Clinical trial NCT00866307: Pegaspargase and Combination Chemotherapy in Treating Younger Patients With Newly Diagnosed High-Risk Acute Lymphoblastic Leukemia (Closed to Accrual 4-22-2011)
Official title: Intensified PEG-Asparaginase in High Risk Acute Lymphoblastic Leukemia (ALL): A Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Lymphoblastic Leukemia
Adult B Acute Lymphoblastic Leukemia
Childhood B Acute Lymphoblastic Leukemia
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-03-20
Enrollment: 104
Sex: ALL
Minimum age (years): 1
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: AALL08P1 Safety Outcome
timeFrame: Consolidation through Delayed Intensification
measure: AALL08P1 Feasibility Outcome
timeFrame: Consolidation through Delayed Intensification
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Childrens Hospital
state: Arizona
city: Long Beach
country: United States
facility: Miller Children's and Women's Hospital Long Beach
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Madera
country: United States
facility: Valley Children's Hospital
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital - San Diego
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center-Mount Zion
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center-Parnassus
state: California
city: Torrance
country: United States
facility: Harbor-University of California at Los Angeles Medical Center
state: California
city: Jacksonville
country: United States
facility: Nemours Children's Clinic-Jacksonville
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta - Egleston
state: Georgia
city: Oak Lawn
country: United States
facility: Advocate Children's Hospital-Oak Lawn
state: Illinois
city: Indianapolis
country: United States
facility: Saint Vincent Hospital and Health Care Center
state: Indiana
city: Lexington
country: United States
facility: University of Kentucky/Markey Cancer Center
state: Kentucky
city: Louisville
country: United States
facility: Norton Children's Hospital
state: Kentucky
city: Ann Arbor
country: United States
facility: C S Mott Children's Hospital
state: Michigan
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: New Hyde Park
country: United States
facility: The Steven and Alexandra Cohen Children's Medical Center of New York
state: New York
city: Chapel Hill
country: United States
facility: UNC Lineberger Comprehensive Cancer Center
state: North Carolina
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Dayton
country: United States
facility: Dayton Children's Hospital
state: Ohio
city: Portland
country: United States
facility: Legacy Emanuel Children's Hospital
state: Oregon
city: Portland
country: United States
facility: Legacy Emanuel Hospital and Health Center
state: Oregon
city: Philadelphia
country: United States
facility: Children's Oncology Group
state: Pennsylvania
city: Houston
country: United States
facility: Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Methodist Children's Hospital of South Texas
state: Texas
city: Parkville
country: Australia
facility: Royal Children's Hospital
state: Victoria
city: Perth
country: Australia
facility: Princess Margaret Hospital for Children
state: Western Australia
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario
state: Ontario
Study officials:
affiliation: Children's Oncology Group
name: ZoAnn E Dreyer
role: PRINCIPAL_INVESTIGATOR
References: