Oxaliplatin, Fludarabine, and Cytarabine in Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndromes (MDS)

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00480987
• Collaborator: Sanofi (Industry)
• Enrollment: 27
• Location: 1
• Arm: 1
• Duration (Months): 37
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The goal of this clinical research study is to find the highest tolerable dose of oxaliplatin combined with fludarabine plus cytarabine that can be given to patients with Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndromes (MDS). Once the highest tolerable dose of oxaliplatin in this drug combination is found, the next goal of the study will be to learn the safety and the ability of the drug combination to control the disease.

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndromes; Acute Myeloid Leukemia; Leukemia	Drug: Oxaliplatin; Drug: Fludarabine; Drug: Cytarabine	Phase 1/Phase 2

Detailed Description

The Study Drugs:

Cytarabine is designed to insert itself into Deoxyribonucleic acid (DNA) (the genetic material of cells) and stop the DNA from repairing itself.

Fludarabine is designed to make cancer cells less able to repair damaged DNA. This may increase the likelihood of the cells dying.

Oxaliplatin is designed to "program" cells to cause death in leukemic cells.

The Phases of The Study:

This research study has 2 parts, Phase I and Phase II.

The Phase I part of the study will be used to test different dose levels in order to determine the highest tolerable dose of the study drug oxaliplatin that can be given in combination with cytarabine and fludarabine to patients with AML or high-risk MDS. Three (3) participants will be enrolled at each dose level until the highest tolerable dose is found.

The Phase II part of the study will evaluate the safety and disease-control ability of the study drug combination (the highest tolerable dose that was found) in order to treat these patients.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will be given oxaliplatin through a needle (intravenously -- through an IV) in your vein over 2 hours for 4 days (Days 1-4) in a row.

On Day 2, you will be given cytarabine through an IV in your vein by continuous infusion over 24 hours for 5 days (Days 2-6) in a row. Starting on Day 2, you will be given fludarabine through an IV in your vein over 30 minutes for 5 days (Days 2-6) in a row. In order to keep you from being dehydrated, you will also be given other IV fluids, such as saline (a salt solution), each day you receive the study drugs. If the drugs are given on an outpatient basis, a daily visit may take about 8 hours.

One (1) cycle is 6 days long. The first cycle will be given at M. D. Anderson. Each cycle will be repeated every 4-6 weeks. Depending on your response to the study drug combination, you will have up to 5 more cycles either at M. D. Anderson or on an outpatient basis with your regular physician.

Your study drug dose may be lowered if you experience severe side effects.

Study Visits:

During each treatment cycle, you will have blood drawn (about 1 teaspoon each time) at least 2-3 times a week for routine tests. You will have a bone marrow aspiration done on Day 21 of Cycle 1 and once a week thereafter, unless there is clear evidence of active disease. To collect a bone marrow aspirate, an area of the hip or chest bone is numbed with anesthetic, and a small amount of bone marrow is withdrawn through a large needle.

Length of Study:

You will remain on this study for up to 6 cycles for a total of about 6 months, unless the disease is not responding, the disease gets worse, or you experience intolerable side effects. If you are taken off this study early, your study doctor will discuss other treatment options with you.

End-of-Treatment Visit:

Once you have completed treatment on this study, you will have an end-of-treatment visit. This visit will include routine blood tests (about 1 teaspoon will be drawn each time) and a bone marrow aspirate to check the status of the disease. If your blood tests show the disease has gotten worse, no bone marrow aspirate will be needed.

Long-Term Follow-up:

After your last cycle of treatment is completed and every 3 months for as long as you are in remission, you will have blood drawn (about 2 teaspoons each) for routine testing.

This is an investigational study. Cytarabine is Food and Drug Administration (FDA) approved and commercially available for the treatment of AML and other blood cancers. Fludarabine is FDA approved and commercially available for the treatment of chronic lymphocytic leukemia (CLL). Oxaliplatin is FDA approved and commercially available for the treatment of advanced colorectal cancer and colon cancer. Their use in combination is investigational in this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 27 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I-II Study of Oxaliplatin, Fludarabine, and Cytarabine in Patients With Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes at First Relapse With Complete Remission Duration < 1 Year
• Study Start Date: Jul 1, 2007
• Actual Primary Completion Date: Aug 1, 2010
• Actual Study Completion Date: Aug 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Oxaliplatin + Cytarabine + Fludarabine Oxaliplatin 30 mg/m^2 intravenous (IV) days 1-4, Cytarabine 500 mg/m^2 by IV continuous infusion days 2-6, Fludarabine 30 mg/m^2 IV days 2-6	Drug: Oxaliplatin; 30 mg/m^2 IV days 1-4; Other Names: Eloxatin® ; Drug: Fludarabine; 30 mg/m^2 IV days 2-6; Other Names: Fludara® Fludarabine Phosphate ; Drug: Cytarabine; 500 mg/m^2 by IV continuous infusion days 2-6; Other Names: Ara-C

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Objective Response [After 2 months]

   Objective response: Complete Response/Remission (CR) defined as a bone marrow with 5% or fewer blasts and peripheral blood count with an absolute neutrophil count of 10^9/Liters or more and platelet count of 100*10^9/Liters or more; Complete Response with Platelets/remission without platelet recovery (CRp) defined as a complete response except for a platelet less than 100*10^9/Liters and transfusion independent; and Partial Response/Remission defined as peripheral blood count recovery as for CR with decrease in marrow blasts >/= 50% and not more than 6-25% abnormal cells in the marrow.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically or cytologically confirmed relapsed or refractory acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome.

• Performance status 0-2 (Zubrod scale).

• Serum creatinine equal or less than 1.3 mg/dL or creatinine clearance > 40 mL/min.

• Bilirubin </= 2 mg/dL; serum glutamic oxaloacetic transaminase (SGOT) or Serum glutamic pyruvic transaminase (SGPT) </= 3 times the Upper Limit of Normal (ULN) for the reference lab unless due to leukemia or congenital hemolytic disorder (for bilirubin).

• Written informed consent.

Exclusion Criteria:

• No untreated or uncontrolled life-threatening infection.

• No oxaliplatin, fludarabine, or cytarabine intolerance.

• No pregnancy or lactation. Female patients of childbearing potential (including those < 1 year post-menopausal) and male patients must agree to use contraception.

• No chemotherapy or radiation therapy within 4 weeks of study entry. Hydroxyurea is allowed prior to starting therapy in the setting of rapidly proliferating disease.

• No other medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent or cooperate and participate in the study or to interfere with the interpretation of the results.

Contacts and Locations

Locations

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

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• Sanofi

Investigators

• Principal Investigator: Gautam Borthakur, M.D., M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• UT MD Anderson Cancer Center website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT00480987
• Other Study ID Numbers: 2006-1089
• First Posted: Jun 1, 2007
• Last Update Posted: Aug 7, 2012
• Last Verified: Aug 1, 2012

• Keywords provided by M.D. Anderson Cancer Center: High-Risk Myelodysplastic Syndromes; Acute Myeloid Leukemia; Leukemia; Oxaliplatin; Fludarabine; Cytarabine; AML; MDS
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Myelodysplastic Syndromes; Syndrome; Vidarabine; Cytarabine; Oxaliplatin; Fludarabine; Fludarabine phosphate

Study Results

Participant Flow

Recruitment Details	Recruitment Period 1/15/08 - 11/3/09; all patients were registered at The University of Texas M.D. Anderson Cancer Center.
Pre-assignment Detail	There were 27 participants registered and all were included in the analysis. The trial terminated early.

Arm/Group Title	Oxaliplatin + Cytarabine + Fludarabine
Arm/Group Description	Oxaliplatin 30 mg/m^2 intravenous (IV) days 1-4, Cytarabine 500 mg/m^2 by IV continuous infusion days 2-6, Fludarabine 30 mg/m^2 IV days 2-6
Period Title: Overall Study
STARTED	27
COMPLETED	27
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Oxaliplatin + Cytarabine + Fludarabine
Arm/Group Description	Oxaliplatin 30 mg/m^2 intravenous (IV) days 1-4, Cytarabine 500 mg/m^2 by IV continuous infusion days 2-6, Fludarabine 30 mg/m^2 IV days 2-6
Overall Participants	27
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	58
Sex: Female, Male (Count of Participants)
Female	15 55.6%
Male	12 44.4%
Region of Enrollment (participants) [Number]
United States	27 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Objective Response
Description	Objective response: Complete Response/Remission (CR) defined as a bone marrow with 5% or fewer blasts and peripheral blood count with an absolute neutrophil count of 10^9/Liters or more and platelet count of 100*10^9/Liters or more; Complete Response with Platelets/remission without platelet recovery (CRp) defined as a complete response except for a platelet less than 100*10^9/Liters and transfusion independent; and Partial Response/Remission defined as peripheral blood count recovery as for CR with decrease in marrow blasts >/= 50% and not more than 6-25% abnormal cells in the marrow.
Time Frame	After 2 months

Outcome Measure Data

Analysis Population Description

Analysis was per protocol. All participants treated were analyzed.

Arm/Group Title	Oxaliplatin + Cytarabine + Fludarabine
Arm/Group Description	Oxaliplatin 30 mg/m^2 intravenous (IV) days 1-4, Cytarabine 500 mg/m^2 by IV continuous infusion days 2-6, Fludarabine 30 mg/m^2 IV days 2-6
Measure Participants	27
Complete response	3 11.1%
Complete response with platelets	2 7.4%
Partial response	0 0%

Adverse Events

Time Frame	2 years
Arm/Group Title	Oxaliplatin + Cytarabine + Fludarabine
Arm/Group Description	Oxaliplatin 30 mg/m^2 intravenous (IV) days 1-4, Cytarabine 500 mg/m^2 by IV continuous infusion days 2-6, Fludarabine 30 mg/m^2 IV days 2-6
All Cause Mortality
	Oxaliplatin + Cytarabine + Fludarabine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Oxaliplatin + Cytarabine + Fludarabine
	Affected / at Risk (%)	# Events
Total	5/27 (18.5%)
General disorders
Death	5/27 (18.5%)	5
Infections and infestations
Pneumonia	2/27 (7.4%)	2
Other (Not Including Serious) Adverse Events
	Oxaliplatin + Cytarabine + Fludarabine
	Affected / at Risk (%)	# Events
Total	10/27 (37%)
Gastrointestinal disorders
Diarrhea	4/27 (14.8%)	4
Hepatobiliary disorders
Hyperbilirubinemia	3/27 (11.1%)	3
Elevated aspartate aminotransferase	3/27 (11.1%)	3

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.