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

Leukemia Clinical Trial

Official title:

A Phase II Study of Double Induction Chemotherapy for Newly Diagnosed Non-L3 Adult Acute Lymphoblastic Leukemia With Investigation of Minimal Residual Disease and Risk of Relapse Following Maintenance Chemotherapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00109837
• Other study ID #: S0333
• Secondary ID: U10CA032102S0333
• Status: Completed
• Phase: Phase 2
• First received: May 3, 2005
• Last updated: March 5, 2015
• Start date: April 2005
• Est. completion date: November 2014

Study information

• Verified date: March 2015
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 79
• Est. completion date: November 2014
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 64 Years

Eligibility

DISEASE CHARACTERISTICS:

• Morphologically confirmed acute lymphoblastic leukemia (ALL), meeting any of the following criteria:

• FAB class L1 or L2 disease

• Mixed lineage ALL

• Ph-negative/BCR/ABL-negative

• Newly diagnosed disease

• Patients with the following diagnoses are not eligible:

• 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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Biological:
• filgrastim
As needed per physician discretion

Drug:
• cyclophosphamide
Cyclophosphamide Consolidation: 650 mg/m2; IV; days 1, 15, 29 Post-consolidation course 3: 650 mg/m2; IV; day 1
• 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
• daunorubicin
Induction: 60 mg/m2/d; IV; days 1, 2, and 3
• dexamethasone
Induction 2: 0.1% QID; eye drops; days 1-6 Post consolidation course 2: 10 mg/m2/d; PO; days 1-28
• doxorubicin
Post consolidation: 25 mg/m2; IV; days 1, 8, 15, and 22
• 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
• 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
• methotrexate
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
Induction 2: 80 mg/m2; IV; day 3
• Asparaginase
Induction: 2,000 IU/m2; IM or IV; day 15
• prednisone
Induction: 60 mg/m2/d; PO or IV; days 1-35
• thioguanine
Post-consolidation course 3: 60 mg/m2/d; PO; days 1-14
• vincristine
Induction: 1.4 mg/m2/d (2 mg max); IV; days 1, 8, 15, 22

Radiation:
• 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.

Drug:
• allopurinol
300 mg/d PO Days 1-7
• bactrim
1 double strenth tablet 2x/d, 2x/wk, PO, begin with prednisone

Locations

Country	Name	City	State
United States	AnMed Cancer Center	Anderson	South Carolina
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	St. Joseph Cancer Center	Bellingham	Washington
United States	Billings Clinic - Downtown	Billings	Montana
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana
United States	Northern Rockies Radiation Oncology Center	Billings	Montana
United States	St. Vincent Healthcare Cancer Care Services	Billings	Montana
United States	Bozeman Deaconess Cancer Center	Bozeman	Montana
United States	Olympic Hematology and Oncology	Bremerton	Washington
United States	Providence Saint Joseph Medical Center - Burbank	Burbank	California
United States	St. James Healthcare Cancer Care	Butte	Montana
United States	Rocky Mountain Oncology	Casper	Wyoming
United States	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas
United States	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan
United States	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas
United States	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas
United States	McLeod Regional Medical Center	Florence	South Carolina
United States	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina
United States	Big Sky Oncology	Great Falls	Montana
United States	Frontier Cancer Center	Great Falls	Montana
United States	Great Falls Clinic - Main Facility	Great Falls	Montana
United States	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana
United States	Northern Montana Hospital	Havre	Montana
United States	St. Peter's Hospital	Helena	Montana
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Independence Regional Health Center	Independence	Missouri
United States	Glacier Oncology, PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology at KRMC	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	CCOP - Kansas City	Kansas City	Missouri
United States	North Kansas City Hospital	Kansas City	Missouri
United States	Parvin Radiation Oncology	Kansas City	Missouri
United States	Research Medical Center	Kansas City	Missouri
United States	Saint Luke's Cancer Institute at Saint Luke's Hospital	Kansas City	Missouri
United States	St. Joseph Medical Center	Kansas City	Missouri
United States	Truman Medical Center - Hospital Hill	Kansas City	Missouri
United States	Columbia Basin Hematology	Kennewick	Washington
United States	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri
United States	Southwest Medical Center	Liberal	Kansas
United States	Liberty Hospital	Liberty	Missouri
United States	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois
United States	Community Medical Center	Missoula	Montana
United States	Guardian Oncology and Center for Wellness	Missoula	Montana
United States	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana
United States	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana
United States	Cancer Center of Kansas, PA - Newton	Newton	Kansas
United States	Menorah Medical Center	Overland Park	Kansas
United States	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas
United States	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas
United States	Rutherford Hospital	Rutherfordton	North Carolina
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Cancer Center of Kansas, PA - Salina	Salina	Kansas
United States	Huntsman Cancer Institute at University of Utah	Salt Lake City	Utah
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Group Health Central Hospital	Seattle	Washington
United States	Harborview Medical Center	Seattle	Washington
United States	Minor and James Medical, PLLC	Seattle	Washington
United States	Polyclinic First Hill	Seattle	Washington
United States	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington
United States	University Cancer Center at University of Washington Medical Center	Seattle	Washington
United States	Shawnee Mission Medical Center	Shawnee Mission	Kansas
United States	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	Cancer Care Northwest - Spokane South	Spokane	Washington
United States	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas
United States	Associates in Womens Health, PA - North Review	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas
United States	CCOP - Wichita	Wichita	Kansas
United States	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas
United States	Wesley Medical Center	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Southwest Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Continuous Complete Remission at 1 Year	A patient has a continuous complete remission at 1 year if they achieve a CR and are alive 365 days after registering to the study.	After induction, after consolidation, every 3 months during maintenance, and every three months after off treatment for up to a year	No
Secondary	Toxicity	Number of patients with Grade 3-5 adverse events that are related to study drug by given type of adverse event	Patients were assessed for adverse events after the induction cycle	Yes