Clinical trial NCT00487448: SMD_FLAG-IDA_98: FLAG-IDA in Induction Treatment of High Risk Myelodysplastic Syndromes or Secondary Acute Myeloblastic Leukemia
Official title: FLAG-IDA Chemotherapy Induction Follow by Intensive Chemotherapy Postremission +/- Autologous Hemopoietic Stem Cell Transplantation or Bone Marrow Transplantation in Patients With High Risk Myelodysplastic Syndromes or Secondary Acute Myeloblastic Leukemia.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Myelodysplastic Syndrome
Acute Myeloblastic Leukemia
Keywords: Myelodysplastic Syndrome
Chemotherapy
Peripheral blood stem cells transplantation
Bone marrow transplantation
Secondary Acute Myeloblastic Leukemia
Lead sponsor: PETHEMA Foundation
Sponsor class: OTHER
First posted: 2007-06-18
Enrollment: 200
Sex: ALL
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Association group of therapeutic specialities authorized in a remission induction treatment(FLAG-IDA: fludarabine, cytarabine, G-CSF (lenograstim) and idarubicin) and an intensive postremission treatment with authorized therapeutic association specialities and with/without Autologous Hemopoietic Stem Cell Transplantation or Bone Marrow Transplantation in Patients With High Risk Myelodysplastic Syndromes or Secondary Acute Myeloblastic Leukemia.

Detailed description: To reach the first remission, the patients receive one cycle of FLAG-IDA combination, that include: Fludarabine 30 mg/m 2 /d Days 1 to 4 in IV perfusion during 30 minutes; Cytarabine 2 g/m 2/d, days 1 to 4 in IV perfusion during 4 hours glycosylate G-CSF 300 µg/m 2/d, days -1 to 5 SC; lenograstim 263 µg/d f, days 11 until absolute neutrophil count \>1x10 9 /L SC; Idarubicin 10 mg/m2/d, days 1 to 3 IV bolus (15 minutes)

Patients who don't reach complete remission (CR) are considered as a failure and must go out of study.

The participating centres should decide if the patients under 35 years in CR and with unrelated donor, are excluded to be treated with allogenic transplantation or they continue in the study.

The patients who reach CR will receive one consolidation cycle with IDA-ARAC + G-CSF combination:

Idarubicin 10 mg/m2/d, days 1 to 3 IV bolus (15 minutes); Cytarabine 200 mg/m 2/d days 1 to 5 IV in 24 hours continuous perfusion; glycosylate G-CSF(lenograstim) 263 µg, days 12 until absolute neutrophil count \>1x10 9 /L SC

The patients younger than 65 years that is possible, will done an autologous transplantation with peripheral stem blood cells or combined with peripheral stem blood cells and bone marrow stem cells. The preparative regimen recommended are BuCy2 (busulfan-cyclophosphamide) and ICT-Cy (irradiation corporal total-cyclophosphamide).

The patients older than 65 years will receive one intensification cycle with carboplatin and G-CSF.

The peripheral blood stem cells collection should be done during the recuperation period after consolidation chemotherapy in patients under 65 years. The leucapheresis procedure could be determinate for in each center participating.

The patients with no sufficient collection of stem cells during the regeneration period post-chemotherapy of consolidation, will receive glycosylate G-CSF (lenograstim, Granocyte®)10 µg/kg/d SC during 5 days, doing the collection cells on days 5 and 6. In the situations that the peripheral blood stem cells are non satisfactory, will realize a collection of bone marrow stem cells.

The realization of Peripheral Blood Stem Cell Transplantation or combined, depends the number of cells obtained in the collection procedures.In the situations that didn't reach sufficient number of cells (peripheral blood and bone marrow), should be administered one chemotherapy intensification cycle.

The preparative regimen is established by each participating center, but is recommended one of next:

1. BuCy2 (busulfan 16 mg/kg follow by cyclophosphamide 120 mg/kg),
2. Total-body irradiation 12 Gy and cyclophosphamide 120 mg/kg.

Intensification treatment:

Patients older than 65 years and younger than 65 who the collection cells for transplantation is not enough, will receive one cycle of intensification chemotherapy with carboplatin and glycosylate G-CSF:

Carboplatin 300 mg/m2/d days 1 to 4 IV in 24 hours continuous perfusion glycosylate G-CSF (lenograstim)263 µg f days 11 until absolute neutrophil count \>1x10 9 /L, SC

Eligibility criteria: Inclusion Criteria:

* Age \< 75 years
* Diagnosis of Myelodysplastic Syndrome in order to FAB criteria, excluding patients with chronic myeloid leukemia.
* IPI \> 1 (High risk or Intermedia risk-2) and/or IPE equal or \> 3 (High risk o Intermedia risk) or secondary acute myeloid leukemia.
* Resolved toxicity for previous treatments received to Myelodysplastic Syndrome .
* Myelodysplastic Syndrome de novo.

Exclusion Criteria:

* Associated neoplasia.
* Chronic disease that can limit the patient follow up protocol (cardiovascular disease, active infection uncontrolled, etc.).
* Age \< 55 years with related donor HLA compatible.
* Use an investigational drug in the 30 previous days.
* Previous treatment with chemotherapy agents.
* Simultaneous treatment during the study with other drugs not allowed in the protocol.
* Bilirubin \> 2 mg/dL and GPT \>2 times the normal value.
* Creatinine \> 2 mg/dL.
* Hypersensibility to agents used in the protocol.
* Secondary MDS to chemo-radiotherapy .
* HIV positive.
* Chronic myeloblastic leukemia

Primary outcomes:
measure: Evaluation of efficacy of study treatment: complete remission rate, remission duration and global survival
timeFrame: 2 years
Secondary outcomes:
measure: Evaluation of neutropenia and thrombocytopenia duration post-induction chemotherapy
timeFrame: 3 months
measure: Determinate the percentage of patients that reach the transplantation
timeFrame: 3 months
measure: Determinate the toxicity of induction regimen and the chemotherapy postremission
timeFrame: 1 year
Other outcomes:
Locations:
city: Alzira
country: Spain
facility: Hospital de la Ribera
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Cadiz
country: Spain
facility: Hospital Puerta del Mar
city: Jerez de la Frontera
country: Spain
facility: Hospital del SAS
city: Leon
country: Spain
facility: Hospital de Leon
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Murcia
country: Spain
facility: Hospital Morales Messeguer
city: Oviedo
country: Spain
facility: Hospital Central de Asturias
city: Salamanca
country: Spain
facility: Hospital Clínico de Salamanca
city: Valencia
country: Spain
facility: Hospital Arnau de Vilanova
city: Valencia
country: Spain
facility: Hospital Dr. Pesset
city: Valencia
country: Spain
facility: Hospital Universitario La Fe
Study officials:
affiliation: Hospital La Fe
name: Sanz Guillermo, Dr
role: STUDY_CHAIR
affiliation: Hospital La Fe
name: Sanz Miguel Angel, Dr
role: PRINCIPAL_INVESTIGATOR
References: