0%)	0	0/113 (0%)	0
Fatigue	1/12 (8.3%)	1	29/157 (18.5%)	30	21/113 (18.6%)	22
Pain	0/12 (0%)	0	43/157 (27.4%)	53	24/113 (21.2%)	29
Infections and infestations
Opportunistic Infection	0/12 (0%)	0	6/157 (3.8%)	7	7/113 (6.2%)	7
Neutropenic Fever	8/12 (66.7%)	9	94/157 (59.9%)	140	48/113 (42.5%)	80
Infection	11/12 (91.7%)	29	70/157 (44.6%)	136	39/113 (34.5%)	66
Metabolism and nutrition disorders
Elevated Creatinine	0/12 (0%)	0	10/157 (6.4%)	10	3/113 (2.7%)	3
Elevated Aspartate Aminotransferase	2/12 (16.7%)	2	17/157 (10.8%)	17	4/113 (3.5%)	4
Elevated Alanine Aminotransferase	2/12 (16.7%)	2	40/157 (25.5%)	42	11/113 (9.7%)	11
Hyperbilirubinemia	1/12 (8.3%)	1	43/157 (27.4%)	47	14/113 (12.4%)	14
Musculoskeletal and connective tissue disorders
Muscle Weakness	1/12 (8.3%)	1	3/157 (1.9%)	3	2/113 (1.8%)	2
Nervous system disorders
Tremor	1/12 (8.3%)	1	1/157 (0.6%)	1	0/113 (0%)	0
Mental Status	1/12 (8.3%)	1	3/157 (1.9%)	3	2/113 (1.8%)	2
CNS Cerebrovascular Ischemia	1/12 (8.3%)	1	0/157 (0%)	0	0/113 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	1/12 (8.3%)	1	0/157 (0%)	0	1/113 (0.9%)	1
Dyspnea	1/12 (8.3%)	1	9/157 (5.7%)	10	1/113 (0.9%)	1
Skin and subcutaneous tissue disorders
Hand-Foot Skin Reaction	1/12 (8.3%)	1	1/157 (0.6%)	1	1/113 (0.9%)	1
Rash/Desquamation	7/12 (58.3%)	7	40/157 (25.5%)	42	11/113 (9.7%)	11

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.