Velcaflagida in Relapsed or Refractary Acute Myeloid Leukemia

Acute Myeloid Leukemia Clinical Trial

Official title:

A Phase I/II National, Open-label, Multicenter Study of Bortezomib (Velcade) in Combination With FLAG-IDA (VFLAG- IDA) in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00651781
• Other study ID #: Nº EudraCT: 2005-004370-24
• Secondary ID: IIS-VEL-EU-070/2
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: March 31, 2008
• Last updated: February 27, 2013
• Start date: April 2008
• Est. completion date: February 2013

Study information

• Verified date: February 2013
• Source: PETHEMA Foundation
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

The primary aim of this study is:

• To analyze the efficacy (in order to evaluate the response) of a sequential treatment scheme of Bortezomib in combination with Fludarabine,Cytarabine and Idarubicin continued with Bortezomib monotherapy for patients with relapsed or refractory AML ≥18 years old.

The safety aim of this study is:

• To evaluate the safety and tolerance of the sequential treatment scheme proposed with Bortezomib combined with Fludarabine, Cytarabine and Idarubicin and in monotherapy, measured on clinical toxicities and laboratory incidences.

The biological aim of this study is:

• To evaluate the Minimal Residual Disease (MRD)impact that will be monitored by multiparametric flow cytometry carried out at different moments during the treatment.

Description:

Initially a phase I will be performed to determine the appropriate dose of Cytarabine to be used in Flag-Ida regimen in combination with Velcade; for that reason, first 9 patients will be distributed to 3 different cohorts with 3 patients in each cohort, which will be treated at each Cytarabine dose level (200 mg/m2-500 mg/m2-1000 mg/m2)in combination with the other drugs from Flag scheme and the fixed dose of Velcade at 1,3 mg/m2.

Once the appropriate Cytarabine dose is determined,the recruitment will be completed with 40 patients and evaluations and visits program will be realized in three periods: Pre-treatment, Treatment and Follow-up.

The Pre-treatment includes Screening and baseline visits. After providing informed consent, patients will be evaluated for study eligibility.

Eligible patients included in the study will receive the first cycle, which consist of Fludarabine, Cytarabine and Idarubicin in combination with 2 times per week of Velcade administration. Each 28-day treatment, patients will be evaluated, and in absence of disease progression or unacceptable toxicity, patients will start second cycle with Bortezomib in monotherapy two times per week followed by a 10 days rest period. That is, patients who response with acceptable toxicity will receive the combined sequential scheme twice (as induction and consolidation).

Patients will be evaluated the day 1 of each cycle,during the treatment period, in order to know the response before carrying on the treatment. Once the Treatment period is completed, patients will be evaluated during the Follow-up period, one monthly visit in year 1, and every 3 months for 3 next years. On each center criteria, autologous/allogeneic transplant can be planned depending on age and HLA identical sibling donor make it possible: it will be done following the sequential scheme (Velcade-Flag-Ida and Velcade in monotherapy); if the patient is not candidate for a transplant or has no donor, he/she will receive 2 sequential scheme.

Safety will be evaluated through all adverse events monitoring, physical exploration, vital signs, hematimetric and biochemical analysis. The treatment response will be evaluated using Cheson's standardized criteria, and MRD impact will be necessary evaluated the day 1 of each new cycle before to carry on the treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: February 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• The patient must, according with investigator criteria,be able to comply with all the protocol requirements.

• The patient must sign voluntarily the informed consent before the performance of any study related procedure not part of usual medical care, with the knowledge that can leave the study the moment he/she wants, without prejudice to later medical care.

• Age ¡Ý 18 years old.

• Patient must be diagnosed with AML according World Health Organization (WHO)18 criteria (see Appendix 7).

• Patient with refractory AML after standard therapy, or relapsed AML after standard therapy or hematopoietic progenitors transplant (autologous or allogenic).

• Patient has a ECOG performance status <= 2 (see Appendix 5).

• Patient has the following laboratory values before Baseline visit:

1. Platelet count = 30000/mm3 (transfusion allowed), hemoglobin = 8 g/dl (transfusion allowed) and absolute neutrophil count = 0.750/mm3. Lower values are accepted if they are caused by bone marrow infiltration.

2. Aspartate transaminase (AST): = 2.5 x the upper limit of normal.

3. Alanine transaminase (ALT): = 2.5 x the upper limit of normal.

4. Total bilirubin: =1.5 x the upper limit of normal.

5. Serum creatinine value = 2 mg/dl.

• Negative pregnant test for fertile females

Exclusion Criteria:

Prior Bortezomib therapy.

• Promyelocytic AML.

• Patient has > Grade 2 peripheral neuropathy within 14 days before enrollment.

• Fertile patient is not going to use a medical effective contraceptive method during the trial.

• Patient has received other investigational drugs within 30 days before enrollment.

• Patient is known to be seropositive for the human immunodeficiency virus (HIV), Hepatitis B surface antigen-positive or active hepatitis C infection.

• Patient had a myocardial infarction within 6 months of enrollment or has New York Heart Association (NYHA) Class III or IV, heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias,or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.

• Patient is enrolled in another clinical research study and/or is receiving an investigational agent for any reason.

• Pregnant or breast-feeding women.

Study Design

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Bortezomib
2 times per week of Velcade administration.

Locations

Country	Name	City	State
Spain	Hospital Germans Trias I Pujol	Badalona
Spain	Hospital Clinic y Provincial de Barcelona	Barcelona
Spain	Hospital Santa Creu y Sant Pau.Barcelona	Barcelona
Spain	Hospital Vall d´hebron	Barcelona
Spain	Hospital Juan Canalejo	La Coruña
Spain	Hospital 12 de Octubre	Madrid
Spain	Hospital Clínico San Carlos.	Madrid
Spain	Hospital Ramón y Cajal. Madrid	Madrid
Spain	Hospital Morales Messeguer	Murcia
Spain	Hospital Central de Asturias	Oviedo
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital La Fe de Valencia	Valencia
Spain	Hospital Lozano Blesa	Zaragoza

Sponsors (1)

Lead Sponsor	Collaborator
PETHEMA Foundation

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy (in order to evaluate the response) of a sequential treatment scheme of Bortezomib in combination with Fludarabine,Cytarabine and Idarubicin continued with Bortezomib monotherapy for patients with relapsed or refractory AML =18 years old.		1 year	No
Secondary	Evaluate the safety and tolerance of the sequential treatment scheme proposed with Bortezomib combined with Fludarabine, Cytarabine and Idarubicin and in monotherapy, measured on clinical toxicities and laboratory incidences		1 year	Yes
Secondary	Evaluate the Minimal Residual Disease (MRD)impact that will be monitored by multiparametric flow cytometry carried out at different moments during the treatment		1 year	No

External Links

•   Pethema Foundation web
•   Spanish association of Haematology