Back to resultsFludarabine, Cytarabine, Topotecan in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia (FLAT)
Primary Purpose
Acute Myeloid Leukemia
Status
Completed
Phase
Phase 4
Locations
Spain
Study Type
Interventional
Intervention
Topotecan
Fludarabine
Cytarabine
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring Acute Myeloid Leukemia, Multi Drug Resistance
Eligibility Criteria
Inclusion Criteria:
Subjects of 18 years of age or major, with diagnosis of primary or secondary AML, confirmed cytologically, that fulfill one of the following conditions:
- Do not reach a CR after the conventional treatment.
- Relapse in the first 12 months after a CR. During remission, patients can have be treated by a transplant. The relapse is defined as the presence of blasts in peripheric blood or the presence of >5 % of blasts in MO.
- Not participation in a clinical trial.
- ECOG < o = 2
- Considered suitable patients for an intensive chemotherapy
- Informed consent
Exclusion Criteria:
- Pelvic or spinal radiotherapy in 4 weeks before the incorporation in the protocol.
- Acute promyelocytic leukaemia
- First line chemotherapy for AML which has contained fludarabine or topotecan.
- Active or chronic hepatitis or hepatic cirrhosis.
- Positivity known to the virus of the human immunodeficiency (HIV)
- Pregnant or breastfeeding patients.
Patients with deterioration of the functions hepatic or renal, defined for the following values base them of laboratory:
- AST or ALT >2,5 times the top limit of the normality of the center (LSNC)
- Alkaline phosphatase >2,5 times the LSNC
- Total bilirubin value >2 times the LSNC
- Creatinine value >2 times the LSNC after a suitable hydration
- Precedents of intervention of major surgery in 2 weeks before the incorporation in the protocol.
- Patients with disease serious or not controlled (for example not controlled diabetes, infection, hypertension, etc.).
- Patients who have received other cytotoxic drugs (except hydroxyurea to reduce the leucocytosis) as treatment of the current relapse or of the resistance, in 4 weeks before the protocol.
- Patients with hypersensitivity known to someone of the drugs of the protocol.
- Patients treated previously with growth factors with purposes of sensibilization.
- Patients with psychological, intellectual or sensitive dysfunction that can reduce his capacity of comprehension and fulfillment of the protocol.
- Patients treated before with FLAT.
Sites / Locations
- Hospital Juan Canalejo
- Hospital Ntra. Sra. de Sonsoles
- Hospital germans Trias i Pujol
- Centro Médico Teknon
- Hospital Sant Pau
- Hospital Vall d'Hebron
- Hospital General Yagüe
- Hospital de Jerez
- Complejo hospitalario Xeral-Calde
- Hospital Clínico Universitario San Carlos
- Hospital Ramón y Cajal
- Hospital Virgen de la Victoria
- Hosptal Joan XXIII
- Hospital Verge de la Cinta
- Hospital Rio Hortega
- Hospital Clinico Lozano Blesa
Outcomes
Primary Outcome Measures
To treat with the combination FLAT patients with acute myeloid leukaemia that they present a primary resistance
•To treat with the combination FLAT a relapse in the first 12 months after reach the first CR with standard treatment
To treat with combination FLAT patients can't receive the standard treatment due any cause
Secondary Outcome Measures
Improve the interval free survival and global survival
To avoid the toxicities produced by other chemotherapy in this type of patients
To determine the existing association between the response to the treatment with FLAT and the expression of Multi Drug Resistance (MDR) in the acute myeloid leukaemia
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00488709
Brief Title
Fludarabine, Cytarabine, Topotecan in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia
Acronym
FLAT
Official Title
FLAT: Fludarabine, Cytarabine and Topotecan in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia
Study Type
Interventional
2. Study Status
Record Verification Date
November 2008
Overall Recruitment Status
Completed
Study Start Date
May 2003 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
April 2007 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
PETHEMA Foundation
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The study is designed with drugs used frequently in the treatment of AML, but with a new combination less toxic,and effective in AML multidrug resistant.
Justification:
The AML patients with primary resistance or relapsed in the first 12 months after CR, have second line chemotherapy low response rate .
These patients with AML with primary resistance or relapse, that reach remission after a rescue treatment, have an interval free survival and a global survival very short
Probably the resistance to the treatments is in relation to different forms expression of the MDR.
Complete remission is considered valid evaluation, because every patient who should obtain a CR can be considered to be eligible for a possible curative treatment: Ara-C administration to high doses or the TPH treatment
Detailed Description
It is a protocol opened, multicentric, led to end to increase a) the rate of complete responses, b) the duration of the response, c) the free survival of disease and d) the global survival.
The included subjects will be patients with primary or secondary AML that they have not achieved the CR after the standard treatment with an anthracycline or derivative associated with Ara-C or have relapsed in the first 12 months after having achieved the RC. Also patients with AML that, for any reason, they could not receive the standard treatment with anthracycline and Ara-C, will be included
Cycle of induction. The patients will be treated by FLAT according to the following scheme:
FLUDARABINE, 30 mg/m2 i.v. (In 1 hour) on the 1st to 4.
CITARABINE, 2 g/m2 i.v. (In 4 hours), four hours after finishing the fludarabine, on the 1st to 4.
TOPOTECAN, 1,5 mg/m2 i.v. (In 4 hours), four hours after finishing the cytarabine, on the 1st to 4.
When the patient starts recovering the hematological counts, and providing that has not blasts in the peripheral blood (SP), he will become a medullar revision (MO):
If MO presents severe hypocellularity without blasts,no therapeutic measurement will take and there will repeat revisions weekly and MDR's study up to the CR or the blasts appearance.
If in MO persist blasts (>5 %) but have diminished less than 50 % of the initial number, the induction will be continued by the FLAT's second shift.
If in MO persists more than 50 % of blasts of the initial number, the patient goes out of the protocol and it will be treated as an agreement by the criterion of the center.
The patients who have managed to enter CR will receive a cycle of consolidation as soon as possible and always within 2 months from the day in which they received first FLAT's dose. The cycle of consolidation consists of another FLAT's scheme to the same doses.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia
Keywords
Acute Myeloid Leukemia, Multi Drug Resistance
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
47 (Actual)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
Topotecan
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Type
Drug
Intervention Name(s)
Cytarabine
Primary Outcome Measure Information:
Title
To treat with the combination FLAT patients with acute myeloid leukaemia that they present a primary resistance
Time Frame
one month
Title
•To treat with the combination FLAT a relapse in the first 12 months after reach the first CR with standard treatment
Time Frame
one month
Title
To treat with combination FLAT patients can't receive the standard treatment due any cause
Time Frame
one month
Secondary Outcome Measure Information:
Title
Improve the interval free survival and global survival
Time Frame
one year
Title
To avoid the toxicities produced by other chemotherapy in this type of patients
Time Frame
4 months
Title
To determine the existing association between the response to the treatment with FLAT and the expression of Multi Drug Resistance (MDR) in the acute myeloid leukaemia
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subjects of 18 years of age or major, with diagnosis of primary or secondary AML, confirmed cytologically, that fulfill one of the following conditions:
Do not reach a CR after the conventional treatment.
Relapse in the first 12 months after a CR. During remission, patients can have be treated by a transplant. The relapse is defined as the presence of blasts in peripheric blood or the presence of >5 % of blasts in MO.
Not participation in a clinical trial.
ECOG < o = 2
Considered suitable patients for an intensive chemotherapy
Informed consent
Exclusion Criteria:
Pelvic or spinal radiotherapy in 4 weeks before the incorporation in the protocol.
Acute promyelocytic leukaemia
First line chemotherapy for AML which has contained fludarabine or topotecan.
Active or chronic hepatitis or hepatic cirrhosis.
Positivity known to the virus of the human immunodeficiency (HIV)
Pregnant or breastfeeding patients.
Patients with deterioration of the functions hepatic or renal, defined for the following values base them of laboratory:
AST or ALT >2,5 times the top limit of the normality of the center (LSNC)
Alkaline phosphatase >2,5 times the LSNC
Total bilirubin value >2 times the LSNC
Creatinine value >2 times the LSNC after a suitable hydration
Precedents of intervention of major surgery in 2 weeks before the incorporation in the protocol.
Patients with disease serious or not controlled (for example not controlled diabetes, infection, hypertension, etc.).
Patients who have received other cytotoxic drugs (except hydroxyurea to reduce the leucocytosis) as treatment of the current relapse or of the resistance, in 4 weeks before the protocol.
Patients with hypersensitivity known to someone of the drugs of the protocol.
Patients treated previously with growth factors with purposes of sensibilization.
Patients with psychological, intellectual or sensitive dysfunction that can reduce his capacity of comprehension and fulfillment of the protocol.
Patients treated before with FLAT.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bueno Javier, Dr
Organizational Affiliation
Hospital Vall d'Hebron
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Sanchez Eva, Dr
Organizational Affiliation
Hospital Vall d'Hebron
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital Juan Canalejo
City
A Coruña
Country
Spain
Facility Name
Hospital Ntra. Sra. de Sonsoles
City
Avila
Country
Spain
Facility Name
Hospital germans Trias i Pujol
City
Badalona
Country
Spain
Facility Name
Centro Médico Teknon
City
Barcelona
Country
Spain
Facility Name
Hospital Sant Pau
City
Barcelona
Country
Spain
Facility Name
Hospital Vall d'Hebron
City
Barcelona
Country
Spain
Facility Name
Hospital General Yagüe
City
Burgos
Country
Spain
Facility Name
Hospital de Jerez
City
Cadiz
Country
Spain
Facility Name
Complejo hospitalario Xeral-Calde
City
Lugo
Country
Spain
Facility Name
Hospital Clínico Universitario San Carlos
City
Madrid
Country
Spain
Facility Name
Hospital Ramón y Cajal
City
Madrid
Country
Spain
Facility Name
Hospital Virgen de la Victoria
City
Málaga
Country
Spain
Facility Name
Hosptal Joan XXIII
City
Tarragona
Country
Spain
Facility Name
Hospital Verge de la Cinta
City
Tortosa
Country
Spain
Facility Name
Hospital Rio Hortega
City
Valladolid
Country
Spain
Facility Name
Hospital Clinico Lozano Blesa
City
Zaragoza
Country
Spain
12. IPD Sharing Statement
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Links:
URL
http://www.aehh.org
Description
Spanish association of Haematology
Learn more about this trial
Fludarabine, Cytarabine, Topotecan in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia
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