Clinical trial NCT00480987: Oxaliplatin, Fludarabine, and Cytarabine in Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndromes (MDS)
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Myelodysplastic Syndromes
Acute Myeloid Leukemia
Leukemia
Keywords: High-Risk Myelodysplastic Syndromes
Acute Myeloid Leukemia
Leukemia
Oxaliplatin
Fludarabine
Cytarabine
AML
MDS
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: Sanofi
First posted: 2007-06-01
Enrollment: 27
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Objective Response
timeFrame: After 2 months
Secondary outcomes:
Other outcomes:
Locations:
city: Houston
country: United States
facility: UT MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Gautam Borthakur, M.D.
role: PRINCIPAL_INVESTIGATOR
References: