Combination Chemotherapy in Treating Children With Very High Risk Acute Lymphocytic Leukemia

Leukemia Clinical Trial

Official title:

ALinC 17: Continuous Intensification for Very High Risk Acute Lymphocytic Leukemia (A.L.L.): A Pediatric Oncology Group Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003783
• Other study ID #: 9806
• Secondary ID: POG-9806CDR00000
• Status: Completed
• Phase: Phase 2
• First received: November 1, 1999
• Last updated: July 24, 2014
• Start date: March 1999
• Est. completion date: March 2007

Study information

• Verified date: July 2014
• Source: Children's 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 use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug and combining drugs in different ways may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of chemotherapy in treating children who have very high risk acute lymphocytic leukemia.

Description:

OBJECTIVES: I. Determine the feasibility of administering a new combination of agents during postinduction consolidation therapy in children with very high risk acute lymphocytic leukemia (VHR-ALL). II. Assess the tolerance of patients in remission of VHR-ALL for postconsolidation therapy with continuous intensification.

OUTLINE: Patients receive induction therapy on weeks 1-4. This consists of oral prednisone three times a day on days 1-28; vincristine IV on days 1, 8, 15, and 22; daunorubicin IV on days 8, 15, and 22; and asparaginase IM on days 2, 5, 8, 12, 15, and 19. Patients also receive methotrexate intrathecally (IT) on days 1 and 8. Patients with CNS 2 and 3 disease also receive methotrexate IT on days 15 and 22. Patients who achieve M2 bone marrow on day 29 receive oral prednisone three times a day on days 29-42; vincristine IV and daunorubicin IV over 15 minutes on days 29 and 36; and asparaginase IM on days 29, 32, 36, and 39. If bone marrow is M3 on day 29 or M2 or M3 on day 43, then patient is off study. Patients proceed to consolidation therapy on weeks 5-25. This consists of high dose methotrexate IV over 24 hours on weeks 6, 8, 16, and 18, followed by leucovorin calcium IV or orally every 6 hours for 5 doses; oral mercaptopurine on weeks 6-9 and 16-19; cytarabine IV over 6 hours followed by idarubicin IV over 15 minutes for 4 days; and filgrastim (G-CSF) subcutaneously (SQ) beginning on day 5 and continuing for about 10-14 days on weeks 10 and 20. Patients receive etoposide IV over 1 hour followed by cyclophosphamide IV over 10 minutes for 5 days and G-CSF SQ beginning on day 6 for 10-14 days on weeks 13 and 23. Methotrexate IT is administered on weeks 6, 8, 13, 16, 18, and 23. Patients then proceed to continuous intensification therapy during weeks 26-61. Patients receive vincristine IV, daunorubicin IV, and methotrexate IT on day 1, and oral dexamethasone twice a day on days 1-7 on weeks 26, 32, 38, 44, 50, and 56. Patients also receive high dose cytarabine IV over 1 hour, every 12 hours, for 4 doses, followed by asparaginase IM 3 hours after the last dose of cytarabine, on weeks 27, 33, 39, 45, 51, and 57. Oral mercaptopurine and methotrexate IM are administered on day 1 during weeks 29, 31, 35, 37, 41, 43, 47, 49, 53, 55, 59, and 61. Patients receive etoposide IV over 1-2 hours followed by cyclophosphamide IV during weeks 30, 36, 42, 48, 54, and 60. Patients then proceed to continuation therapy during weeks 62-126. Vincristine IV and cyclophosphamide IV are administered on weeks 62-65, 70-73, 78-81, 86-89, 94-97, 102-105, 110-113, and 118-121. Patients also receive oral dexamethasone twice a day for 7 days on weeks 62, 70, 78, 86, 94, 102, 110, and 118, and cytarabine IV on weeks 63, 65, 71, 73, 79, 81, 87, 89, 95, 97, 103, 105, 111, 113, 119, and 121. Oral mercaptopurine is administered daily during weeks 66-69, 74-77, 82-85, 90-93, 98-101, 106-109, 114-117, and 122-125 and methotrexate IM on weeks 66-69, 74-77, 82-85, 90-93, 98-101, 106-109, 114-117, and 122-125. Methotrexate IT is administered during weeks 62, 70, 78, 86, 94, 102, 110, and 118. Patients who are CNS 3 at diagnosis receive whole brain irradiation beginning at week 62 along with the first course of continuation therapy. These patients do not receive any methotrexate IT after week 62. Patients are followed monthly for 1 year, every 2 months for 1 year, every 3 months for 1 year, every 6 months for 1 year, then annually thereafter.

PROJECTED ACCRUAL: A total of 38 patients will be accrued for this study within 12 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: March 2007
• Est. primary completion date: November 2002
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 17 Years

Eligibility

DISEASE CHARACTERISTICS: Newly diagnosed B-cell precursor acute lymphocytic leukemia No L3 morphology Very poor prognosis CNS 3 (blasts and WBC greater than 5 microliters) OR Must meet all of the following criteria: No simultaneous trisomy 4 and 10 DNA index no greater than 1.16 (if FISH 4 and 10 unsatisfactory) No TEL-AML1 [t(12;21)] Meets at least 1 of the following: Has MLL (11q23) and/or BCR-ABL [t(9;22)] WBC greater than 100,000/mm3 Age over 12 (boys) or 16 (girls) OR Boys Girls WBC 8 12 greater than 80,000/mm3 9 13 greater than 60,000/mm3 10 14 greater than 40,000/mm3 11 15 greater than 20,000/mm3 Concurrent registration on stratum 6 of POG-9400 before 11/15/1999 OR Concurrent registration on stratum 4 of POG-9900 after 11/15/1999 Concurrent registration on POG-9201, POG-9705, or POG-9806 unless ineligible

PATIENT CHARACTERISTICS: Age: Children Performance status: Not specified Life expectancy:

Not specified Hematopoietic: See Disease Characteristics Hepatic: Not specified Renal: Not specified

PRIOR CONCURRENT THERAPY: See Disease Characteristics

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, 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

Drug:
• asparaginase

• cyclophosphamide

• cytarabine

• daunorubicin hydrochloride

• dexamethasone

• etoposide

• idarubicin

• leucovorin calcium

• mercaptopurine

• methotrexate

• prednisone

• vincristine sulfate

Radiation:
• radiation therapy

Locations

Country	Name	City	State
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	Montreal Children's Hospital	Montreal	Quebec
Canada	Children's Hospital of Eastern Ontario	Ottawa	Ontario
Canada	Centre Hospitalier de L'Universite Laval	Sainte Foy	Quebec
Netherlands	Academisch Ziekenhuis Groningen	Groningen
Puerto Rico	San Jorge Childrens Hospital	Santurce
Switzerland	Clinique de Pediatrie	Geneva
United States	University of New Mexico School of Medicine	Albuquerque	New Mexico
United States	Emory University Hospital - Atlanta	Atlanta	Georgia
United States	Eastern Maine Medical Center	Bangor	Maine
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Vermont Cancer Center	Burlington	Vermont
United States	West Virginia University Medical School, Charleston Division	Charleston	West Virginia
United States	Children's Memorial Hospital, Chicago	Chicago	Illinois
United States	Rush-Presbyterian-St. Luke's Medical Center	Chicago	Illinois
United States	University of Missouri-Columbia Hospital and Clinics	Columbia	Missouri
United States	Medical City Dallas Hospital	Dallas	Texas
United States	Simmons Cancer Center - Dallas	Dallas	Texas
United States	St. John's Hospital and Medical Center	Detroit	Michigan
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	Hurley Medical Center	Flint	Michigan
United States	Cook Children's Medical Center - Fort Worth	Fort Worth	Texas
United States	University of Texas Medical Branch	Galveston	Texas
United States	St. Vincent Hospital	Green Bay	Wisconsin
United States	Tripler Army Medical Center	Honolulu	Hawaii
United States	Baylor College of Medicine	Houston	Texas
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Nemours Children's Clinic	Jacksonville	Florida
United States	James H. Quillen College of Medicine	Johnson City	Tennessee
United States	Keesler Medical Center - Keesler AFB	Keesler AFB	Mississippi
United States	San Antonio Military Pediatric Cancer and Blood Disorders Center	Lackland Air Force Base	Texas
United States	Norris Cotton Cancer Center	Lebanon	New Hampshire
United States	Baptist Hospital of Miami	Miami	Florida
United States	Sylvester Cancer Center, University of Miami	Miami	Florida
United States	Mount Sinai Comprehensive Cancer Center	Miami Beach	Florida
United States	Midwest Children's Cancer Center	Milwaukee	Wisconsin
United States	West Virginia University Hospitals	Morgantown	West Virginia
United States	Tulane University School of Medicine	New Orleans	Louisiana
United States	Hope Children's Hospital	Oak Lawn	Illinois
United States	Oklahoma Memorial Hospital	Oklahoma City	Oklahoma
United States	Walt Disney Memorial Cancer Institute	Orlando	Florida
United States	Lucile Packard Children's Hospital at Stanford	Palo Alto	California
United States	Saint Jude Midwest Affiliate	Peoria	Illinois
United States	Maine Children's Cancer Program	Portland	Maine
United States	Carilion Roanoke Community Hospital	Roanoke	Virginia
United States	Sutter Cancer Center	Sacramento	California
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Kaiser Permanente-Southern California Permanente Medical Group	San Diego	California
United States	Naval Medical Center - San Diego	San Diego	California
United States	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California
United States	State University of New York Health Sciences Center - Stony Brook	Stony Brook	New York
United States	Madigan Army Medical Center	Tacoma	Washington
United States	Scott and White Clinic	Temple	Texas
United States	Arizona Cancer Center	Tucson	Arizona
United States	Natalie Warren Bryant Cancer Center	Tulsa	Oklahoma
United States	St. Mary's Hospital	West Palm Beach	Florida
United States	Via Christi Regional Medical Center	Wichita	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada,  Netherlands,  Puerto Rico,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assess the feasibility of delivering a new combination of agents during a 20 week post-induction consolidation phase		20 weeks	Yes