Fludarabine and Cytarabine in Acute Myelogenous Leukemia (AML) and High-Risk Myelodysplastic Syndrome (MDS)

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ClinicalTrials.gov Identifier: NCT01019317

Recruitment Status : Completed

First Posted : November 25, 2009

Results First Posted : December 3, 2013

Last Update Posted : March 15, 2016

Sponsor:

Information provided by (Responsible Party):

M.D. Anderson Cancer Center

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Leukemia AML MDS CML	Drug: Cytarabine Drug: Fludarabine	Phase 2

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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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	151 participants
Allocation:	N/A
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Phase II Study of Twice Daily Cytarabine and Fludarabine in Acute Myelogenous Leukemia and High-Risk Myelodysplastic Syndrome
Study Start Date :	November 2009
Actual Primary Completion Date :	September 2012
Actual Study Completion Date :	September 2012

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Familial acute myeloid leukemia with mutated CEBPA Cytogenetically normal acute myeloid leukemia Core binding factor acute myeloid leukemia

MedlinePlus related topics: Acute Myeloid Leukemia Leukemia Myelodysplastic Syndromes

Drug Information available for: Cytarabine Fludarabine Fludarabine phosphate

Genetic and Rare Diseases Information Center resources: Myeloid Leukemia Acute Myeloid Leukemia Acute Non Lymphoblastic Leukemia Myelodysplastic Syndromes Chronic Myeloid Leukemia

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cytarabine + Fludarabine Fludarabine 15 mg/m^2 intravenous (IV) every 12 hours for 5 days; Cytarabine 0.5 grams/m^2 IV over 2 hours every 12 hours for 5 days.	Drug: Cytarabine 0.5 grams/m^2 over 2 hours(+/- 15 minutes) IV every 12 (+/-2) hours for 5 days (4 days in patients > 65 years and 3 days in patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) > 3). Other Names: Ara-C Cytosar DepCyt Cytosine arabinosine hydrochloride Drug: Fludarabine 15 mg/m^2 to be given IV over 15-30 minutes every 12 (+/- 2) hours for 5 days. (4 days in patients > 65 years and 3 days in patients with PS > 3). Other Names: Fludara Fludarabine Phosphate

Arm

Intervention/treatment

Experimental: Cytarabine + Fludarabine

Fludarabine 15 mg/m^2 intravenous (IV) every 12 hours for 5 days; Cytarabine 0.5 grams/m^2 IV over 2 hours every 12 hours for 5 days.

Drug: Cytarabine

0.5 grams/m^2 over 2 hours(+/- 15 minutes) IV every 12 (+/-2) hours for 5 days (4 days in patients > 65 years and 3 days in patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) > 3).

Other Names:

Ara-C
Cytosar
DepCyt
Cytosine arabinosine hydrochloride

Drug: Fludarabine

15 mg/m^2 to be given IV over 15-30 minutes every 12 (+/- 2) hours for 5 days. (4 days in patients > 65 years and 3 days in patients with PS > 3).

Other Names:

Fludara
Fludarabine Phosphate

Outcome Measures

Primary Outcome Measures :

Participants With a Complete Response [ Time Frame: Minimally 6 weeks (Cycle 1) up to 1 year (7 cycles) ]
Complete Response (CR) was defined as: Neutrophil count ≥ 1.0 ×109/L, Platelet count ≥ 100 ×109/L, Bone marrow aspirate ≤5% blasts and No extramedullary leukemia. Response evaluation following Induction Therapy (Cycle 1) and every 2-3 cycles during Consolidation Therapy (Cycles 2 - 7) where Cycle is 4-6 weeks.

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:	12 Years and older (Child, Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Sign an Internal Review Board (IRB)-approved informed consent document.
Age >/= 12 years.
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.
Eastern Cooperative Oncology Group (ECOG) performance status of </= 3 at study entry.
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.
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:

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01019317

Locations

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United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030

Sponsors and Collaborators

M.D. Anderson Cancer Center

Investigators

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Study Chair:	Elias Jabbour, MD	UT MD Anderson Cancer Center

More Information

Additional Information:

UT MD Anderson Cancer Center website This link exits the ClinicalTrials.gov site

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Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT01019317
Other Study ID Numbers:	2009-0781
First Posted:	November 25, 2009 Key Record Dates
Results First Posted:	December 3, 2013
Last Update Posted:	March 15, 2016
Last Verified:	October 2013

Keywords provided by M.D. Anderson Cancer Center:


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

Additional relevant MeSH terms:

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Leukemia Preleukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Myelodysplastic Syndromes Neoplasms by Histologic Type Neoplasms Bone Marrow Diseases Hematologic Diseases Precancerous Conditions Vidarabine Cytarabine	Fludarabine Fludarabine phosphate Antineoplastic Agents Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antiviral Agents Anti-Infective Agents

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