Acute Myeloid LeukemiaPhase 1/2NCT00651781
Velcaflagida in Relapsed or Refractary Acute Myeloid Leukemia
A Phase 1/2 study testing Bortezomib in people with Acute Myeloid Leukemia, run by PETHEMA Foundation at 13 sites in Spain.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- Bortezomib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 13 sitesSpain
- Study dates
- Apr 2008to Feb 2013
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
Spain13 sites
Hospital Juan Canalejo
A Coruña
Hospital Germans Trias I Pujol
Badalona
Hospital Clinic y Provincial de Barcelona
Barcelona
Hospital Santa Creu y Sant Pau.Barcelona
Barcelona
Hospital Vall d´hebron
Barcelona
Hospital 12 de Octubre
Madrid
Hospital Clínico San Carlos.
Madrid
Hospital Ramón y Cajal. Madrid
Madrid
Hospital Morales Messeguer
Murcia
Hospital Central de Asturias
Oviedo
Hospital Universitario de Salamanca
Salamanca, Salamanca
Hospital La Fe de Valencia
Valencia
Hospital Lozano Blesa
Zaragoza
About this study
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).
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.
Read more
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.
Read the detailed 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.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- Bortezomib
- Keywords
- Acute Myeloid Leukemia, Relapsed, Refractory
- Medical subject headings
- Leukemia, Myeloid, Acute, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BortezomibDrug
2 times per week of Velcade administration.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Drug: Bortezomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 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
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2008 (estimated)
- Study startApr 2008
- Primary completionJan 2013
- Study completionFeb 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- PETHEMA Foundation
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- San Miguel Jesús, Dr, Study chair, PETHEMA Foundation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00651781
- Sponsor's protocol ID
- Nº EudraCT: 2005-004370-24
- Other IDs
- IIS-VEL-EU-070/26866138CAN2015
- Status last verified
- Feb 2013
- First submitted
- 31 Mar 2008
- Last updated
- 28 Feb 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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).
- ClinicalTrials.gov ID
- NCT00651781
- Acronym / sponsor ID
- Nº EudraCT: 2005-004370-24
- Conditions
- Acute Myeloid Leukemia
- Keywords
- Acute Myeloid Leukemia, Relapsed, Refractory
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- PETHEMA FoundationUniversity, hospital or other
- Study start
- Apr 2008
- Primary completion
- Jan 2013 (actual)
- Study completion
- Feb 2013 (actual)
- First posted
- 3 Apr 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: BortezomibPhase 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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).
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bortezomib2 times per week of Velcade administration. | Drug | 1 |
Primary outcome
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.
Time frame: 1 year
2 secondary outcomes
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
Time frame: 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
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2013.
- Spanish association of HaematologyLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
San Miguel Jesús, Dr study chair
PETHEMA Foundation
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Bortezomib in people with Acute Myeloid Leukemia, run by PETHEMA Foundation at 13 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Feb 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2013.