Velcaflagida in Relapsed or Refractary Acute Myeloid Leukemia

NCT00651781 | Completed Phase 1 DMC

• 2 other identifiers: Nº EudraCT: 2005-004370-24IIS-VEL-EU-070/26866138CAN2015
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 13

Brief 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.

Conditions

Acute Myeloid Leukemia

Keywords

Acute Myeloid Leukemia; Relapsed; Refractory

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (2)

• 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

• 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

Study Arms (1)

1

EXPERIMENTAL

Phase I:3 dose levels Cytarabine (200 mg/m2- 500 mg/m2-1000 mg/m2) with scheme Flag-Ida in combination with Velcade until determinate the appropriate dose. Phase II: 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).

Drug: Bortezomib

Interventions

Bortezomib DRUG

2 times per week of Velcade administration.

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.
• Aspartate transaminase (AST): ≤ 2.5 x the upper limit of normal.
• Alanine transaminase (ALT): ≤ 2.5 x the upper limit of normal.
• Total bilirubin: ≤1.5 x the upper limit of normal.
• Serum creatinine value ≤ 2 mg/dl.
• Negative pregnant test for fertile females

You may not qualify if:

• 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.

Sponsors & Collaborators

• PETHEMA Foundation: lead

Study Sites (13)

Hospital Universitario de Salamanca

Salamanca, Salamanca, Spain

Location

Hospital Juan Canalejo

A Coruña, Spain

Location

Hospital Germans Trias I Pujol

Badalona, Spain

Location

Hospital Clinic y Provincial de Barcelona

Barcelona, Spain

Location

Hospital Santa Creu y Sant Pau.Barcelona

Barcelona, Spain

Location

Hospital Vall d´hebron

Barcelona, Spain

Location

Hospital 12 de Octubre

Madrid, Spain

Location

Hospital Clínico San Carlos.

Madrid, Spain

Location

Hospital Ramón y Cajal. Madrid

Madrid, Spain

Location

Hospital Morales Messeguer

Murcia, Spain

Location

Hospital Central de Asturias

Oviedo, Spain

Location

Hospital La Fe de Valencia

Valencia, Spain

Location

Hospital Lozano Blesa

Zaragoza, Spain

Location

Related Links

• Spanish association of Haematology

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Recurrence

Interventions

Bortezomib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• San Miguel Jesús, Dr

  PETHEMA Foundation

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2008
• First Posted: April 3, 2008
• Study Start: April 1, 2008
• Primary Completion: January 1, 2013
• Study Completion: February 1, 2013
• Last Updated: February 28, 2013

Record last verified: 2013-02

Locations

ES (13)