CINJALL: Treatment for Children With Acute Lymphocytic Leukemia

The purpose of this research study is to identify better ways to treat children and young adults with acute lymphocytic leukemia (ALL). At the same time, doctors hope to define methods to identify those patients at higher risk for certain side effects, as well as those who are at higher risk for relapse of their leukemia.

Study Overview

• Status: Completed
• Conditions: Acute Lymphocytic Leukemia
• Intervention / Treatment: Drug: Leucovorin; Drug: L-asparaginase; Drug: daunomycin; Drug: dexamethasone; Drug: 6-mercaptopurine; Drug: methotrexate; Drug: vincristine; Drug: Triple Intrathecal Therapy (MTX, Cytarabine, Hydrocortisone); Drug: aminopterin; Drug: cyclophosphamide; Drug: cytarabine; Drug: 6-thioguanine

Detailed Description

Outline of Therapy:

Combinations of chemotherapy drugs will be given orally, intravenously and intrathecally (directly into the cerebrospinal fluid by spinal tap) over a period of roughly two and a half years.

Therapy will be divided into five phases:

Induction (4 weeks): chemotherapy given to produce a clinical remission (defined by normal blood counts, with the absence of leukemia cells in the blood and fewer than 5% leukemia cells in the bone marrow).

Consolidation (11 weeks): chemotherapy given to consolidate the remission. Delayed Intensification (7 weeks) Intensive chemotherapy aimed at killing any resistant leukemia cells will be given only for patients at high risk of relapse.

Intensive Continuation (approximately 1 year): Eight week cycles of chemotherapy, given eight times.

Continuation (final year of therapy): Eight week cycles of largely oral chemotherapy, with one clinic visit for a lumbar puncture every eight weeks.

Irradiation: radiation will be given in the middle of intensive continuation to the head and spine of those patients who have leukemia cells found in the cerebrospinal fluid at the time of diagnosis.

Follow-up: After the conclusion of therapy, there will be periodic office visits, initially monthly, then gradually spaced out to annual visits. The purpose of these visits is to evaluate for late side-effects of therapy.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Neptune, New Jersey, United States, 07754
      • Jersey Shore University Medical Center
    • New Brunswick, New Jersey, United States, 08903
      • Cancer Institute of New Jersey

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 30 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion:

• Newly Diagnosed ALL, excluding mature B-cell ALL (surface Ig positive)
• Patients with overt CNS (central nervous system) or testicular disease are eligible
• Informed consent according to institutional and FDA guidelines.
• Adequate organ function is required.
• HIV seropositive patients will not be excluded from this study.
• Patients greater than 1 year of age and less than 29.99 years of age are eligible.

Exclusion Criteria

• Patients with medical, psychological, or psychiatric problems that are likely to compromise their ability to tolerate intensive therapy will be ineligible.
• All patients with evidence of significant organ dysfunction not thought to be attributable to ALL (patients with clinically significant congestive heart failure, cardiac ejection fraction <40%, total bilirubin >2, serum creatinine >2) will be ineligible. Note: echocardiogram or MUGA are required prior to therapy ONLY for those patients with history or physical findings suggestive of cardiac dysfunction not directly attributable to anemia or ALL. Note: Patients with total bilirubin >2 but direct (conjugated) bilirubin less than the upper limit of normal will still be eligible. These patients should be evaluated for deficiency of the enzyme glucuronyl transferase.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Arm 1 Standard Risk; 6-MERCAPTOPURINE DAUNOMYCIN DEXAMETHASONE Triple Intrathecal Therapy (ITT) L-ASPARAGINASE VINCRISTINE METHOTREXATE Leucovorin	Drug: Leucovorin; Drug: L-asparaginase; Therapy will be divided into five phases: Induction, Consolidation, Delayed Intensification (only for those patients meeting clinical criteria defining a high risk of relapse), Intensive Continuation, and Continuation; Drug: daunomycin; Therapy will be divided into five phases: Induction, Consolidation, Delayed Intensification (only for those patients meeting clinical criteria defining a high risk of relapse), Intensive Continuation, and Continuation; Drug: dexamethasone; Therapy will be divided into five phases: Induction, Consolidation, Delayed Intensification (only for those patients meeting clinical criteria defining a high risk of relapse), Intensive Continuation, and Continuation; Drug: 6-mercaptopurine; Therapy will be divided into five phases: Induction, Consolidation, Delayed Intensification (only for those patients meeting clinical criteria defining a high risk of relapse), Intensive Continuation, and Continuation; Drug: methotrexate; Therapy will be divided into five phases: Induction, Consolidation, Delayed Intensification (only for those patients meeting clinical criteria defining a high risk of relapse), Intensive Continuation, and Continuation; Drug: vincristine; Therapy will be divided into five phases: Induction, Consolidation, Delayed Intensification (only for those patients meeting clinical criteria defining a high risk of relapse), Intensive Continuation, and Continuation; Drug: Triple Intrathecal Therapy (MTX, Cytarabine, Hydrocortisone)
EXPERIMENTAL: Arm 2 High Risk; 6-MERCAPTOPURINE DAUNOMYCIN DEXAMETHASONE Triple Intrathecal Therapy (ITT) L-ASPARAGINASE VINCRISTINE 6-THIOGUANINE CYTARABINE AMINOPTERIN CYCLOPHOSPHAMIDE ARABINOSIDE-C	Drug: Leucovorin; Drug: L-asparaginase; Therapy will be divided into five phases: Induction, Consolidation, Delayed Intensification (only for those patients meeting clinical criteria defining a high risk of relapse), Intensive Continuation, and Continuation; Drug: daunomycin; Therapy will be divided into five phases: Induction, Consolidation, Delayed Intensification (only for those patients meeting clinical criteria defining a high risk of relapse), Intensive Continuation, and Continuation; Drug: dexamethasone; Therapy will be divided into five phases: Induction, Consolidation, Delayed Intensification (only for those patients meeting clinical criteria defining a high risk of relapse), Intensive Continuation, and Continuation; Drug: 6-mercaptopurine; Therapy will be divided into five phases: Induction, Consolidation, Delayed Intensification (only for those patients meeting clinical criteria defining a high risk of relapse), Intensive Continuation, and Continuation; Drug: vincristine; Therapy will be divided into five phases: Induction, Consolidation, Delayed Intensification (only for those patients meeting clinical criteria defining a high risk of relapse), Intensive Continuation, and Continuation; Drug: Triple Intrathecal Therapy (MTX, Cytarabine, Hydrocortisone); Drug: aminopterin; Therapy will be divided into five phases: Induction, Consolidation, Delayed Intensification (only for those patients meeting clinical criteria defining a high risk of relapse), Intensive Continuation, and Continuation; Drug: cyclophosphamide; Therapy will be divided into five phases: Induction, Consolidation, Delayed Intensification (only for those patients meeting clinical criteria defining a high risk of relapse), Intensive Continuation, and Continuation; Drug: cytarabine; Therapy will be divided into five phases: Induction, Consolidation, Delayed Intensification (only for those patients meeting clinical criteria defining a high risk of relapse), Intensive Continuation, and Continuation; Drug: 6-thioguanine; Therapy will be divided into five phases: Induction, Consolidation, Delayed Intensification (only for those patients meeting clinical criteria defining a high risk of relapse), Intensive Continuation, and Continuation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients With ALL at High Risk of Relapse (Arm 2) Who Were Relapse-free at 5 Years	This measure looks at the percentage of patients on Arm 2 who did not experience a relapse at 5 years, where relapse is defined as the presence of progressive disease after the achievement of a complete remission.	5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
To Measure 5-methyltetrahydrofolate, Aminopterin and Methotrexate Uptake in Leukemic Blasts Isolated at Diagnosis	5 years

Collaborators and Investigators

• Sponsor: Rutgers, The State University of New Jersey
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Barton Kamen, MD, Rutgers, the State University of New Jersey

Study record dates

Study Major Dates

• Study Start: February 1, 2001
• Primary Completion (ACTUAL): September 1, 2008
• Study Completion (ACTUAL): September 1, 2008

Study Registration Dates

• First Submitted: September 12, 2005
• First Submitted That Met QC Criteria: September 12, 2005
• First Posted (ESTIMATE): September 15, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): June 9, 2014
• Last Update Submitted That Met QC Criteria: May 12, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: Leukemia; Acute Lymphocytic Leukemia
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protective Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Dermatologic Agents; Micronutrients; Antibiotics, Antineoplastic; Vitamins; Reproductive Control Agents; Antidotes; Vitamin B Complex; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Dexamethasone; Cyclophosphamide; Leucovorin; Cytarabine; Methotrexate; Vincristine; Daunorubicin; Asparaginase; Mercaptopurine; Aminopterin; Hydrocortisone; Thioguanine
• Other Study ID Numbers: 020101; P30CA072720 (U.S. NIH Grant/Contract); 0220003389 (OTHER: IRB Number)