AALL1131

Principal Investigator: Phillip Barnette
Keywords: Pediatric , Oncology , Leukemia , B-cell ALL Department: Pediatric Administration
IRB Number: 00052541 Co Investigator:  
Specialty: Oncology
Sub Specialties:
Recruitment Status: Recruiting

Contact Information

Jennifer Craig
jennifer.craig@imail.org
8016624715

Brief Summary

Primary Objectives

1.To determine if the administration of post-Induction age adjusted ITT on an MBFM-IMHDM backbone will improve 5-year DFS of children with HR B-ALL compared to age adjusted IT MTX.

2. To determine, in a randomized fashion, if the cyclophosphamide + etoposide containing regimen (Experimental Arm 1) or the clofarabine + cyclophosphamide + etoposide combination regimen (Experimental Arm 2) will improve the 4-year DFS of children, adolescents, and young adults with VHR B-ALL compared to a modified MBFM-IMHDM regimen that contains a second IM (Control Arm).

Secondary Objectives

1.To determine the toxicity and tolerability of post-Induction age adjusted ITT compared to age adjusted IT MTX in children with HR B-ALL.

2.To determine the toxicity and tolerability of Experimental Arms 1 and 2 compared to the Control Arm in children, adolescents, and young adults with VHR B-ALL.

3. To determine whether a single-arm, modified Induction with limited anthracycline exposure and post-Induction therapy regimen with MBFM-IMIDM and reduced vincristine/steroid pulse frequency and enhanced supportive care in children with DS and HR B-ALL will result in a ≥ 65% 5-year DFS and < 10% Induction mortality.

4. To describe the outcomes for children and young adults with Ph-like B-ALL and a predicted TKI-sensitive mutation treated with dasatinib plus MBFM-IMHDM. 

5. To determine the toxicity and tolerability of MBFM-IMIDM in children with DS and HR B-ALL.

6. To estimate overall survival (OS) rates both overall and by regimen a) for HR B-ALL and b) VHR B-ALL patients.

7. To determine the incidence of ON, defined by MR imaging, and to characterize the natural history of clinically silent ON in children, adolescents and young adults 10 years of age and greater and to assess the role of drugs (i.e., asparaginase and methotrexate) in addition to corticosteroids, in the risk for development of ON.

8. To determine if the prevalence of cognitive deficits measured by CogState, in children (ages 6 to 11 years) with HR- and VHR B-ALL at 1 year off therapy, is significantly higher than the normative population (> 14%) in the following domains: working memory, executive function, visual motor, processing speed, and visual attention.

9. To compare the drug delivery of vincristine, pegaspargase and methotrexate during Induction, Consolidation, Delayed Intensification and Interim Maintenance II in 16-30 year olds treated on the control arm of the VHR study to that of adolescents and young adults (AYAs) with ALL treated with the same therapy on the C10403 adult cooperative group trial.

Added with Amendment 3B:

1.3 Exploratory Obejctive

1.3.1 To determine if the reduction of MRD from end-Induction to end-Consolidation is greater for children, adolescents, and young adults with VHR B-ALL receiving Experimental Arm 1 compared to the Control Arm.

 

Inclusion Criteria

1) Patients must be enrolled on AALL08B1 prior to enrollment on AALL1131.
 
2) Patients must be > 365 days and < 31 years of age

2.5) Patients must meet adequate organ function requirements. 
 
3) White Blood Cell Count (WBC) Criteria Age 1-9.99 years: WBC ≥ 50 000/μL Age 10-30.99 years: Any WBC Age 1-30.99 years: Any WBC with:
 
a) Testicular leukemia
 
b) CNS leukemia (CNS3)
 
c) Steroid pretreatment (see Section 3.3 of the protocol)
 
4) Patients must have newly diagnosed  B lymphoblastic leukemia (2008 WHO classification) (also termed B-precursor acute lymphoblastic leukemia. Patients with Down syndrome are also eligible.

 

REGULATORY REQUIREMENTS

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

All institutional, FDA, and NCI requirements for human studies must be met.

Exclusion Criteria

With the approval of Amendment 3B, patients may enroll concurrently on COG AALL1421.

1) With the exception of steroid pretreatment (defined in Section 3.3) or the administration of intrathecal cytarabine, patients must not have received any prior cytotoxic chemotherapy for either the current diagnosis of B-ALL or any cancer diagnosed  prior to the initiation of protocol therapy on AALL1131. Patients cannot have secondary B-ALL that developed after treatment of a prior malignancy with cytotoxic chemotherapy. Patients receiving prior steroid therapy may be eligible for AALL1131 as defined below (Section 3.3).
 
2) Patients with BCR-ABL1 fusion (not eligible for post-Induction therapy on this study; non-DS patients may be eligible to enroll in AALL1122 or successor COG Ph+ ALL trial by Day 15 Induction)
 
3) DS HR B-ALL patients with Induction failure or BCR-ABL1
 
4) VHR B-ALL patients with significant dysfunction at the time of post-Induction randomization defined as: Direct bilirubin > 1.5 x upper limit of normal (ULN) for age, SGPT (ALT) > 3 x upper limit of normal (ULN) for age, Lipase > 2.0 x upper limit of normal (ULN) for age, renal function defined as creatinine clearance or radioisotope GFR < 70 mL/min/1.73m2 or a serum creatinine based on age/gender as defined in the protocol table 3.2.6.3
 
5) VHR B-ALL patients with known Hepatitis B or C infection or history of cirrhosis at the time of post-Induction randomization
 
6) Female patients who are pregnant are ineligible since fetal toxicities and teratogenic effects have been noted for several of the study drugs. 
 
7) Lactating females are not eligible unless they have agreed not to breast-feed their infant.

8) Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained.

9) Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation.

10) Eligibility criteria for the Incidence and Natural History of Osteonecrosis study

• Patients must be 10 years of age or greater at the time of B-ALL diagnosis, enrolled on AALL1131.

• Patients with Down syndrome are not eligible

11) Eligibility criteria for the Longitudinal, Computerized Assessment of Neurocognitive Functioning study

• Patients must be aged 6 to 11 years at time of B-ALL diagnosis, enrolled on AALL1131

• Patients must be English-, French- or Spanish-speaking (languages in which the assessment is available)

• Patients must have no known history of neurodevelopmental disorder prior to diagnosis of B-ALL (e.g., Down syndrome, Fragile X, William’s Syndrome, mental retardation)

• Patients must have no significant visual impairment that would prevent computer use and recognition of the visual test stimuli

12)  Eligibility criteria for the NCI standard risk patients from AALL0932 enrolling on this study at the end of Induction:

 

13) Patients enrolled on AALL0932, without Down syndrome, meeting the following criteria will NOT be eligible to continue on AALL0932 but WILL BE eligible to enroll on the HR B-ALL stratum of this study at the end of Induction: a) Without favorable cytogenetics (no ETV6-RUNX1 or double trisomies 4+10), with Day 8 PB MRD ≥ 1% and Day 29 BM MRD < 0.01%. b) With favorable cytogenetics (ETV6-RUNX1 or double trisomies 4+10), with any Day 8 PB MRD and Day 29 BM MRD > 0.01%. Both NCI SR and HR patients without Down syndrome and with testicular disease at diagnosis, who do not meet other VHR criteria, will be eligible for the HR stratum.

 

14) Patients enrolled on AALL0932, without Down syndrome, meeting the following criteria will NOT be eligible to continue on AALL0932 but WILL BE eligible to enroll on the VHR B-ALL stratum of this study at the end of Induction: a) iAMP21 b) MLL rearrangement c) Hypodiploidy (n< 44 chromosomes and/or a DNA index < 0.81) d) Induction Failure (M3 BM at Day 29)

 

e) Without favorable cytogenetics (no ETV6-RUNX1 or double trisomies 4+10), with Day 29 BM MRD > 0.01%

15) Patients enrolled on AALL0932, with Down syndrome, meeting the following criteria will NOT be eligible to continue on AALL0932 but WILL BE eligible to enroll on the DS HR B-ALL stratum of this study at the end of Induction: a) Day 29 MRD ≥ 0.01% b) MLL rearrangement c) Hypodiploidy (n< 45 chromosomes and/or DNA index < 0.81)

 

16) DS HR B-ALL patients initially enrolled on AALL0932 or this study who have Induction Failure (M3 BM Day 29) or Philadelphia chromosome (BCR-ABL1) will not be eligible for post-Induction therapy on either trial (AALL0932 or AALL1131).

 

Ph-like patients are not eligible for the osteonecrosis study.