Combination Chemotherapy in Treating Patients With Untreated Acute Lymphoblastic Leukemia

NCT ID: NCT00003700

Last Updated: 2016-07-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

163 participants

Study Classification

INTERVENTIONAL

Study Start Date

1999-01-31

Study Completion Date

2010-01-31

Brief Summary

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RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy in treating patients who have untreated acute lymphoblastic leukemia.

Detailed Description

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OBJECTIVES:

* Determine the complete response rate and toxicity of escalating doses of daunorubicin in patients under 60 years old with untreated acute lymphoblastic leukemia (ALL).
* Determine the complete response rate and toxicity of a constant dose of daunorubicin in patients at least 60 years old with untreated ALL.
* Determine the toxicity of high dose cytarabine during postremission therapy in these patients.
* Determine the CNS relapse rate of ALL when prophylactic intrathecal methotrexate and high-dose intravenous chemotherapy replace cranial irradiation.

OUTLINE:

* Course I: Patients are assigned to 1 of 2 induction treatment groups based on age.

* Group 1 (under age 60): Patients receive cyclophosphamide IV over 15-30 minutes on day 1, escalating doses of daunorubicin IV over 5-10 minutes on days 1-3, vincristine IV on days 1, 8, 15, and 22, oral prednisone on days 1-21, asparaginase intramuscularly on days 5, 8, 11, 15, 18, and 22, and filgrastim (G-CSF) subcutaneously (SC) beginning on day 4 and continuing for at least 7 days and then until blood counts recover.
* Group 2 (age 60 and over): Patients receive vincristine, asparaginase, cyclophosphamide, and G-CSF as in group 1, fixed dose daunorubicin IV over 5-10 minutes on days 1-3, and oral prednisone on days 1-7.

Patients are then evaluated for bone marrow cellularity on day 29. Those with M0, M1, or M2 cellularity proceed to course II. Patients with M3 cellularity may proceed to course II or be removed from study.

* Course II (early intensification): Patients receive intrathecal methotrexate and cyclophosphamide IV over 15-30 minutes on day 1, cytarabine IV over 3 hours on days 1-3, and G-CSF SC beginning on day 4.

Bone marrow is again examined on day 29. Patients with M0 or M1 cellularity after course I and no sign of relapse after course II proceed to course III. Patients with M2 or M3 cellularity after course I must have M0 or M1 cellularity after course II to proceed to course III. Patients with M2 or M3 cellularity after course II are removed from study.

* Course III: Patients receive intrathecal methotrexate, vincristine IV, and methotrexate IV over 3 hours on days 1, 8, and 15 and oral methotrexate every 6 hours for 4 doses beginning 6 hours after starting methotrexate IV on days 1, 2, 8, 9, 15, and 16. Patients receive leucovorin calcium IV 6 hours after the last oral methotrexate dose on days 2, 9, and 16 and oral leucovorin calcium beginning 12 hours after leucovorin calcium IV for at least 4 doses on days 3, 4, 10, 11, 17, and 18.

Patients must be off leucovorin calcium for a minimum of 3 days before beginning days 8 and 15 of treatment. Patients who maintain M0 or M1 cellularity on day 29 of course III continue therapy. Those with M2 or M3 cellularity after course III are removed from the study.

* Course IV (Late intensification): Repeat course I.
* Course V (Late intensification): Repeat course II.
* Course VI (CNS intensification): Repeat course III.
* Course VII (Prolonged maintenance): Patients receive oral mercaptopurine daily, vincristine IV once every 4 weeks, oral prednisone on days 1-5, and oral methotrexate on days 1, 8, 15, and 22. Courses repeat every 4 weeks for up to 18 months.

Patients with testicular disease receive gonadal radiotherapy anytime after course I. Chemotherapy is not halted during radiotherapy.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually for 10 years.

PROJECTED ACCRUAL: A total of 140 patients will be accrued for this study within 15 months.

Conditions

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Leukemia

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Daunorubicin, ara-C, & MTX Therapy

daunorubicin during induction, increasing doses of cytarabine during consolidation followed by methotrexate in place of cranial irradiation for treatment of ALL

Group Type EXPERIMENTAL

G-CSF

Intervention Type BIOLOGICAL

Courses I, II, IV, V: 5 ug/kg/d subQ injection Day 4 until ANC \> 5,000 uL after nadir: 7 day minimum for Courses I \& IV

asparaginase

Intervention Type DRUG

6000 U/sq m subQ or IM injection 2X/wk for 6 doses starting on Day 5: Courses I \& IV

cyclophosphamide

Intervention Type DRUG

1200 mg/sq m IV infusion over 15-30 min Day 1 Courses I \& IV (pts \< 60y/o) 1000 mg/sq m IV infusion over 15-30 min Day 1 Courses II \& V

cytarabine

Intervention Type DRUG

2000 mg/sq m IV infusion over 3 hrs Days 1,2, \& 3: Courses II \& V

daunorubicin hydrochloride

Intervention Type DRUG

80mg/sq m (pts\<60y/o)OR 60mg/sq m (pts =/\>60y/o) IV infusion over 5-10 min Days 1,2,\& 3: Courses I \& IV

leucovorin calcium

Intervention Type DRUG

Courses III \& VI:

25mg/sq m IV infusion Days 2, 9, and 16 5mg/sq m PO q 6 hr for 8 doses or until serum MTX \<0.05 uM after ea IV dose

mercaptopurine

Intervention Type DRUG

60mg/sq m/d PO every day Course VII

methotrexate

Intervention Type DRUG

15mg intrathecal Day 1 Courses II \& V 1000mg/sq m IV infusion over 3 hrs Days 1, 8, \& 15 and 25mg/sq m PO q 6hr x 4 doses after ea IV dose: Courses III \& VI.

prednisone

Intervention Type DRUG

60mg/sq m/day PO Days 1-21 (pts\<60y/o) OR Days 1-7 (pts \>/= 60y/o) Courses I \& IV and Days 1-5 of ea 4 cycle in Course VII

vincristine sulfate

Intervention Type DRUG

2 mg total IV infusion Days 1,8,15,\& 22 Courses I \& IV and Days 1, 8, \& 15 Courses III \& VI, and Day 1 of ea 4 wk cycle in Course VII

Allopurinol

Intervention Type DRUG

300mg PO q day Days 1-14 Course I

Interventions

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G-CSF

Courses I, II, IV, V: 5 ug/kg/d subQ injection Day 4 until ANC \> 5,000 uL after nadir: 7 day minimum for Courses I \& IV

Intervention Type BIOLOGICAL

asparaginase

6000 U/sq m subQ or IM injection 2X/wk for 6 doses starting on Day 5: Courses I \& IV

Intervention Type DRUG

cyclophosphamide

1200 mg/sq m IV infusion over 15-30 min Day 1 Courses I \& IV (pts \< 60y/o) 1000 mg/sq m IV infusion over 15-30 min Day 1 Courses II \& V

Intervention Type DRUG

cytarabine

2000 mg/sq m IV infusion over 3 hrs Days 1,2, \& 3: Courses II \& V

Intervention Type DRUG

daunorubicin hydrochloride

80mg/sq m (pts\<60y/o)OR 60mg/sq m (pts =/\>60y/o) IV infusion over 5-10 min Days 1,2,\& 3: Courses I \& IV

Intervention Type DRUG

leucovorin calcium

Courses III \& VI:

25mg/sq m IV infusion Days 2, 9, and 16 5mg/sq m PO q 6 hr for 8 doses or until serum MTX \<0.05 uM after ea IV dose

Intervention Type DRUG

mercaptopurine

60mg/sq m/d PO every day Course VII

Intervention Type DRUG

methotrexate

15mg intrathecal Day 1 Courses II \& V 1000mg/sq m IV infusion over 3 hrs Days 1, 8, \& 15 and 25mg/sq m PO q 6hr x 4 doses after ea IV dose: Courses III \& VI.

Intervention Type DRUG

prednisone

60mg/sq m/day PO Days 1-21 (pts\<60y/o) OR Days 1-7 (pts \>/= 60y/o) Courses I \& IV and Days 1-5 of ea 4 cycle in Course VII

Intervention Type DRUG

vincristine sulfate

2 mg total IV infusion Days 1,8,15,\& 22 Courses I \& IV and Days 1, 8, \& 15 Courses III \& VI, and Day 1 of ea 4 wk cycle in Course VII

Intervention Type DRUG

Allopurinol

300mg PO q day Days 1-14 Course I

Intervention Type DRUG

Other Intervention Names

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filgrastim ara-C

Eligibility Criteria

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Inclusion Criteria

1. Any other serious illnesses which would limit survival to \<2 years, or psychiatric condition which would prevent compliance with treatment or informed consent.
2. Uncontrolled or severe cardiovascular disease.
3. History of pancreatitis or overt coagulopathy (prior cerebrovascular accident or hemorrhage, transient ischemic attack or deep venous thrombosis).
4. Elevations in bilirubin, creatinine, or amylase that may suggest impaired hepatic, renal, or pancreatic function must be considered as potentially serious obstacles for safe tolerance of the therapy prescribed in this protocol.
5. Prior use of the agents administered in this protocol for other non-malignant disease may reduce the likelihood of beneficial outcome, and should also be considered prior to enrolling patients.
6. Treatment under this protocol would expose an unborn child to significant risks.

Women and men of reproductive potential should agree to use an effective means of birth control.
7. Unequivocal histologic diagnosis of Acute Lymphoblastic leukemia (ALL), FAB L1-or L2 or Acute Undifferentiated Leukemia (AUL).
8. Age ≥ 15 years
9. Prior Treatment: No prior treatment for leukemia, with three permissible exceptions:

i. emergency leukapheresis; ii. emergency treatment for hyperleukocytosis with hydroxyurea; iii. cranial RT for CNS leukostasis (one dose only).
Minimum Eligible Age

15 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Wendy Stock, MD

Role: STUDY_CHAIR

University of Chicago

Locations

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Veterans Affairs Medical Center - Birmingham

Birmingham, Alabama, United States

Site Status

University of California San Diego Cancer Center

La Jolla, California, United States

Site Status

UCSF Cancer Center and Cancer Research Institute

San Francisco, California, United States

Site Status

Veterans Affairs Medical Center - San Francisco

San Francisco, California, United States

Site Status

CCOP - Christiana Care Health Services

Wilmington, Delaware, United States

Site Status

Lombardi Cancer Center, Georgetown University

Washington D.C., District of Columbia, United States

Site Status

Walter Reed Army Medical Center

Washington D.C., District of Columbia, United States

Site Status

CCOP - Mount Sinai Medical Center

Miami Beach, Florida, United States

Site Status

University of Illinois at Chicago Health Sciences Center

Chicago, Illinois, United States

Site Status

Veterans Affairs Medical Center - Chicago (Westside Hospital)

Chicago, Illinois, United States

Site Status

University of Chicago Cancer Research Center

Chicago, Illinois, United States

Site Status

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status

Veterans Affairs Medical Center - Togus

Togus, Maine, United States

Site Status

Marlene & Stewart Greenebaum Cancer Center, University of Maryland

Baltimore, Maryland, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

University of Massachusetts Memorial Medical Center

Worcester, Massachusetts, United States

Site Status

Veterans Affairs Medical Center - Minneapolis

Minneapolis, Minnesota, United States

Site Status

Veterans Affairs Medical Center - Columbia (Truman Memorial)

Columbia, Missouri, United States

Site Status

Ellis Fischel Cancer Center - Columbia

Columbia, Missouri, United States

Site Status

Barnes-Jewish Hospital

St Louis, Missouri, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

CCOP - Southern Nevada Cancer Research Foundation

Las Vegas, Nevada, United States

Site Status

Norris Cotton Cancer Center

Lebanon, New Hampshire, United States

Site Status

Cooper Cancer Institute

Camden, New Jersey, United States

Site Status

St. Barnabas Medical Center

Livingston, New Jersey, United States

Site Status

St. Joseph's Hospital and Medical Center

Paterson, New Jersey, United States

Site Status

Veterans Affairs Medical Center - Buffalo

Buffalo, New York, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

CCOP - North Shore University Hospital

Manhasset, New York, United States

Site Status

North Shore University Hospital

Manhasset, New York, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

New York Presbyterian Hospital - Cornell Campus

New York, New York, United States

Site Status

Mount Sinai Medical Center, NY

New York, New York, United States

Site Status

CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.

Syracuse, New York, United States

Site Status

State University of New York - Upstate Medical University

Syracuse, New York, United States

Site Status

Veterans Affairs Medical Center - Syracuse

Syracuse, New York, United States

Site Status

Lineberger Comprehensive Cancer Center, UNC

Chapel Hill, North Carolina, United States

Site Status

Veterans Affairs Medical Center - Durham

Durham, North Carolina, United States

Site Status

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Site Status

CCOP - Southeast Cancer Control Consortium

Winston-Salem, North Carolina, United States

Site Status

Comprehensive Cancer Center of Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, United States

Site Status

Arthur G. James Cancer Hospital - Ohio State University

Columbus, Ohio, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

University of Tennessee, Memphis Cancer Center

Memphis, Tennessee, United States

Site Status

Veterans Affairs Medical Center - Memphis

Memphis, Tennessee, United States

Site Status

Vermont Cancer Center

Burlington, Vermont, United States

Site Status

Veterans Affairs Medical Center - White River Junction

White River Junction, Vermont, United States

Site Status

Veterans Affairs Medical Center - Richmond

Richmond, Virginia, United States

Site Status

MBCCOP - Massey Cancer Center

Richmond, Virginia, United States

Site Status

Countries

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United States

References

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Stock W, Yu D, Johnson J, et al.: Intensified Daunorubicin during induction and post-remission therapy of adult acute lymphoblastic leukemia (ALL): results of CALGB 19802. [Abstract] Blood 102 (11 Pt 1): A-1375, 2003.

Reference Type RESULT

Stock W, Dodge RK, Vardiman JW, et al.: Treatment of adult acute lymphoblastic leukemia (ALL): phase II trial of dose intensification of Daunorubicin and Cytarabine followed by high-dose Methotrexate and intrathecal Methotrexate in place of cranial irradiation (CALGB 19802). [Abstract] Blood 98 (11 Pt 1): A-2472, 2001.

Reference Type RESULT

Other Identifiers

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U10CA031946

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000066807

Identifier Type: REGISTRY

Identifier Source: secondary_id

CALGB-19802

Identifier Type: -

Identifier Source: org_study_id

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