AALL1231

Principal Investigator: Phillip Barnette
Keywords: COG , T cell ALL , T cell Lymphoblastic Lymphoma Department: Pediatric Administration
IRB Number: 00077499 Co Investigator:  
Specialty: Oncology
Sub Specialties:
Recruitment Status: Recruiting

Contact Information

Jennifer Craig
jennifer.craig@imail.org
8016624715

Brief Summary

Primary Aims

To compare (event free survival) EFS in patients with newly diagnosed T-ALL and T-LLy who are randomized to a modified ABFM backbone versus bortezomib plus the modified ABFM backbone.

Secondary Aims

To determine the safety and feasibility of modifying standard therapy for T-ALL and T-LLy based on the results of UKALL 2003, which includes a dexamethasone-based Induction, additional doses of pegaspargase (PEG-ASP) during Induction and Delayed Intensification (DI), and dexamethasone pulses during Maintenance therapy

To determine if prophylactic (presymptomatic) cranial radiation therapy (CRT) can be safely and effectively eliminated in the 85-90% of T-ALL patients classified as standard or intermediate risk.

To determine the proportion of EOC MRD ≥ 0.1% T-ALL patients who become MRD negative
(undetectable by flow cytometry) after intensification of chemotherapy, using three high risk (HR)
BFM blocks, and to compare EFS between the patients who become MRD negative after the three HR BFM
blocks and continue on chemotherapy with those who continue to have detectable MRD and are eligible
for other treatment strategies, including hematopoietic stem cell transplant (HSCT). Similarly, to
compare the EFS between very high risk (Induction failure) T-LLy patients treated with HR BFM
intensification blocks who have partial or complete response (PR or CR) with those who do not
respond (NR).

Correlative Aims
To investigate the prognostic significance of Day 29 BM MRD in T-LLy patients.

To determine if protein expression patterns can predict bortezomib response and drug
resistance in T-ALL

To analyze and target relevant signaling pathways in T-ALL blasts, focusing on Early T
cell Precursor (ETP) ALL

Inclusion Criteria

INCLUSION CRITERIA

a. Classification Study:

• T-ALL: T-ALL patients must be enrolled on AALL08B1 or Project: Every Child (APEC14B1, if open for the classification of ALL patients) prior to treatment and enrollment on AALL1231.

b. Age at Diagnosis: All patients must be > 1 and < 31 years of age.

c. Diagnosis: Patients must have newly diagnosed T-Lymphoblastic Leukemia (T-ALL) or

T-Lymphoblastic Lymphoma (T-LLy) Stages II-IV). .

d. Informed consent: All patients and/or their parents or legal guardians must sign a written

informed consent. Assent, when appropriate, will be obtained according to institutional guidelines

Exclusion Criteria

With the approval of Amendment 3, "pretreatment with hydroxyurea" is a caveat to the exclusion criteria of prior therapy. Additionally, steroid pretreatment has an added exception. Patients may have a single dose of dexamethasone used during sedation to prevent or treat airway edema prior to initiating treatment on this study.  

Prior Therapy: Patients must not have received any cytotoxic chemotherapy for either the current diagnosis of T-ALL, T-L-Ly or for any cancer diagnosis prior to the initiation of protocol therapy on AALL1231, with the exception of:

• Steroid pretreatment [60mg/m2/day prednisone (or 48 mg/m2/day of methylprednisolone) for ≤ 120 (5 days) hours in the 7 days prior to initiating Induction chemotherapy or for 336 hours (14 days) in the 28 days prior to initiating Induction chemotherapy]. Prior exposure to ANY steroids that occurred > 28 days before the initiation of protocol therapy does not affect eligibility. 

• Intrathecal cytarabine; or

• 600 cGy of chest irradiation, if medically necessary.

Pre-treatment with dexamethasone in the 28 days prior to initiation of protocol therapy is not allowed. Inhalation steroids and topical steroids are not considered pretreatment.

b. Peripheral neurotoxicity: Pre-existing ≥ grade 2 sensory or motor peripheral neurotoxicity.

c. Seizures disorder: Uncontrolled seizure disorder

d. Diagnosis of Down syndrome (Trisomy 21)

e. Patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential.

f. Lactating females who plan to breastfeed.

g. Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation.

h Patient has hypersensitivity to bortezomib, boron, or mannitol.

i Serious medical or psychiatric illness likely to interfere with participation in this clinical study.

j Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and within 30 days of any dose of bortezomib.