Clofarabine and Gemtuzumab in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

October 7, 2015 updated by: UNC Lineberger Comprehensive Cancer Center

A Nonrandomized Dose-escalation Study of Clofarabine in Combination With Gemtuzumab Ozogamicin for Relapsed/Refractory Acute Myeloid Leukemia (AML) for Patients Less Than 60 Years-old

RATIONALE: Drugs used in chemotherapy, such as clofarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as gemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving clofarabine together with gemtuzumab may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of clofarabine when given together with gemtuzumab in treating patients with relapsed or refractory acute myeloid leukemia.

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

OBJECTIVES:

Primary

  • Identify the maximum tolerated dose and dose-limiting toxicities of clofarabine when administered with gemtuzumab ozogamicin in patients with refractory acute myeloid leukemia (AML) or with AML that has relapsed within 1 year after cytarabine-containing therapy.

Secondary

  • Estimate the rates of complete response and/or partial complete response with incomplete platelet recovery in patients treated with this regimen.
  • Estimate the duration of remission in patients treated with this regimen and not proceeding to high-dose therapy and allogeneic stem cell transplantation.
  • Estimate the frequency with which patients enrolled on this study proceed to allogeneic or autologous blood or bone marrow stem cell transplantation.

OUTLINE: This is a dose-escalation study of clofarabine.

Patients receive induction therapy comprising clofarabine IV on days 1-5 and gemtuzumab ozogamicin IV over 2 hours on days 1, 4, and 7 during course 1 only. Beginning in course 2, after blood counts recover, patients receive consolidation therapy comprising clofarabine IV on days 1-5. Consolidation treatment repeats upon blood count recovery for up to 2 courses in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients in remission after consolidation therapy are followed monthly for the first 6 months, and then every 3-4 months for 2 years.

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 (Actual)

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.
21

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 1

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

  • United States
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599-7295
        • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

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

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Diagnosis of acute myeloid leukemia (AML) meeting 1 of the following criteria:

    • Refractory disease, defined as persistent or progressive disease after ≥ 2 induction regimens, including ≥ 1 course of high-dose cytarabine (ARA-C)
    • Relapsed disease that has recurred within 1 year of an ARA-C-containing chemotherapy regimen

  • No CNS disease requiring radiotherapy

    • Patients with neurological symptoms must undergo a lumbar puncture and a CT scan or MRI of the brain to exclude brain metastasis

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Total bilirubin ≤ 2.0 times upper limit of normal (ULN)
  • ALT and AST ≤ 2.0 times the ULN
  • Serum creatinine ≤ 1.0 mg/dL OR glomerular filtration rate > 60 mL/min

  • INR ≤ 1.5 and aPTT within ULN

    • Patients receiving anticoagulation therapy (e.g., warfarin or heparin) are eligible provided anticoagulation therapy can be discontinued or changed to parenteral medications while the platelet count is less than 50,000/mm³
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No concurrent active second primary malignancy (excluding superficial, non-invasive skin cancers)
  • No active bleeding diathesis, not including closely monitored therapeutic anticoagulation

  • No cardiac disease, including any of the following:

    • New York Heart Association class II-IV congestive heart failure
    • Unstable angina (i.e., anginal symptoms at rest)
    • New onset angina (i.e., began within the past 3 months)
    • Myocardial infarction within the past 6 months
  • No active clinically serious infection > grade 2
  • No cerebrovascular accident, including transient ischemic attacks, within the past 6 months
  • No pulmonary hemorrhage ≥ grade 2 within the past 4 weeks
  • No other hemorrhage or bleeding event ≥ grade 3 within the past 4 weeks
  • No known HIV infection or chronic hepatitis B or C
  • No serious non-healing wound or ulcer
  • More than 4 weeks since prior significant traumatic injury
  • No prior history of sinusoidal obstructive syndrome (veno-occlusive disease)

PRIOR CONCURRENT THERAPY:

  • More than 4 weeks since prior major surgery or open biopsy
  • More than 100 days since any prior hematopoietic stem cell transplant

  • No concurrent treatment with any other investigational agent for AML

    • Intrathecal chemotherapy administration is allow for central nervous system leukemic infiltration
  • No prior allogeneic stem cell transplant within the past 100 days, with active graft-versus-host disease (GVHD) of any grade, or exposure to immynosuppression for GVHD or prophylaxis

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: N/A
  • 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.
Other: single arm study
1
Drug: clofarabine
Intravenous, 20mg/m2, Days 1, 2, 3, 4 and 5; 2 cycles
Other Names:
  • Clolar
Drug: gemtuzumab ozogamicin
Intravenous, 3mg/m2, Day 1, one cycle
Other Names:
  • Mylotarg

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
Time Frame
Maximum tolerated dose of clofarabine
Time Frame: 3 years
3 years

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
Time Frame
Rate of complete response and/or partial complete response with incomplete platelet recovery
Time Frame: 3 years
3 years
Duration of remission
Time Frame: 5 years
5 years
Frequency of patients proceeding to allogeneic or autologous blood or bone marrow stem cell transplantation
Time Frame: 5 years
5 years

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.
UNC Lineberger Comprehensive Cancer Center

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.
National Cancer Institute (NCI)
Genzyme, a Sanofi Company

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Thomas C. Shea, MD, UNC Lineberger Comprehensive Cancer Center

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.
November 1, 2007

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.
July 1, 2010

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.
August 1, 2015

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).
December 19, 2007

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.
December 19, 2007

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.
December 20, 2007

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.
October 12, 2015

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.
October 7, 2015

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.
October 1, 2015

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.
  • LCCC 0708
  • P30CA016086 (U.S. NIH Grant/Contract)
  • CDR0000580801 (Other Identifier: PDQ number)
  • UNC-LCCC-07-1222

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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