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

Sponsor
M.D. Anderson Cancer Center (Other)
Overall Status
Completed
CT.gov ID
NCT01019317
Collaborator
(none)
151
Enrollment
1
Location
1
Arm
34
Duration (Months)
4.4
Patients Per Site Per Month

Study Details

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 DiseaseIntervention/TreatmentPhase
Phase 2

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

Study Type:
Interventional
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 :
Nov 1, 2009
Actual Primary Completion Date :
Sep 1, 2012
Actual Study Completion Date :
Sep 1, 2012

Arms and Interventions

ArmIntervention/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

    1. Participants With a Complete Response [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

    Criteria

    Ages Eligible for Study:
    12 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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):

    1. 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.
    1. 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).

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1UT MD Anderson Cancer CenterHoustonTexasUnited States77030

    Sponsors and Collaborators

    • M.D. Anderson Cancer Center

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    M.D. Anderson Cancer Center
    ClinicalTrials.gov Identifier:
    NCT01019317
    Other Study ID Numbers:
    • 2009-0781
    First Posted:
    Nov 25, 2009
    Last Update Posted:
    Mar 15, 2016
    Last Verified:
    Oct 1, 2013

    Study Results

    Participant Flow

    Recruitment DetailsRecruitment Period: 11/23/2009 through 10/25/2010. All participants recruited at UT MD Anderson Cancer Center.
    Pre-assignment DetailOf the 151 participants enrolled, four (4) participants were excluded from the trial before treatment.
    Arm/Group TitleCytarabine + Fludarabine
    Arm/Group DescriptionFludarabine 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.
    Period Title: Overall Study
    STARTED151
    COMPLETED147
    NOT COMPLETED4

    Baseline Characteristics

    Arm/Group TitleCytarabine + Fludarabine
    Arm/Group DescriptionFludarabine 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.
    Overall Participants151
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    63
    Sex: Female, Male (Count of Participants)
    Female
    63
    41.7%
    Male
    88
    58.3%
    Region of Enrollment (participants) [Number]
    United States
    151
    100%

    Outcome Measures

    1. Primary Outcome
    TitleParticipants With a Complete Response
    DescriptionComplete 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.
    Time FrameMinimally 6 weeks (Cycle 1) up to 1 year (7 cycles)

    Outcome Measure Data

    Analysis Population Description
    Of participants enrolled, 147 participants received treatment and were evaluable.
    Arm/Group TitleCytarabine + Fludarabine
    Arm/Group DescriptionFludarabine 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.
    Measure Participants147
    Number [Participants]
    34
    22.5%

    Adverse Events

    Time FrameTwo years, ten months.
    Adverse Event Reporting Description Of the 151 participants registered, four did not recieve treatment and were excluded from adverse event reporting.
    Arm/Group TitleCytarabine + Fludarabine
    Arm/Group DescriptionFludarabine 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.
    All Cause Mortality
    Cytarabine + Fludarabine
    Affected / at Risk (%)# Events
    Total/ (NaN)
    Serious Adverse Events
    Cytarabine + Fludarabine
    Affected / at Risk (%)# Events
    Total0/147 (0%)
    Other (Not Including Serious) Adverse Events
    Cytarabine + Fludarabine
    Affected / at Risk (%)# Events
    Total100/147 (68%)
    Gastrointestinal disorders
    Nausea34/147 (23.1%) 34
    Vomiting12/147 (8.2%) 12
    Diarrhea20/147 (13.6%) 20
    Mucositis18/147 (12.2%) 18
    Hepatobiliary disorders
    Elevated Liver Function16/147 (10.9%) 16
    Infections and infestations
    Infection78/147 (53.1%) 78
    Skin and subcutaneous tissue disorders
    Rash15/147 (10.2%) 15

    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.

    Results Point of Contact

    Name/TitleElias Joseph Jabbour MD/Assistant Professor
    OrganizationUniversity of Texas (UT) MD Anderson Cancer Center
    Phone713-792-4764
    Emaileharriso@mdanderson.org
    Responsible Party:
    M.D. Anderson Cancer Center
    ClinicalTrials.gov Identifier:
    NCT01019317
    Other Study ID Numbers:
    • 2009-0781
    First Posted:
    Nov 25, 2009
    Last Update Posted:
    Mar 15, 2016
    Last Verified:
    Oct 1, 2013