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S0333 Combination Chemotherap...

S0333 Combination Chemotherapy in Treating Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

Last Updated: 2015-03-25

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

79 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-04-30

Study Completion Date

2014-11-30

Brief Summary

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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), and giving the drugs in different combinations may kill more cancer cells.

PURPOSE: This phase II trial is studying how well combination chemotherapy works in treating patients with newly diagnosed acute lymphoblastic leukemia.

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Detailed Description

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OBJECTIVES:

Primary

* Determine the probability of 1-year continuous complete remission in patients with newly diagnosed acute lymphoblastic leukemia treated with first induction chemotherapy comprising daunorubicin, vincristine, prednisone, and pegaspargase; and second induction chemotherapy comprising high-dose cytarabine and mitoxantrone.

Secondary

* Determine the frequency and severity of toxic effects of these induction regimens followed by consolidation therapy comprising cyclophosphamide, cytarabine, mercaptopurine, and methotrexate and maintenance chemotherapy comprising mercaptopurine, methotrexate, vincristine, doxorubicin, dexamethasone, cyclophosphamide, thioguanine, and cytarabine in these patients.

Other objectives (if funding allows):

* To evaluate in a preliminary manner the significance of detecting minimal residual disease as a prognostic factor for survival and relapse-free survival of patients receiving chemotherapy
* To evaluate in a preliminary manner the pattern of gene expression of patients entered onto the trial and its relationship to cytogenetics/FISH risk classification, overall survival, and relapse-free survival

OUTLINE: This is a multicenter study.

* First induction chemotherapy: Patients receive daunorubicin IV on days 1-3; vincristine IV on days 1, 8, 15, and 22; prednisone IV or orally on days 1-28, followed by a taper to day 35; and pegaspargase IV or subcutaneously (SC) on day 15. Patients with CNS leukemia also receive methotrexate intrathecally (IT) or intraventricularly twice weekly and oral leucovorin calcium four times daily for 4 doses after each administration of methotrexate. When blasts are no longer present in the spinal fluid, patients receive methotrexate IT or intraventricularly once weekly for 4 weeks and then once monthly for 1 year.

Patients are reevaluated on day 28. Patients who achieve A1 bone marrow status and B1 peripheral blood status or those with resistant disease proceed to second induction therapy.

* Second induction chemotherapy: Patients receive high-dose cytarabine IV on days 1-5; mitoxantrone IV on day 3; and filgrastim (G-CSF) SC or IV beginning on day 7 and continuing until blood counts recover. Patients with CNS leukemia also receive methotrexate and leucovorin calcium as in first induction chemotherapy.

Patients are reevaluated on day 28. Patients who achieve A1 bone marrow status and B1 peripheral blood status with no extramedullary disease (other than CNS involvement) proceed to consolidation chemotherapy. Patients with resistant disease OR Philadelphia chromosome- or BCR/ABL-positive disease are removed from the study after receiving double induction chemotherapy.

* Consolidation chemotherapy: Patients receive cyclophosphamide IV on days 1, 15, and 29; cytarabine IV on days 2-5 and 16-19; oral mercaptopurine on days 1-28; and methotrexate IT or intraventricularly on days 2, 9, 16, and 23. Patients with CNS leukemia also undergo cranial radiotherapy once daily, 5 days a week, for 2 weeks.

Patients in complete remission proceed to maintenance chemotherapy.

* Maintenance chemotherapy:

* Course 1: Patients receive oral mercaptopurine on days 1-63 and oral methotrexate on days 1, 8, 15, 22, 29, 36, 43, 50, and 57. Patients proceed to course 2 after blood counts recover.
* Course 2: Patients receive vincristine IV and doxorubicin IV on days 1, 8, 15, and 22 and oral dexamethasone on days 1-28. Patients proceed to course 3 after blood counts recover.
* Course 3: Patients receive cyclophosphamide IV on day 1; oral thioguanine on days 1-14; and cytarabine IV on days 3-6 and 10-13. Patients proceed to course 4 after blood counts recover.
* Course 4: Patients receive oral mercaptopurine once daily for 2 years and oral methotrexate once weekly for 2 years.

Treatment continues in the absence of disease relapse or unacceptable toxicity.

After completion of study therapy, patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually for 3 years.

Conditions

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Leukemia

Study Design

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Allocation Method

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Induc x2, Consol, Maint

Induc 1: Allopurinol; Daunorubicin; Vincristine; Prednisone; asparaginase; Bactrim Induc 2: Allopurinol; cytarabine; Dexamethasone; filgrastim; mitoxantrone; Methotrexate; leucovorin Consol: Cyclophosphamide; cytarabine; 6-mercaptopurine; Methotrexate; filgrastim Maint:Course 1: 6-mercaptopurine; Methotrexate Course 2: Vincristine; doxorubicin; Dexamethasone Course 3: Cyclophosphamidee; thioguanine; cytarabine Course 4: 6-mercaptopurine; methotrexate

Group Type EXPERIMENTAL

filgrastim

Intervention Type BIOLOGICAL

As needed per physician discretion

cyclophosphamide

Intervention Type DRUG

Cyclophosphamide Consolidation: 650 mg/m2; IV; days 1, 15, 29 Post-consolidation course 3: 650 mg/m2; IV; day 1

cytarabine

Intervention Type DRUG

Induction 2: 3 g/m2; IV over 3 hrs; days 1-5 Consolidation: 75 mg/m2/d; IV push; days 2-5 and 16-19 Post-consolidation course 3: 75 mg/m2/d; IV push; days 3-6 and 10-13

daunorubicin

Intervention Type DRUG

Induction: 60 mg/m2/d; IV; days 1, 2, and 3

dexamethasone

Intervention Type DRUG

Induction 2: 0.1% QID; eye drops; days 1-6 Post consolidation course 2: 10 mg/m2/d; PO; days 1-28

doxorubicin

Intervention Type DRUG

Post consolidation: 25 mg/m2; IV; days 1, 8, 15, and 22

leucovorin

Intervention Type DRUG

For CNS during induction: 5 mg every 6 hrs for 4 doses; PO; days 1, 4, 8, 11, etx.; after methotrexate if WBC \< 3,000

mercaptopurine

Intervention Type DRUG

Consolidation: 60 mg/m2; PO; days 1-28 Post-consolidation course 1: 60 mg/m2/d; PO; days 1-63 Post-consolidation course 4: 60 mg/m2/d; PO; daily for 2 yrs

methotrexate

Intervention Type DRUG

Consolidation: 12 mg; intrathecal or intraventricularly; days 2, 9, 16, and 23 Post-consolidation course 1: 20 mg/m2/wk; PO; days 1, 8 15, 22, 29, 36, 43, 50, 57 Post-consolidation course 4: 20 mg/m2; PO; weekly for 2 yrs

mitoxantrone

Intervention Type DRUG

Induction 2: 80 mg/m2; IV; day 3

Asparaginase

Intervention Type DRUG

Induction: 2,000 IU/m2; IM or IV; day 15

prednisone

Intervention Type DRUG

Induction: 60 mg/m2/d; PO or IV; days 1-35

thioguanine

Intervention Type DRUG

Post-consolidation course 3: 60 mg/m2/d; PO; days 1-14

vincristine

Intervention Type DRUG

Induction: 1.4 mg/m2/d (2 mg max); IV; days 1, 8, 15, 22

radiation therapy

Intervention Type RADIATION

For CNS during consolidation: cranial radiation after blasts are no longer present in spinal fluid. Total dose of 1800 cGy over 2 wks in 10 fractions of 180 cGy 5 days/wk.

allopurinol

Intervention Type DRUG

300 mg/d PO Days 1-7

bactrim

Intervention Type DRUG

1 double strenth tablet 2x/d, 2x/wk, PO, begin with prednisone

Interventions

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filgrastim

As needed per physician discretion

Intervention Type BIOLOGICAL

cyclophosphamide

Cyclophosphamide Consolidation: 650 mg/m2; IV; days 1, 15, 29 Post-consolidation course 3: 650 mg/m2; IV; day 1

Intervention Type DRUG

cytarabine

Induction 2: 3 g/m2; IV over 3 hrs; days 1-5 Consolidation: 75 mg/m2/d; IV push; days 2-5 and 16-19 Post-consolidation course 3: 75 mg/m2/d; IV push; days 3-6 and 10-13

Intervention Type DRUG

daunorubicin

Induction: 60 mg/m2/d; IV; days 1, 2, and 3

Intervention Type DRUG

dexamethasone

Induction 2: 0.1% QID; eye drops; days 1-6 Post consolidation course 2: 10 mg/m2/d; PO; days 1-28

Intervention Type DRUG

doxorubicin

Post consolidation: 25 mg/m2; IV; days 1, 8, 15, and 22

Intervention Type DRUG

leucovorin

For CNS during induction: 5 mg every 6 hrs for 4 doses; PO; days 1, 4, 8, 11, etx.; after methotrexate if WBC \< 3,000

Intervention Type DRUG

mercaptopurine

Consolidation: 60 mg/m2; PO; days 1-28 Post-consolidation course 1: 60 mg/m2/d; PO; days 1-63 Post-consolidation course 4: 60 mg/m2/d; PO; daily for 2 yrs

Intervention Type DRUG

methotrexate

Intervention Type DRUG

mitoxantrone

Induction 2: 80 mg/m2; IV; day 3

Intervention Type DRUG

Asparaginase

Induction: 2,000 IU/m2; IM or IV; day 15

Intervention Type DRUG

prednisone

Induction: 60 mg/m2/d; PO or IV; days 1-35

Intervention Type DRUG

thioguanine

Post-consolidation course 3: 60 mg/m2/d; PO; days 1-14

Intervention Type DRUG

vincristine

Induction: 1.4 mg/m2/d (2 mg max); IV; days 1, 8, 15, 22

Intervention Type DRUG

radiation therapy

For CNS during consolidation: cranial radiation after blasts are no longer present in spinal fluid. Total dose of 1800 cGy over 2 wks in 10 fractions of 180 cGy 5 days/wk.

Intervention Type RADIATION

allopurinol

300 mg/d PO Days 1-7

Intervention Type DRUG

bactrim

1 double strenth tablet 2x/d, 2x/wk, PO, begin with prednisone

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* FAB class L3 ALL
* Non-Hodgkin's lymphoma
* Chronic myelogenous leukemia in lymphoid blast crisis
* Mixed lineage acute myeloid leukemia
* Acute minimally differentiated myeloid leukemia (M0)
* Must be registered on protocols SWOG-9007 AND SWOG-S9910

PATIENT CHARACTERISTICS:

Age

* 18 to 64

Performance status

* Zubrod 0-3

Life expectancy

* Not specified

Hematopoietic

* Not specified

Hepatic

* No chronic liver disease
* Hepatitis panel, including hepatitis B and C, negative

* History of hepatitis A with positive antibody allowed

Renal

* Creatinine ≤ 1.5 times upper limit of normal OR
* Creatinine clearance \> 60 mL/min

Cardiovascular

* Left ventricular function normal

* Ejection fraction ≥ 50% by MUGA or 2-dimensional echocardiogram
* No symptomatic congestive heart failure
* No coronary artery disease
* No cardiomyopathy
* No uncontrolled arrhythmia

Other

* Not pregnant or nursing
* Fertile patients must use effective contraception
* HIV negative
* No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* No prior remission induction chemotherapy for ALL

* Prior hydroxyurea to control WBC count allowed

Endocrine therapy

* Not specified

Radiotherapy

* Not specified

Surgery

* Not specified

Other

* No other prior treatment for ALL

Minimum Eligible Age

18 Years

Maximum Eligible Age

64 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jerry Radich, MD

Role: STUDY_CHAIR

Fred Hutchinson Cancer Center

Frederick R. Appelbaum, MD

Role: PRINCIPAL_INVESTIGATOR

Fred Hutchinson Cancer Center

Locations

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Providence Saint Joseph Medical Center - Burbank

Burbank, California, United States

Site Status

Cardinal Bernardin Cancer Center at Loyola University Medical Center

Maywood, Illinois, United States

Site Status

Cancer Center of Kansas, PA - Chanute

Chanute, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Dodge City

Dodge City, Kansas, United States

Site Status

Cancer Center of Kansas, PA - El Dorado

El Dorado, Kansas, United States

Site Status

Cancer Center of Kansas-Independence

Independence, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Kingman

Kingman, Kansas, United States

Site Status

Lawrence Memorial Hospital

Lawrence, Kansas, United States

Site Status

Southwest Medical Center

Liberal, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Newton

Newton, Kansas, United States

Site Status

Menorah Medical Center

Overland Park, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Parsons

Parsons, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Pratt

Pratt, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Salina

Salina, Kansas, United States

Site Status

Shawnee Mission Medical Center

Shawnee Mission, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Wellington

Wellington, Kansas, United States

Site Status

Associates in Womens Health, PA - North Review

Wichita, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Medical Arts Tower

Wichita, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Wichita

Wichita, Kansas, United States

Site Status

CCOP - Wichita

Wichita, Kansas, United States

Site Status

Via Christi Cancer Center at Via Christi Regional Medical Center

Wichita, Kansas, United States

Site Status

Wesley Medical Center

Wichita, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Winfield

Winfield, Kansas, United States

Site Status

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Site Status

Josephine Ford Cancer Center at Henry Ford Hospital

Detroit, Michigan, United States

Site Status