LeukemiaPhase 1/2AML-14ANCT00838240
Clofarabine, Cytarabine, and Idarubicin in Treating Patients With Intermediate-Risk or High-Risk Acute Myeloid Leukemia or High-Risk Myelodysplasia
A Phase 1/2 study testing clofarabine, cytarabine and idarubicin in people with Leukemia and Myelodysplastic Syndromes, run by European Organisation for Research and Treatment of Cancer - EORTC at 10 sites in 5 countries.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as clofarabine, cytarabine, and idarubicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Leukemia, Myelodysplastic Syndromes
- What is being tested?
- clofarabine, cytarabine and idarubicin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 114 participants
- Where
- 10 sitesin 5 countries
- Study dates
- Nov 2008to Dec 2012
- 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 to 60 years
- All sexes
- No healthy volunteers
- Adult
DISEASE CHARACTERISTICS:
- Diagnosis of 1 of the following by WHO criteria:
- Acute myeloid leukemia (AML) (≥ 20% bone marrow blasts by bone marrow aspiration or biopsy)
- No acute promyelocytic leukemia (M3)
- All cytogenetic groups allowed, except for the following:
- t(15;17)
- t(8;21) or inv(16) AND a WBC count at diagnosis of < 100,000/μL
- Primary or secondary AML allowed, including AML after myelodysplasia (MDS)
- High-risk MDS (≥ 10% bone marrow blasts by bone marrow aspiration or biopsy)
- No chronic myelogenous leukemia in blast crisis or AML supervening a myeloproliferative disorder
- Previously untreated disease, except for ≤ 14 days of hydroxyurea
- No CNS leukemia
PATIENT CHARACTERISTICS:
- WHO performance status 0-2
- Serum creatinine ≤ 1.0 mg/dL or glomerular filtration rate > 60 mL/min
- AST/ALT ≤ 2.5 times upper limit of normal (ULN)
- ALP ≤ 2.5 times ULN
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective barrier contraception during and for ≥ 3 months after completion of study treatment
- No active uncontrolled infection
- No HIV positivity
- No psychological, familial, sociological, or geographical conditions precluding compliance with study treatment or follow up
- No concurrent severe uncontrolled cardiovascular disease (i.e., symptomatic congestive heart failure or symptomatic ischemic heart disease [NYHA class III-IV])
- No concurrent malignant disease
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No concurrent cytotoxic drugs or experimental therapies (e.g., antiangiogenic drugs, tyrosine kinase inhibitors)
Trial locations and contacts
10 sites in 5 countries.
Hilde Breyssens contact
10 sites in 5 countries
Belgium3 sites, 3 recruiting
- Recruiting
A.Z. Sint-Jan
Bruges
Dominik Selleslag
- Not yet recruiting
Institut Jules Bordet
Brussels
Dominique Bron
- Not yet recruiting
CHU Sart-Tilman
Liège
Frédéric Baron
Netherlands3 sites, 2 recruiting
- Recruiting
Jeroen Bosch Ziekenhuis
's-Hertogenbosch
Hans Pruijt
- Active, not recruiting
Leiden University Medical Center
Leiden
- Recruiting
Radboud University Nijmegen Medical Center
Nijmegen
Petra Muus
Italy2 sites, 2 recruiting
- Recruiting
Azienda Ospedallera Universitaria - Policlinico Tor Vergata
Roma
Sergio Amadori
- Recruiting
Univesita Degli Studi "La Sapienza"
Roma
Giovanna Meloni
Croatia1 site, 1 recruiting
- Not yet recruiting
University Hospital Rebro
Zagreb
Boris Labar
France1 site, 1 recruiting
- Not yet recruiting
Hôpital Saint Antoine AP-HP
Paris
Olivier Legrand
About this study
Official title: Clofarabine in Combination With a Standard Remission Induction Regimen (AraC and Idarubicin) in Patients 18-60 Years Old With Previously Untreated Intermediate and Bad Risk Acute Myelogenous Leukemia (AML) or High Risk Myelodysplasia (MDS) : a Phase I-II Study of the EORTC-LG and GIMEMA (AML-14A Trial)
RATIONALE: Drugs used in chemotherapy, such as clofarabine, cytarabine, and idarubicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.
PURPOSE: This randomized phase I/II trial is studying the side effects and best dose of clofarabine and to see how well it works when given together with cytarabine and idarubicin in treating patients with intermediate-risk or high-risk acute myeloid leukemia or high-risk myelodysplasia.
Read the detailed description
OBJECTIVES:
Primary
- To determine the optimum dose of clofarabine in combination with cytarabine and idarubicin in patients with previously untreated intermediate- and high-risk acute myeloid leukemia or high-risk myelodysplasia. (Phase I)
- To determine the safety and tolerance of this regimen in order to determine the recommended phase II dose. (Phase I)
- To explore the antitumor activity of this regimen in these patients. (Phase II)
- To determine the activity expressed as complete remission (CR)/CR with incomplete hematopoietic recovery (CRi) rate following induction therapy. (Phase II)
Secondary
- To determine the activity expressed as CR/CRi rate following induction (1 or 2 courses) and consolidation therapy. (Phase I)
- To determine hematopoietic recovery (platelets and neutrophils) after induction and consolidation therapy.
- To determine safety and tolerability of this regimen. (Phase II)
- To determine activity expressed as CR/CRi rate after consolidation therapy. (Phase II)
- To determine feasibility of blood CD34 harvesting after consolidation therapy. (Phase II)
- To determine disease-free and overall survival from CR/CRi. (Phase II)
OUTLINE: This is a multicenter, phase I, dose-escalation study of clofarabine followed by an randomized phase II study. Patients are stratified according to center, and presence of poor prognostic features (WBC at diagnosis ≥ 100,000/μL vs presence of very high risk cytogenetic features -5/5q-, -7/7q-, presence of complex abnormalities [> 3 abnormalities], 3q, t[6;9], or t[9;22]). Patients are randomized to 1 of 2 treatment arms.
- Induction therapy:
- Arm I: Patients receive idarubicin IV over 5 minutes on days 1, 3, and 5, cytarabine IV continuously on days 1-10, and clofarabine IV over 1 hour on days 2, 4, 6, 8, and 10.
- Arm II: Patients receive idarubicin IV and cytarabine IV as in arm I. Patients also receive clofarabine IV by push injection over 10 minutes on days 2, 4, 6, 8, and 10.
- Consolidation therapy: Patients receive cytarabine IV over 2 hours every 12 hours on days 1-6 and idarubicin IV over 5 minutes once daily on days 4-6.
After completion of study therapy, patients are followed periodically for 12 months.
- Conditions
- Leukemia, Myelodysplastic Syndromes
- Being tested
- clofarabine, cytarabine, idarubicin
- Keywords
- adult acute minimally differentiated myeloid leukemia (M0), adult acute myeloblastic leukemia without maturation (M1), adult acute myeloblastic leukemia with maturation (M2), adult acute myelomonocytic leukemia (M4), adult acute monoblastic leukemia (M5a), adult acute monocytic leukemia (M5b), adult erythroleukemia (M6a), adult pure erythroid leukemia (M6b), adult acute megakaryoblastic leukemia (M7), adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), adult acute myeloid leukemia with inv(16)(p13;q22), untreated adult acute myeloid leukemia, de novo myelodysplastic syndromes, secondary acute myeloid leukemia
- Medical subject headings
- Leukemia, Myelodysplastic Syndromes, Leukemia, Myeloid, Acute, Leukemia, Myelomonocytic, Acute, Leukemia, Monocytic, Acute, Leukemia, Erythroblastic, Acute, Leukemia, Megakaryoblastic, Acute, Congenital Abnormalities
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
clofarabineDrug
Given IV
cytarabineDrug
Given IV
idarubicinDrug
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | Patients receive idarubicin IV over 5 minutes on days 1, 3, and 5, cytarabine IV continuously on days 1-10, and clofarabine IV over 1 hour on days 2, 4, 6, 8, and 10. Receives: Drug: clofarabine; Drug: cytarabine; Drug: idarubicin |
| Arm II | Experimental | Patients receive idarubicin IV and cytarabine IV as in arm I. Patients also receive clofarabine IV by push injection over 10 minutes on days 2, 4, 6, 8, and 10. Receives: Drug: clofarabine; Drug: cytarabine; Drug: idarubicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Toxicity as assessed by CTCAE v3.0 (Phase I)
Response rate (Phase II)
Secondary outcomes (6)
Toxicity as assessed by CTCAE v3.0 (Phase II)
Response rate (Phase I)
Duration of survival
Duration of survival from complete remission (CR)/CR with incomplete hematopoietic recovery (CRi) rate
Disease-free survival from CR/CRi
Incidence of relapse and incidence of death in CR/CRi
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2009 (estimated)
- Study startNov 2008
- Primary completionDec 2012 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by European Organisation for Research and Treatment of Cancer - EORTCThe sponsor's other registered studies.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 114 participants (estimated)
Sponsor and investigators
- Sponsor type
- Research network
- Collaborators
- Gruppo Italiano Malattie EMatologiche dell'Adulto
- Responsible party
- Sponsor
- Investigators
- Roel Willemze, Principal investigator, EORTC (Phase I) - Leiden University Medical Center, NLDominik Selleslag, Principal investigator, EORTC (Phase II) - AZ Sint-Jan, BEGiovanna Meloni, Principal investigator, GIMEMA (Phase I & II) - Universita Degli Studi "La Sapienza", IT
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00838240
- Sponsor's protocol ID
- EORTC-06061
- Other IDs
- EORTC-06061, EU-20905, 2006-004912-28, GIMEMA-AML-14A
- Acronym
- AML-14A
- Status last verified
- Jul 2012
- First submitted
- 5 Feb 2009
- Last updated
- 20 Jul 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clofarabine in Combination With a Standard Remission Induction Regimen (AraC and Idarubicin) in Patients 18-60 Years Old With Previously Untreated Intermediate and Bad Risk Acute Myelogenous Leukemia (AML) or High Risk Myelodysplasia (MDS) : a Phase I-II Study of the EORTC-LG and GIMEMA (AML-14A Trial)
- ClinicalTrials.gov ID
- NCT00838240
- Acronym / sponsor ID
- AML-14A / EORTC-06061
- Conditions
- Leukemia, Myelodysplastic Syndromes
- Keywords
- adult acute minimally differentiated myeloid leukemia (M0), adult acute myeloblastic leukemia without maturation (M1), adult acute myeloblastic leukemia with maturation (M2), adult acute myelomonocytic leukemia (M4), adult acute monoblastic leukemia (M5a), adult acute monocytic leukemia (M5b), adult erythroleukemia (M6a), adult pure erythroid leukemia (M6b)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 114 participants (estimated)
- Lead sponsor
- European Organisation for Research and Treatment of Cancer - EORTCResearch network
- Collaborators
- Gruppo Italiano Malattie EMatologiche dell'Adulto
- Study start
- Nov 2008
- Primary completion
- Dec 2012 (estimated)
- First posted
- 6 Feb 2009 (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.
RATIONALE: Drugs used in chemotherapy, such as clofarabine, cytarabine, and idarubicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.
PURPOSE: This randomized phase I/II trial is studying the side effects and best dose of clofarabine and to see how well it works when given together with cytarabine and idarubicin in treating patients with intermediate-risk or high-risk acute myeloid leukemia or high-risk myelodysplasia.
Detailed description
OBJECTIVES:
Primary
- To determine the optimum dose of clofarabine in combination with cytarabine and idarubicin in patients with previously untreated intermediate- and high-risk acute myeloid leukemia or high-risk myelodysplasia. (Phase I)
- To determine the safety and tolerance of this regimen in order to determine the recommended phase II dose. (Phase I)
- To explore the antitumor activity of this regimen in these patients. (Phase II)
- To determine the activity expressed as complete remission (CR)/CR with incomplete hematopoietic recovery (CRi) rate following induction therapy. (Phase II)
Secondary
- To determine the activity expressed as CR/CRi rate following induction (1 or 2 courses) and consolidation therapy. (Phase I)
- To determine hematopoietic recovery (platelets and neutrophils) after induction and consolidation therapy.
- To determine safety and tolerability of this regimen. (Phase II)
- To determine activity expressed as CR/CRi rate after consolidation therapy. (Phase II)
- To determine feasibility of blood CD34 harvesting after consolidation therapy. (Phase II)
- To determine disease-free and overall survival from CR/CRi. (Phase II)
OUTLINE: This is a multicenter, phase I, dose-escalation study of clofarabine followed by an randomized phase II study. Patients are stratified according to center, and presence of poor prognostic features (WBC at diagnosis ≥ 100,000/μL vs presence of very high risk cytogenetic features -5/5q-, -7/7q-, presence of complex abnormalities [> 3 abnormalities], 3q, t[6;9], or t[9;22]). Patients are randomized to 1 of 2 treatment arms.
- Induction therapy:
- Arm I: Patients receive idarubicin IV over 5 minutes on days 1, 3, and 5, cytarabine IV continuously on days 1-10, and clofarabine IV over 1 hour on days 2, 4, 6, 8, and 10.
- Arm II: Patients receive idarubicin IV and cytarabine IV as in arm I. Patients also receive clofarabine IV by push injection over 10 minutes on days 2, 4, 6, 8, and 10.
- Consolidation therapy: Patients receive cytarabine IV over 2 hours every 12 hours on days 1-6 and idarubicin IV over 5 minutes once daily on days 4-6.
After completion of study therapy, patients are followed periodically for 12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Drug: clofarabine, Drug: cytarabine, Drug: idarubicinPatients receive idarubicin IV over 5 minutes on days 1, 3, and 5, cytarabine IV continuously on days 1-10, and clofarabine IV over 1 hour on days 2, 4, 6, 8, and 10. |
| Arm II | Experimental | Drug: clofarabine, Drug: cytarabine, Drug: idarubicinPatients receive idarubicin IV and cytarabine IV as in arm I. Patients also receive clofarabine IV by push injection over 10 minutes on days 2, 4, 6, 8, and 10. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
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 |
|---|---|---|
| clofarabineGiven IV | Drug | Arm I, Arm II |
| cytarabineGiven IV | Drug | Arm I, Arm II |
| idarubicinGiven IV | Drug | Arm I, Arm II |
Primary outcome
Toxicity as assessed by CTCAE v3.0 (Phase I)
Response rate (Phase II)
6 secondary outcomes
Toxicity as assessed by CTCAE v3.0 (Phase II)
Response rate (Phase I)
Duration of survival
Duration of survival from complete remission (CR)/CR with incomplete hematopoietic recovery (CRi) rate
Disease-free survival from CR/CRi
Incidence of relapse and incidence of death in CR/CRi
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2012.
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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.
Hilde Breyssens contact
Roel Willemze principal investigator
EORTC (Phase I) - Leiden University Medical Center, NL
Dominik Selleslag principal investigator
EORTC (Phase II) - AZ Sint-Jan, BE
Giovanna Meloni principal investigator
GIMEMA (Phase I & II) - Universita Degli Studi "La Sapienza", IT
10 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing clofarabine, cytarabine and idarubicin in people with Leukemia and Myelodysplastic Syndromes, run by European Organisation for Research and Treatment of Cancer - EORTC at 10 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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: status not confirmed, as of the sponsor's last update on 20 Jul 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Belgium, Netherlands, Italy, Croatia, France. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Hilde Breyssens (hilde.breyssens@eortc.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Toxicity as assessed by CTCAE v3.0 (Phase I). The study lists 2 primary outcomes in all. 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 20 Jul 2012.