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
This study will include T-ALL and T-NHL patients.
All T-ALL and T-NHL patients will receive the same Induction sequence. Subsequent therapy will be based on risk assignment. The treatment assignment is determinded on Day 29. After a Day 29 risk assignment has been determined via participation on AALL08B1, patients will become eligible for treatment assignment or randomization.
Thee are 4 treatment regimens for patients with T-ALL:
Arm A: Augmented BFM with Cpaizzi MTX, no Nelarabine (CMTX)
Arm B: Augmented BFM iwht Capissi MTX plus Nelarabine (CMTX + Nel)
Arm C: Augmented BFM with High Dose MTX, no Nelarabine (HDMTX)
Arm D: Augmented BFM with High Dose MTX plus Nelarabine (HDMTX + Nel)
There are 2 treatment regimens for patients with T-NHL:
Arm A: Augmented BFM with Capizzi MTX, no Nelarabine (CMTX)
Arm B: Augmented BFM with Capizzi MTX, plus Nelarabine (CMTX + Nel)
The safety phase, which is now completed, randomized the high risk patients to receive or not receive Nelarabine. Now, during the efficacy phase of the study, intermediate risk patients will also be randomized to receive or not to receive Nelarabine at a dose of 650 mg/m2/day for 5 days during the Consolidation, Delayed Intensification and Maintenance phases of therapy. All patients will receive only one Delayed Intensification course and all Intermediate and High Risk patients will receive prophylactic cranial radiation (1200 cGy) either during Consolidation (if randomized to treatment Arm A (CMTX) or Arm B (CMTX + Nel)) or Delayed Intensification (if randomized to treatment Arm C (HDMTX) or Arm D (HDMTX + Nel)). All Intermediate and High Risk patients classified as CNS3 will be non-randomly assigned to receive HD MTX on either Arm C (HDMTX) or Arm D (HDMTX + Nel) and receive cranial radiation therapy (CRT) (1800 cGy) during Delayed Intensification. Patients with testicular leukemia will be non-randomly assigned to receive HDMTX on either Arm C (HDMTX) or Arm D (HDMTX + Nel) and will receive testicular radiation therapy (TRT) (2400 cGy) during Consolidation therapy, if testicular disease does not resolve by the end of Induction therapy. Low-risk patients, who are NCI standard risk by age and WBC, with no testicular disease at diagnosis, CNS1 and rapid early responders (RERs) with an M1 marrow by Day 15, and minimal residual disease (MRD) and amp;lt; 0.1% on Day 29, have an excellent outcome and therefore will not receive Nelarabine in either the safety or efficacy phases; nor will they receive cranial radiation.
For the T-NHL patients, a bone marrow MRD evaluation will be completed at diagnosis.
Standard Risk T-NHL patients with and amp;lt;1% disease in bone marrow at diagnosis are not eligible for the Nelarabine randomization and will be non-randomly assigned only to Arm A (CMTX).
High Risk T-NHL patients with and amp;gt;1% disease in bone marrow at diagnosis are elibible for Nelarabine randomization and will enter Arm A or Arm B. There will be no CRT during consolidation. T-NHL patients who are CNS-positivie or who have testicular disease will be excluded.
Induction Failure T-NHL patients - who fail to achieve at least a PR at the end of Induction will be non-randomly assigned to Arm B. Patients who do not attain at least a PR by end of Consolidation therapy will be removed from protocol therapy.
1) Patients with T-ALL must be enrolled on AALL08B1 prior to treatment and enrollment on AALL0434. 2) Patients must be greater than 1.00 and less than 31 years of age. 3) Patients must have newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL) or T-lineage lymphoblastic lymphoma (T-NHL) Stage II-IV. . A diagnosis of T-ALL is established when leukemic blasts lack myeloperoxidase or evidence of B-lineage derivation (CD19/CD22/CD20), and express either surface or cytoplasmic CD3 or two or more of the antigens CD8, CD7, CD5, CD4, CD2 or CD1a. If surface CD3 is expressed on all leukemic cells, additional markers of immaturity, including TdT, CD34 or CD99 will be assessed for expression. Cases with uncertain expression will receive additional review within the appropriate COG reference laboratory. 4) 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. This is usually done at the time of the diagnostic bone marrow or venous line placement to avoid a second lumbar puncture. (Note: the CNS status must be determined based on a sample obtained prior to the administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment as described in Section 3.3). Systemic chemotherapy must begin within 72 hours of this IT therapy. Patients receiving prior steroid therapy are eligible for study. Steroid pretreatment may alter the risk group assessment. The dose and duration of previous steroid therapy should be carefully documented. Patients diagnosed as having T-NHL or T-ALL with respiratory distress or hyperleukocytosis may require steroids prior to the initiation of additional systemic therapy. These patients are eligible. 5) All patients and/or their parents or legal guardians must sign a written informed consent. 6) All institutional, FDA, and NCI requirements for human studies must be met. 7) Spanish speaking subjects are eligible.
Patients with T-NHL are ineligible for AALL03B1/AALL08B1 and can enroll directly on the AALL0434 study.