Clinical trial NCT01019317: Fludarabine and Cytarabine in Acute Myelogenous Leukemia (AML) and High-Risk Myelodysplastic Syndrome (MDS)
Official title: A Phase II Study of Twice Daily Cytarabine and Fludarabine in Acute Myelogenous Leukemia and High-Risk Myelodysplastic Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
AML
MDS
CML
Keywords: Acute Myelogenous Leukemia
High-Risk Myelodysplastic Syndrome
Chronic myeloid leukemia
CML
Blast crisis
Cytarabine
Ara-C
Cytosar
DepoCyt
Cytosine arabinosine hydrochloride
Arabinosine Hydrochloride
Fludarabine
Fludarabine Phosphate
Fludara
Gemtuzumab Ozogamicin
Mylotarg
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
First posted: 2009-11-25
Enrollment: 151
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The goal of this clinical research study is to learn if the combination of fludarabine and cytarabine can help to control Acute Myelogenous Leukemia (AML), High-Risk Myelodysplastic Syndrome (MDS) or Chronic Myeloid Leukemia (CML) in myeloid blast crisis. The safety of this drug combination will also be studied.

Detailed description: The Study Drugs Fludarabine is designed to make cancer cells less able to repair damaged DNA (the genetic material of cells). This may increase the likelihood of the cells dying.

Cytarabine is designed to insert itself into DNA and stop the DNA from repairing itself.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will receive fludarabine and cytarabine.

During each cycle (about 4-6 weeks), you will receive the study drugs for up to 5 days and you will be watched by the study staff for about 1 month.

Induction (Cycle 1):

For 3, 4, or 5 days during Days 1-5 of Cycle 1, you will receive fludarabine by vein over 15-30 minutes 2 times a day (about every 12 hours).

For 3, 4, or 5 days during Days 1-5 of Cycle 1, you will receive cytarabine by vein over about 2 hours 2 times a day (about every 12 hours).

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.

Consolidation (Cycles 2-7):

For 3 or 4 days during Days 1-4 of Cycles 2-7, you will receive fludarabine by vein over 15-30 minutes 2 times a day (about every 12 hours).

For 3 or 4 days during Days 1-4 of Cycles 2-7, you will receive cytarabine by vein over about 2 hours 2 times a day (about every 12 hours).

Study Visits:

At each study visit, you will be asked about any side effects you may be having and about any other drugs you may be taking.

During Induction Therapy (Cycle 1):

* Blood (about 2 tablespoons) will be drawn for routine tests every 3-7 days.
* About Day 28, you may have a bone marrow aspirate to check the status of the disease.

During Consolidation Therapy (Cycles 2-7):

* Blood (about 2 tablespoons) will be drawn for routine tests every 1-2 weeks.
* You will have a bone marrow aspirate every 2-3 cycles to check the status of the disease.

Length of Study:

You will be able to receive the study drugs for up to about 8 months. You will be taken off study treatment if you have intolerable side effects, if the disease gets worse, or if the study doctor thinks it is in your best interest.

Long-Term Follow-Up:

Every 3 months for 2 years after you are off study treatment, you will be called and asked how you are feeling, about any side effects you may be having, and about another other drugs you may be taking.

Supportive Care:

Please talk with your doctor about drugs that you can or cannot take while you are on study.

This is an investigational study. Cytarabine is FDA approved and commercially available as a frontline (first) treatment for AML. Fludarabine is FDA approved and commercially available for the treatment of CLL.

The combination of these 2 drugs to treat AML, MDS, or CML in myeloid blast crisis is investigational.

Up to 150 patients will take part in this study. All will be enrolled at M. D. Anderson.

Eligibility criteria: Inclusion Criteria:

1. Sign an Internal Review Board (IRB)-approved informed consent document.
2. Age \>/= 12 years.
3. Diagnosis of AML \[other than acute promyelocytic leukemia (APL)\] with refractory/relapsed disease. Patients with newly diagnosed AML will be eligible if not a candidate for intensive chemotherapy. Patients with high-risk (intermediate-2 or high by IPSS or \>/=10% blasts) MDS will also be eligible. Patients with chronic myeloid leukemia (CML) in blast crisis will be eligible as well.
4. Eastern Cooperative Oncology Group (ECOG) performance status of \</= 3 at study entry.
5. Organ function as defined below (unless due to leukemia):

   i. Serum creatinine \</= 3 mg/dL; ii. Total bilirubin \</= 3 mg/dL; iii. Alanine aminotransferase (ALT)(Serum Glutamic Pyruvate Transaminase (SGPT)) \</= 5 times upper limit of normal (ULN) or \</= 10 times ULN if related to disease.
6. Women of childbearing potential (WCBP) must have a negative serum or urine pregnancy test within 7 days . Men must agree not to father a child and agree to use a condom if his partner is of child bearing potential.

Exclusion Criteria:

1. Pregnant or breastfeeding females.
2. Diagnosis of acute promyelocytic leukemia (M3).

Primary outcomes:
measure: Participants With a Complete Response
timeFrame: Minimally 6 weeks (Cycle 1) up to 1 year (7 cycles)
Secondary outcomes:
Other outcomes:
Locations:
city: Houston
country: United States
facility: UT MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: UT MD Anderson Cancer Center
name: Elias Jabbour, MD
role: STUDY_CHAIR
References: