Combination Chemotherapy in Treating Adult Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

January 9, 2014 updated by: Ohio State University Comprehensive Cancer Center

DFCI ALL Adult Consortium Protocol: Adult ALL Trial

RATIONALE: Drugs used in chemotherapy 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 phase II trial is studying the side effects of combination chemotherapy and to see how well it works in treating adult patients with newly diagnosed acute lymphoblastic leukemia.

Study Overview

Status

Status

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

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

  • To determine the feasibility, toxicity, and efficacy of a high-risk pediatric treatment regimen in adult patients with newly diagnosed acute lymphoblastic leukemia (ALL).
  • To explore the relative toxicity of pegaspargase IV.
  • To explore the relative efficacy and toxicity of adding imatinib mesylate to multi-agent chemotherapy for patients with Philadelphia chromosome-positive ALL.

Secondary

  • To estimate the complete remission (CR) rate at the end of induction therapy and calculate the corresponding 90% confidence interval (CI).
  • To estimate the disease-free survival (DFS), defined as the time from achieving a CR to the first disease recurrence or death, of a subset of patients who achieve a CR at the end of induction therapy.
  • To estimate the overall survival (OS), defined as the time from study entry to death from any cause, of all patients.
  • To calculate the median, 2-year, and 3-year DFS and OS rates and their corresponding 95% CI's.
  • To evaluate the prognostic significance of the prednisone prophase response, minimal residual disease at various time points, the frequency and type of tyrosine kinase mutations, and gene expression profiles at diagnosis.

OUTLINE: This is a multicenter study.

  • Steroid prophase therapy (for patients who have not received steroids within the past 7 days): Patients receive cytarabine intrathecally (IT) on day 0 or 1 and methylprednisolone IV 3 times daily on days 1-3.
  • Induction therapy (weeks 1-4): Patients receive vincristine sulfate IV on days 4, 11, 18, and 25; doxorubicin hydrochloride IV on days 4 and 5; methotrexate IV on day 6; pegaspargase IV over 1 hour on day 7; and prednisone or prednisolone orally 2-3 times daily or methylprednisolone IV 3 times daily on days 4-32. Patients also receive methotrexate, cytarabine, and hydrocortisone IT on day 18 and methotrexate IT on day 32. After completion of induction therapy, patients with documented complete remission (CR) proceed to consolidation IA therapy (group A). Patients with partial remission proceed to consolidation IC therapy (group B). Patients with refractory disease are removed from the study.

  • Consolidation I therapy (weeks 5-13): Patients are assigned to 1 of 2 groups according to their CR status.

    • Group A (patients who achieved CR by day 32 or patients with delayed recovery):

      • Consolidation IA therapy (weeks 5-7): Patients receive vincristine sulfate IV, doxorubicin hydrochloride IV, methotrexate IT, and high-dose methotrexate IV on day 1. Patients also receive oral mercaptopurine once daily on days 1-14. Patients then proceed to consolidation IB therapy.
      • Consolidation IB therapy (weeks 8-10): Patients receive cyclophosphamide IV over 1 hour and methotrexate IT on day 1, low-dose cytarabine IV or subcutaneously (SC) on days 2-5 and 9-12, and oral mercaptopurine once daily on days 1-14. Patients then proceed to consolidation IC therapy.
      • Consolidation IC therapy (weeks 11-13): Patients receive high-dose cytarabine IV over 3 hours twice daily on days 1 and 2, etoposide phosphate IV over 2 hours on days 3-5, and oral dexamethasone twice daily on days 1-5. Patients also receive pegaspargase IV over 1 hour every 2 weeks beginning on day 8 and continuing during CNS therapy and consolidation II therapy until a total of 15 doses are administered. After completion of consolidation IC therapy, patients proceed to CNS therapy.

    • Group B (patients who failed to enter a CR after 32 days of multi-agent induction chemotherapy):

      • Consolidation IC therapy (weeks 5-7): Patients receive high-dose cytarabine IV over 3 hours twice daily on days 1 and 2, etoposide phosphate IV over 2 hours on days 3-5, and oral dexamethasone twice daily on days 1-5. Patients who achieve CR at the end of consolidation IC therapy proceed to consolidation IA therapy. Patients with > 5% blast count at the end of consolidation IC therapy are removed from the study.
      • Consolidation IA therapy (weeks 8-10): Patients receive vincristine sulfate IV, doxorubicin hydrochloride IV, methotrexate IT, and high-dose methotrexate IV on day 1. Patients also receive oral mercaptopurine once daily on days 1-14. Patients then proceed to consolidation IB therapy.
      • Consolidation IB therapy (weeks 11-13): Patients receive cyclophosphamide IV over 1 hour and methotrexate IT on day 1, low-dose cytarabine IV or SC on days 2-5 and 9-12, and oral mercaptopurine once daily on days 1-14. Patients also receive pegaspargase IV over 1 hour every 2 weeks beginning on day 8 and continuing during CNS therapy and consolidation II therapy until a total of 15 doses are administered. After completion of consolidation IB therapy, patients proceed to CNS therapy.
  • CNS therapy (weeks 14-16): Patients receive vincristine sulfate IV and doxorubicin hydrochloride IV on day 1, oral mercaptopurine once daily on days 1-14, oral dexamethasone twice daily on days 1-5, and pegaspargase as described in consolidation I therapy. Patients also receive methotrexate, cytarabine, and hydrocortisone IT twice weekly for 4 doses and undergo cranial irradiation once daily for 8-10 days. After completion of CNS therapy, patients proceed to consolidation II therapy.
  • Consolidation II therapy (weeks 17-43): Patients receive vincristine sulfate IV and doxorubicin hydrochloride IV on day 1, oral mercaptopurine once daily on days 1-14, oral dexamethasone twice daily on days 1-5, and pegaspargase as described in consolidation I therapy. Treatment repeats every 3 weeks until patients have received a cumulative dosage of 300 mg/m^2 of doxorubicin hydrochloride and 30 post-remission weeks of pegaspargase have been administered. When patients complete doxorubicin hydrochloride, they receive methotrexate IV once weekly (except on the week that they receive methotrexate IT). Patients also receive methotrexate, cytarabine, and hydrocortisone IT every 18 weeks (first dose is given 18 weeks after the first lumbar puncture administered during CNS therapy). After completion of consolidation II therapy, patients proceed to continuation therapy.
  • Continuation therapy (weeks 44-113): Patients receive vincristine sulfate IV on day 1; methotrexate IV on days 1, 8, and 15; oral mercaptopurine once daily on days 1-14; and oral dexamethasone twice daily on days 1-5. Treatment repeats every 3 weeks for a total of 104 weeks (24 months) of continued CR. Patients also receive methotrexate, cytarabine, and hydrocortisone IT every 18 weeks. Patients do not receive methotrexate IV on the week that they receive methotrexate IT.

Patients with Philadelphia chromosome-positive disease or with bcr-abl translocation on molecular studies also receive oral imatinib mesylate once daily beginning on day 14 of induction therapy and continuing until completion of continuation therapy. These patients should proceed to allogeneic stem cell transplantation as soon as feasible based on donor availability and the patient's medical status.

Bone marrow, peripheral blood, and other samples are collected periodically for research studies (including minimal residual disease analysis, gene expression profiling, and tyrosine kinase sequencing).

After completion of study treatment, patients are followed up monthly for 6 months, every 2 months for 6 months, every 4 months for 1 year, every 6 months for 1 year, and then annually thereafter.

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.
180

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

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 50 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Diagnosis of acute lymphoblastic leukemia (ALL)

  • No known mature B-cell ALL*, defined by the presence of surface immunoglobulin, L3 morphology, t(8;14)(q24;q32), t(8;22), or t(2;8)

    • Patients with T-cell surface markers and t(8;14)(q24;q11) are eligible NOTE: *Patients with mature B-cell ALL will be removed from the study as soon as that diagnosis is made.
  • No secondary ALL (i.e., ALL arising after another malignancy)

PATIENT CHARACTERISTICS:

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No known HIV positivity (HIV testing is not required)
  • No comorbid medical condition that would, in the investigator's opinion, make participation in this study and adherence to the study guidelines a compromise to the study objectives
  • No active psychiatric or mental illness that would make giving informed consent or careful clinical follow-up unlikely

PRIOR CONCURRENT THERAPY:

  • No prior anti-leukemic therapy except ≤ 1 week of steroids, emergent radiotherapy to the mediastinum, hydroxyurea, or emergent leukapheresis

    • Patients who have received steroids within the past 7 days are eligible but will not receive steroid prophase therapy on study
  • No concurrent chronic steroids or anti-metabolite therapy

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
  • Masking: None (Open Label)

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
Toxicity
Feasibility of intensification therapy, measured as the percentage of patients who, having achieved a complete remission after induction therapy, receive > 25 weeks of pegaspargase IV as part of intensification therapy

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
Disease-free and overall survival
Complete remission rate
Prognostic significance of prednisone prophase response, minimal residual disease at various time points, tyrosine kinase mutations, and gene expression profiles at diagnosis

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.
Ohio State University 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)

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: William G. Blum, MD, Ohio State University 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.
January 1, 2009

Primary Completion (Anticipated)

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.
January 1, 2013

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).
October 30, 2009

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.
October 30, 2009

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.
November 1, 2009

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.
January 10, 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.
January 9, 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.
October 1, 2009

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.
  • CDR0000632144
  • OSU-08066
  • 2008C0112
  • DFCI-06254

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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