Clofarabine and Low-dose Cytarabine Followed by Consolidation Therapy in AML Patients Age Greater Than or Equal to 60 Years

April 4, 2014 updated by: PETHEMA Foundation

Multicentric Phase II Trial, Prospective, Open, Single Group, to Discuss Induction Therapy With a Combination of Clofarabine and Low-dose Cytarabine Followed by Consolidation Therapy With Clofarabine and Low-dose Cytarabine for the Treatment of AML Patients Age Greater Than or Equal to 60 Years

Primary outcome measure:

Evaluate the efficacy in terms of complete responses of induction therapy and first-line consolidation of Clofarabine and low-dose Cytarabine with AML patients aged 60 years or more. The first efficacy objective is evaluate the overall remission rate (TRG), where general reference (RG) is defined as a patient who achieved complete remission (CR) or complete remission with inadequate platelet recovery (CPR).

Secondary outcome measures:

  • To evaluate disease-free survival (DFS)
  • Evaluate the overall survival (OS)
  • To evaluate the safety and tolerability of clofarabine and duration, severity and relationship of adverse events (AEs) occurring during treatment
  • To assess the rate of mortality at 30 days (ie, the incidence of deaths occurring between Day 1 and Day 30 of induction cycle)
  • The incidence, intensity (according to the latest version of the CTCAE classification), duration, causality, severity and type of AA

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This protocol corresponds to a multicenter, phase II, open, non randomized, designed to determine the efficacy of clofarabine and low-dose cytarabine combination in AML patients older than or equal to 60 years.

The trial is divided into pre-treatment and treatment (cycle / s of induction and consolidation) periods.The induction cycle consist of clofarabine at 20 mg/m2/day intravenously for 5 consecutive days plus cytarabine subcutaneously at 20 mg/m2/day for 14 consecutive days. If patients do not achieve CR they will receive a second course of induction with the same pattern. Consolidation cycles consist of clofarabine intravenously at 15 mg/m2/day for 5 consecutive days plus cytarabine at 20 mg/m2/day subcutaneously for 7 consecutive days. Patients will receive a maximum of 12 cycles of clofarabine and LDAC. The monitoring phase of survival is made by clinical practice and will continue until all patients have either died or survived two years after the end of treatment visit.

There will be 75 patients older than or equal to 60 years. Patients will be evaluated over the following periods: Pre-treatment and treatment (induction and consolidation).

Pre-treatment phase: includes enrolment visit in which the patient completes the written informed consent to participate in the study.

There will be a selection of patients who have given their written informed consent to join the clinical trial. They must meet all the inclusion criteria and no exclusion.

Treatment phase: Patients should begin treatment within 14 days after signing the informed consent form (ICF). Selection period begins when the ICF is signed and the inclusion period begins when the patient first receives the study drug (ie Day 1 of the induction cycle).

Safety will be evaluated by monitoring all adverse events haematological and not haematological related with the drug's study.

The final visit of treatment will take place at least 45 days after the last dose of study drug administration.

Patients who leave the study prematurely, should have the end of treatment visit within 2 weeks after the decision not to continue to administer the study drug. The final visit should take place within 2 weeks after the visit of the last cycle of treatment.

Off protocol, after making the final visit of, all patients receiving at least one dose of study drug will be subject to monitoring by normal clinical practice, for a minimum of two years from the final visit or until his death

Follow up phase:

The maximum follow-up for all patients is 2 years from the final visit of the last patient included and be conducted on a monthly basis during the first year and quarterly during the second at least, notwithstanding that there may be more visits at discretion of each centre or depending on the clinical features.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
75

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Alicante, Spain
        • Hospital General de Alicante.
      • Barcelona, Spain
        • Hospital Vall d' Hebron
      • Barcelona, Spain
        • Hospital de la Santa Creu i Sant Pau.
      • Barcelona, Spain
        • Hospital Durán i Reynals (Bellvitge).
      • Barcelona, Spain
        • ICO Hospital Germans Trias I Pujol.
      • Córdoba, Spain
        • Hospital Reina Sofía.
      • La Coruña, Spain
        • Hospital Juan Canalejo.
      • Madrid, Spain
        • Hospital Ramon y Cajal.
      • Madrid, Spain
        • Hospital 12 de Octubre.
      • Málaga, Spain
        • Hospital San Pedro de Alcántara.
      • Oviedo, Spain
        • Hospital Central de Asturias.
      • Salamanca, Spain
        • Hospital Clínico Universitario de Salamanca.
      • Sevilla, Spain
        • Hospital Virgen Del Rocio
      • Valencia, Spain
        • Hospital Clínico de Valencia.
      • Valencia, Spain
        • Hospital Universitario La Fe.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

60 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Diagnosis of AML (de novo, secondary, or hematological disorder), according to WHO criteria.
  2. Older than or equal to 60 years
  3. ECOG performance status 0-2

  4. At least one of the following factors:

    • Older than or equal to 70 years
    • Prior hematological disorder (AHD)
    • ECOG performance status 2

    • Unfavorable karyotype (ie, adverse) defined as any cytogenetic profile except the presence of any of the following:

      t(8;21)(q22;q22) inv(16)(p13q22) or t(16;16)(p13;q22) t(15;17)(q22;q12) and variants

  5. Provide written informed consent form.
  6. Being able to comply with study procedures and follow-up evaluations.
  7. Not to be fertile or willing to use a method of birth control during the study until the end of the last visit of the treatment.

  8. Adequate renal and hepatic function as follows:

    • Total bilirubin <= 1,5 x upper of institutional normal limit (ULN) and
    • AST y ALT <=2,5 x ULN and
    • Serum creatinine <=1,0 mg/dL of serum creatinine <01,0 mg/dL, then, glomerular filtration rate (GFR) estimated must be >60 mL/min/1,73 m2 calculated from the equation of the Modification of Diet in Renal Disease (MDRD).

  9. Adequate cardiac function determined by at least one of the following:

    • Left ventricular ejection fraction (LVEF) >=40% measured by echocardiography in Multiple Gated Acquisition (MUGA) scan or isotope angiography or
    • Left ventricular fractional shortening >=22% measured by echocardiography.

Exclusion Criteria:

  1. Diagnosis of acute promyelocytic leukaemia (APL) in French-American-British classification M3º or attending to the WHO classification t(15;17)(q22;q12), (PML/RAR and variants).
  2. Pre-treatment with clofarabine.
  3. Previous treatment for AML or a hematological disorder AHD (excluding palliative care, hydroxyurea, hematopoietic cytokines or lenalidomide [the latter only for a specific AHD]). Hematopoietic cytokines and lenalidomide should not have been administered within the 14 days preceding the first dose of study drug. If it is received any previous treatment for AML or AHD within the time limits allowed, drug-related toxicity, must have recovered to Grade 1 or less before the first dose of study drug.
  4. Previous hematopoietic stem cell transplantation (HSCT).
  5. External beam pelvic radiotherapy.
  6. Have received an investigational product within 30 days before the first dose of study drug. If the patient has received any investigational product before this time, the drug-related toxicity, must have recovered to Grade 1 or less before the first dose of study drug.

  7. Inadequate renal and hepatic function as follows:

    • Total bilirubin >1,5 x institutional upper limit normal (ULN) provided it is not attributable to the very LMA or
    • AST y ALT >2,5 x ULN provided it is not attributable to the very LMA or
    • Serum creatinine >1,0 mg/dL provided that the glomerular filtration rate (GFR) estimated to be ≤60 mL/min/1,73 m2 calculated by the equation of the Modification of Diet in Renal Disease (MDRD).

  8. Inadequate cardiac function determined by at least one of the following:

    • Left ventricular ejection fraction <40% measured by echocardiography in Multiple Gated Acquisition (MUGA) or isotope angiography; or
    • Left ventricular fractional shortening <22% measured by echocardiography.
  9. Poor general condition ECOG 3-4.
  10. Refusal to sign informed consent form.
  11. Inability to comply with study visits and inspections.
  12. Psychiatric disorders that could interfere with the consent, participation or monitoring of the study.
  13. Fungal Systemic disease, bacterial, viral or other uncontrolled infection (defined as manifestation of signs / symptoms related to ongoing infection and without improvement, although receiving adequate antibiotic therapy or other treatment).
  14. Any other concomitant serious disease or a history of severe organ dysfunction or heart, kidney, liver or other organ system which may involve the patient in excessive risk when exposed to clofarabine.

  15. Diagnosis of another malignancy neoplasia, unless the patient has been disease-free for at least five years after completing an attempt curative therapy with the following exceptions:

    • Patients with non-melanoma skin cancer, carcinoma in situ or cervical intraepithelial neoplasia, irrespective of the duration of disease-free period, are eligible for the study if it has finalized a definitive treatment for the disease.
    • Patients with prostate cancer confined to the organ without evidence of recurrent or progressive disease based on figures for the prostate specific antigen (PSA) are also candidates for the study if hormonal therapy has been initiated or has made a radical prostatectomy.
  16. Clinical evidence which may indicate central nervous system (CNS) leukemia unless lumbar puncture to confirm the absence of leukemic blasts in the cerebrospinal fluid (CSF).
  17. Previous positive test for human immunodeficiency virus (HIV).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Clofarabine-Cytarabine
Induction therapy with a combination of clofarabine and low-dose cytarabine followed by consolidation therapy with clofarabine and low-dose cytarabine
Drug: Clofarabine
Drug: Cytarabine

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Efficacy
Time Frame: 1 year
Evaluate the efficacy in terms of complete responses of induction therapy and first-line consolidation of Clofarabine and low-dose Cytarabine with AML patients aged 60 years or more. The first efficacy objective is evaluate the overall remission rate (TRG), where general reference (RG) is defined as a patient who achieved complete remission (CR) or complete remission with inadequate platelet recovery (CPR).
1 year

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
To evaluate disease-free survival (DFS)
Evaluate the overall survival (OS)
To evaluate the safety
To assess the rate of mortality at 30 days
• The incidence, intensity (according to the latest version of the CTCAE classification), duration, causality, severity and type of AE

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
PETHEMA Foundation

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2010

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2012

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2012

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 31, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 31, 2010

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 1, 2010

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 7, 2014

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 4, 2014

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • AML-CLOFARA-CA09
  • 2010-019718-25 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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