SMD_FLAG-IDA_98: FLAG-IDA in Induction Treatment of High Risk Myelodysplastic Syndromes or Secondary Acute Myeloblastic Leukemia

Myelodysplastic Syndrome Clinical Trial

— FLAG-IDA  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00487448
• Other study ID #: SMD_FLAG-IDA_98
• Status: Completed
• Phase: Phase 4
• First received: June 15, 2007
• Last updated: November 17, 2008
• Start date: July 1998
• Est. completion date: June 2007

Study information

• Verified date: November 2008
• Source: PETHEMA Foundation
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: June 2007
• Est. primary completion date: May 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 75 Years

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Myeloblastic Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• Fludarabine

• Cytarabine

• G-CSF

• Idarubicin

Procedure:
• Peripheral blood stem cell transplantation

• Bone marrow transplantation

Locations

Country	Name	City	State
Spain	Hospital de la Ribera	Alzira
Spain	Hospital Germans Trias i Pujol	Badalona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital Puerta del Mar	Cadiz
Spain	Hospital del SAS	Jerez de la Frontera
Spain	Hospital de Leon	Leon
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Morales Messeguer	Murcia
Spain	Hospital Central de Asturias	Oviedo
Spain	Hospital Clínico de Salamanca	Salamanca
Spain	Hospital Arnau de Vilanova	Valencia
Spain	Hospital Dr. Pesset	Valencia
Spain	Hospital Universitario La Fe	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
PETHEMA Foundation

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluation of efficacy of study treatment: complete remission rate, remission duration and global survival		2 years
Secondary	Evaluation of neutropenia and thrombocytopenia duration post-induction chemotherapy		3 months
Secondary	Determinate the percentage of patients that reach the transplantation		3 months
Secondary	Determinate the toxicity of induction regimen and the chemotherapy postremission		1 year

External Links

•   Pethema Foundation web
•   Spanish association of Haematology