Fludarabine, Cytarabine, Filgrastim and Idarubicin in Core Binding Factor (CBF) Leukemias

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2016 by M.D. Anderson Cancer Center
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00801489
First received: December 2, 2008
Last updated: July 19, 2016
Last verified: July 2016
  Purpose
The goal of this clinical research study is to learn if idarubicin can be added to the combination of fludarabine, cytarabine, and Neupogen (Filgrastim) without increasing the risk of side effects. This study will also look at whether the addition of idarubicin will increase the long-term chances of patients remaining disease free.

Condition Intervention Phase
Acute Myelogenous Leukemia
Drug: Fludarabine
Drug: Cytarabine
Drug: G-CSF (Filgrastim, Neupogen)
Drug: Idarubicin
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Fludarabine, Cytarabine, Filgrastim and Idarubicin in Newly Diagnosed Core Binding Factor Associated Acute Myelogenous Leukemia

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Complete Response (CR) Rate and Toxicity Rate [ Time Frame: Weekly blood tests, bone marrow aspirate Days 18-24 and at 4 + 7 months, blood tests every 2-3 months for 2 years ] [ Designated as safety issue: Yes ]

    Response criteria recommended by the NCI and MDS International Working Group. Complete Response (CR): Peripheral blood counts, No circulating blasts, Neutrophil count ≥ 1.0 X 109/L, Platelet count ≥ 100 X 109/L, Bone marrow aspirate and biopsy, ≤5% blasts, No detectable auer rods, No extramedullary leukemia

    CRp: Response as in CR but platelets <100 X 109/L

    Partial response (PR): Peripheral blood counts, No circulating blasts, Neutrophil count ≥ 1.0 X 109/L, Platelet count ≥ 100 X 109/L, ≥ 50% reduction in bone marrow blasts over baseline



Secondary Outcome Measures:
  • Event Free Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Event free survival at 2 years defined as death and relapses.


Estimated Enrollment: 180
Study Start Date: April 2007
Estimated Primary Completion Date: April 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Remission Induction Group
Fludarabine by vein on Days 1, 2, 3, 4, and 5. Cytarabine by vein on Days 1, 2, 3, 4, and 5 infusion starting 3.5 hours after the completion of Fludarabine. Idarubicin by vein given immediately after Fludarabine administration on Days 3 and 4. Filgrastim starting Day -1 till recovery of absolute neutrophil count (ANC) to 1.0 X 10^9/L or above. (Filgrastim started after WBC count is < 5 X 10^9/L for patients with presenting WBC count > 10 X 10^9/L).
Drug: Fludarabine
30 mg/m^2 intravenously days 1, 2, 3, 4, and 5 (infusion time approximately 30 minutes). Post-Remission Therapy will consist of 3 days rather than 5 days.
Other Name: Fludara®
Drug: Cytarabine
2 g/m^2 intravenously over 4 hours daily days 1, 2, 3, 4, and 5; each infusion begins 3.5 hours after completion of that day's fludarabine infusion - Post-Remission Therapy will consist of 3 days rather than 5 days.
Other Names:
  • Cytosar-U
  • Ara-C
Drug: G-CSF (Filgrastim, Neupogen)
5 mcg/kg body weight (rounded off to the nearest number) starting day-1 till recovery of absolute neutrophil count (ANC) to 1.0 x 109/L or above. (G-CSF will be started on day 2 for patients with presenting WBC count > 10 x 109/L. Post-Remission Therapy will consist of 4 days rather than 5 days.
Other Names:
  • Neupogen
  • Granulocyte Colony-Stimulating Factor
  • G-CSF
Drug: Idarubicin
6 mg/m2 by vein over 30 minutes to be given immediately after fludarabine administration on Days 3 and 4. Idarubicin will be administered as in induction cycle, in one post-remission cycle (from cycle 3-6). Idarubicin will be given immediately after fludarabine administration on Days 2 and 3.
Other Name: Idamycin
Experimental: Post-Remission Therapy Group
Fludarabine, Cytarabine, and Filgrastim as during induction except that Fludarabine and Cytarabine given for 3, rather than 5 days. Idarubicin administered as in induction cycle, in one post-remission cycle (from cycle 3-6). Idarubicin given immediately after Fludarabine administration on Days 2 and 3. Filgrastim given on Day -1 of each post-remission cycle irrespective of WBC count.
Drug: Fludarabine
30 mg/m^2 intravenously days 1, 2, 3, 4, and 5 (infusion time approximately 30 minutes). Post-Remission Therapy will consist of 3 days rather than 5 days.
Other Name: Fludara®
Drug: Cytarabine
2 g/m^2 intravenously over 4 hours daily days 1, 2, 3, 4, and 5; each infusion begins 3.5 hours after completion of that day's fludarabine infusion - Post-Remission Therapy will consist of 3 days rather than 5 days.
Other Names:
  • Cytosar-U
  • Ara-C
Drug: G-CSF (Filgrastim, Neupogen)
5 mcg/kg body weight (rounded off to the nearest number) starting day-1 till recovery of absolute neutrophil count (ANC) to 1.0 x 109/L or above. (G-CSF will be started on day 2 for patients with presenting WBC count > 10 x 109/L. Post-Remission Therapy will consist of 4 days rather than 5 days.
Other Names:
  • Neupogen
  • Granulocyte Colony-Stimulating Factor
  • G-CSF
Drug: Idarubicin
6 mg/m2 by vein over 30 minutes to be given immediately after fludarabine administration on Days 3 and 4. Idarubicin will be administered as in induction cycle, in one post-remission cycle (from cycle 3-6). Idarubicin will be given immediately after fludarabine administration on Days 2 and 3.
Other Name: Idamycin

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must have untreated AML, or high-risk MDS [refractory anemia with excess blasts, (RAEB), or RAEB "in transformation" (RAEB-t)] characterized by t(8;21), inv(16), or t(16;16).The presence of additional abnormalities is irrelevant.
  2. Age equal to or greater than 18 years (the safety of GO in patients <18 years is not determined and advantage of fludarabine, cytarabine, idarubicin-based regimen in CBF leukemias in children is not demonstrated).
  3. Patients must provide written consent.
  4. Because of the high possibility of CR in CBF leukemias, participants will not be excluded based on performance status.For patients with Eastern Co-operative Oncology Group (ECOG) performance status >/= to 3 the dosing schedule will be discussed with study chairman.
  5. Patients with organ dysfunction will not be excluded from the study. For patients with evidence of organ dysfunction (creatinine >/= 1.5, cardiac ejection fraction </= 50%, total bilirubin >/=2 and AST/ALT >/= 3 times ULN, dose adjustments/omissions will be made.
  6. Up to one cycle of prior induction therapy will be permitted to include patients in whom presence of "good-risk" cytogenetics was initially missed. If the patient is in remission from induction therapy, he/she will receive post-remission therapy. If the patient is not in remission then he/she will receive induction therapy.
  7. Patients of child bearing potential should practice effective methods of contraception.

Exclusion Criteria:

1) Pregnant and lactating females will be excluded since the safety of GO or FLAG + Ida in pregnancy and lactation is unknown.

  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00801489

Contacts
Contact: Gautam Borthakur, MD 713-563-1586

Locations
United States, Texas
The University of Texas M.D. Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Gautam Borthakur, MD    713-563-1586      
Principal Investigator: Gautam Borthakur, MD         
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Gautam Borthakur, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00801489     History of Changes
Other Study ID Numbers: 2007-0147  NCI-2012-01659 
Study First Received: December 2, 2008
Last Updated: July 19, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Leukemia
Acute Myelogenous Leukemia
AML

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Fludarabine
Fludarabine phosphate
Cytarabine
Idarubicin
Vidarabine
Lenograstim
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antiviral Agents
Anti-Infective Agents
Adjuvants, Immunologic
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 29, 2016