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Pegaspargase and Combination Chemotherapy in Treating Younger Patients With Newly Diagnosed High-Risk Acute Lymphoblastic Leukemia (Closed to Accrual 4-22-2011)

Information source: Children's Oncology Group
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

Intervention: pegaspargase (Drug); cytarabine (Drug); vincristine sulfate (Drug); doxorubicin hydrochloride (Drug); cyclophosphamide (Drug); prednisone (Drug); dexamethasone (Drug); methotrexate (Drug); daunorubicin hydrochloride (Drug); mercaptopurine (Drug); thioguanine (Drug); prophylactic cranial irradiation (Radiation); laboratory biomarker analysis (Other)

Phase: N/A

Status: Active, not recruiting

Sponsored by: Children's Oncology Group

Official(s) and/or principal investigator(s):
ZoAnn Dreyer, MD, Principal Investigator, Affiliation: Children's Oncology Group

Summary

This pilot clinical trial studies the side effects of pegaspargase when given together with combination chemotherapy in treating patients with newly diagnosed high-risk acute lymphoblastic leukemia. Pegaspargase may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) together with pegaspargase may kill more cancer cells.

Clinical Details

Official title: Intensified PEG-Asparaginase in High Risk Acute Lymphoblastic Leukemia (ALL): A Pilot Study

Study design: Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Percentage of patients which tolerate at least 8 of the 12-14 total doses of pegaspargase assessed by Common Terminology Criteria for Adverse Events (CTCAE) version(v)4.0

Secondary outcome: Incidence of toxicity incidents assessed by CTCAE version 4.0

Detailed description: PRIMARY OBJECTIVES: I. To demonstrate that biweekly intravenous (IV) pegaspargase beginning with Consolidation and ending with completion of delayed intensification (DI) in combination with hemi-augmented BFM therapy (hABFM) is feasible and safe in children with high risk (HR) acute lymphoblastic leukemia (ALL). OUTLINE: Patients are stratified according to risk assignment (high-risk [HR]-average [day 29 minimal residual disease (MRD) < 0. 01%] vs HR-high [MRD >= 0. 01%, presence of central nervous system [CNS]3 leukemia, testicular disease, myeloid/mixed lineage leukemia [MLL] rearrangement, hypodiploidy, or steroid therapy within the past month]). Patients are assigned to 1 of 2 treatment groups.* (Note: *Amendment 2 [4-22-2011] requires changes in the regimens. See the changes below, after Maintenance therapy.) INDUCTION THERAPY: All patients receive cytarabine intrathecally (IT) on day 1; vincristine sulfate IV on days 1, 8, 15, and 22; prednisone IV or orally (PO) twice daily (BID) on days 1-28; daunorubicin hydrochloride IV over 15 minutes on days 1, 8, 15, and 22; methotrexate IT on days 8 and 29*; and pegaspargase IV over 1-2 hours on day 4. (Note: *Patients with CNS3 disease [white blood cells [(WBC)] >= 5/uL and positive for blasts on cytospin] also receive methotrexate IT on days 15 and 22.) CONSOLIDATION THERAPY (begins on day 36 of induction therapy): GROUP A (HR-AVERAGE): Patients receive cyclophosphamide IV over 1 hour on days 1 and 29; cytarabine IV over 15 minutes or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO once daily (QD) on days 1-14 and 29-42; vincristine sulfate IV on days 15, 22, 43, and 50; methotrexate IT on days 1, 8, 15*, and 22*; and pegaspargase IV over 1-2 hours on days 15 and 43. GROUP B (HR-HIGH): Patients receive cyclophosphamide, cytarabine, mercaptopurine, vincristine sulfate, and methotrexate as in Group A. Beginning on day 1, patients also receive pegaspargase IV over 1-2 hours every 2 weeks. Patients with CNS3 disease undergo cranial radiotherapy QD for 10 days and patients with testicular disease undergo testicular radiotherapy QD for 12 days, beginning on day 1 of consolidation. (Note: *Patients with CNS3 disease [WBC >= 5/uL and positive for blasts on cytospin] do not receive methotrexate IT on days 15 and 22.) Interim maintenance (IM) therapy (begins on day 57 of consolidation): GROUP A: Patients receive vincristine sulfate IV on days 1, 11, 21, 31, and 41; methotrexate IV over 10-15 minutes on days 1, 11, 21, 31, and 41; methotrexate IT on days 1 and 31; and pegaspargase IV over 1-2 hours on days 2 and 22. GROUP B: Patients receive vincristine sulfate and methotrexate as in Group A. Beginning on day 1, patients also receive pegaspargase IV over 1-2 hours every 2 weeks. DI therapy (begins on day 57 of IM): GROUP A: Patients receive vincristine sulfate IV on days 1, 8, 15, 43, and 50; dexamethasone IV or PO BID on days 1-7 and 15-21; doxorubicin hydrochloride IV over 15 minutes on days 1, 8, and 15; cyclophosphamide IV over 1 hour on day 29; cytarabine IV over 15 minutes or SC on days 29-32 and 36-39; thioguanine PO on days 29-42; methotrexate IT on days 1, 29, and 36; and pegaspargase IV over 1-2 hours on days 4 and 43. GROUP B: Patients receive vincristine sulfate, dexamethasone, doxorubicin hydrochloride, cyclophosphamide, cytarabine, thioguanine, and methotrexate as in Group A. Beginning on day 1, patients also receive pegaspargase IV over 1-2 hours every 2 weeks. MAINTENANCE THERAPY (MT; begins on day 57 of DI): All patients receive vincristine sulfate IV on days 1, 29, and 57; prednisone PO BID on days 1-5, 29-33, and 57-61; mercaptopurine PO on days 1-84; methotrexate IT on day 1; and methotrexate PO BID on days 8, 15, 22, 29*, 36, 43, 50, 57, 64, 71, and 78. In both groups, MT repeats every 12 weeks until total duration of therapy is 2 years from the start of IM for female patients and 3 years from the start of IM for male patients. Patients in Group B who did not undergo radiotherapy to the brain during consolidation therapy undergo prophylactic cranial radiotherapy (CR) daily for 8 days. ([Note: *Patients in Group A also receive methotrexate IT on day 29 of courses 1-4 [no oral methotrexate]). REVISED MT (RMT): The regimen is the same as standard MT, but 2 of the doses of IT methotrexate are omitted (day 29 of courses 3 and 4).

Eligibility

Minimum age: 1 Year. Maximum age: 30 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Patients must be eligible for and enrolled on AALL03B1 or the successor

classification study

- Patients must have newly diagnosed high-risk B-precursor acute lymphoblastic leukemia

(ALL)

- WBC criteria

- Age 1. 00-9. 99 years: WBC >= 50,000/uL

- Age 10. 00 - 30. 99 years: Any WBC

- Prior steroid therapy: Any WBC

- Patients with testicular leukemia: Any WBC

- Patients shall have had no prior cytotoxic chemotherapy with the exception of

steroids and intrathecal cytarabine

- Intrathecal chemotherapy with cytarabine is allowed prior to registration for patient

convenience; this is usually done at the time of the diagnostic bone marrow or venous line placement to avoid a second lumbar puncture; the CNS status must be determined based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment; systemic chemotherapy must begin within 72 hours of this intrathecal therapy

- Patients receiving prior steroid therapy are eligible for study; the dose and

duration of previous steroid therapy should be carefully documented

- All patients and/or their parents or legal guardians must sign a written informed

consent

- All institutional, Food and Drug Administration (FDA), and National Cancer Institute

(NCI) requirements for human studies must be met Exclusion Criteria:

- Pregnant female patients are ineligible; pregnancy tests with a negative result must

be obtained in all post-menarchal females; males and females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method; lactating females must agree that they will not breastfeed a child while on this study

- Patients with Down syndrome (DS) are ineligible since excessive toxicities and death

have been noted for those enrolled on AALL0232 receiving the prednisone/Capizzi methotrexate (PC) arm of treatment, which is the backbone regimen for the current study

Locations and Contacts

Phoenix Childrens Hospital, Phoenix, Arizona 85016, United States

Miller Children's Hospital, Long Beach, California 90806, United States

Children's Hospital Los Angeles, Los Angeles, California 90027, United States

Rady Children's Hospital - San Diego, San Diego, California 92123, United States

University of California San Francisco Medical Center-Parnassus, San Francisco, California 94143, United States

Nemours Children's Clinic-Jacksonville South, Jacksonville, Florida 32207, United States

Children's Healthcare of Atlanta - Egleston, Atlanta, Georgia 30322, United States

University of Kentucky, Lexington, Kentucky 40536, United States

Kosair Children's Hospital, Louisville, Kentucky 40202, United States

C S Mott Children's Hospital, Ann Arbor, Michigan 48109, United States

The Steven and Alexandra Cohen Children's Medical Center of New York, New Hyde Park, New York 11040, United States

University of North Carolina, Chapel Hill, North Carolina 27599, United States

Nationwide Children's Hospital, Columbus, Ohio 43205, United States

Children's Hospital of Eastern Ontario, Ottawa, Ontario K1H 8L1, Canada

Legacy Emanuel Children's Hospital, Portland, Oregon 97227, United States

Legacy Emanuel Hospital and Health Center, Portland, Oregon 97227, United States

Children's Oncology Group, Philadelphia, Pennsylvania 19104, United States

Baylor College of Medicine, Houston, Texas 77030, United States

Methodist Children's Hospital of South Texas, San Antonio, Texas 78229, United States

Princess Margaret Hospital for Children, Perth, Western Australia 6008, Australia

Additional Information

Starting date: February 2009
Last updated: April 10, 2015

Page last updated: August 23, 2015

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