Title (COG AALL0434) Intensified Methotrexate, Nelarabine (Compound 506U78; IND #52611) and Augmented BFM Therapy for Children and Young Adults with Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia (ALL)
Principal Investigator Martin Brecher, MD
Study Number 108507
Summary AALL0434 is a COG group-wide Phase III study designed for patients with T-lineage acute lymphoblastic leukemia (T-ALL) or T-lineage lymphoblastic lymphoma (T-NHL) from 1-30 years of age. The study utilizes a 2 x 2 factorial design with augmented intensity BFM backbone. After a Day 29 risk assignment has been determined, patients will become eligible for treatment assignment or randomization. There is evidence that both Nelarabine (Compound 506U78) and high dose Methotrexate (HDMTX) are effective in preventing relapse in T-ALL. To specifically address the early treatment failures associated with T-All, this study will test the safety and efficacy of these two therapeutic interventions. T-NHL patients will be enrolled in a separate stratum and will receive the same common Induction therapy given to the t-ALL patients. T-NHL patients will be classified as Standard or High Risk, based upon flow cytometry studies performed on diagnostic bone marrow samples, and approach piloted in the recently completed lymphoblastic lymphoma study.
- T-ALL patients must be enrolled on AALL03B1 prior to treatment and enrollment on AALL0434.
- Patients must be greater than 1.00 and less than 31 years of age.
- Patients must have newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL) or T-lineage lymphoblastic lymphoma (T-NHL) Stage II-IV (see Appendix VIII). B-lineage lymphoblastic lymphoma will not be eligible of this study.
- Patients shall have had no prior cytotoxic chemotherapy with the exception of steroids and/or IT cytarabine. IT chemotherapy with cytarabine is allowed prior to registration for patient convenience. Patients diagnosed as having T-NHL or T-ALL with reparatory distress or hyperleukocytosis may require steroids prior to the initiation of additional systemic therapy. They are eligible for AALL0434 and will be stratified according to Section 3.3.5.
- Patients with prior seizure disorder requiring anti-convulsant therapy are not eligible to receive Nelarabine. In addition, patients with pre-existing Grade 2 (or greater) peripheral neurotoxicity, as determined prior to Induction treatment by the treating physician or a neurologist, are not eligible to receive Nelarabine.
- Pregnant or lactating females are ineligible. The medications used in this protocol may put the fetus at risk, and may cross into the breast mild and put the infant at risk.
- Patients with Down syndrome are ineligible to enroll onto this study.
- For T-NHL patient the following additional exclusion criteria apply:
- B-Precursor lymphoblastic lymphoma; Morphologically unclassifiable lymphoma; Absence of both b-call and T-cell phenotype markers in a case submitted as lymphoblastic lymphoma; CNS3-positive (see Section 3.3.2 for details) or testicular involvement