Phase 3
N=1,895
Combination Chemotherapy in Treating Young Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or T-cell Lymphoblastic Lymphoma
T Acute Lymphoblastic Leukemia · T Lymphoblastic Lymphoma
Bottom Line
View on ClinicalTrials.gov: NCT00408005 ↗Enrolled (actual)
1,895
Serious AEs
5.6%
Results posted
Jun 2019
Primary outcome: Primary: Disease-free Survival (DFS) for Randomized Nelarabine T-ALL Cohort (Arm I vs. Arm II vs. Arm III vs. Arm IV) — 89.01; 90.53; 78.07; 86.46 percent probability
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Asparaginase (Drug); Cyclophosphamide (Drug); Cytarabine (Drug); Daunorubicin Hydrochloride (Drug); Dexamethasone (Drug); Doxorubicin Hydrochloride (Drug); Laboratory Biomarker Analysis (Other); Leucovorin Calcium (Drug); Mercaptopurine (Drug); Methotrexate (Drug); Nelarabine (Drug); Pegaspargase (Drug); Prednisone (Drug); Radiation Therapy (Radiation); Thioguanine (Drug); Vincristine Sulfate (Drug)
- Age
- Pediatric, Adult · 1+ yrs
- Sex
- All
- Sponsor
- National Cancer Institute (NCI)
- Primary completion
- Sep 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Disease-free Survival (DFS) for Randomized Nelarabine T-ALL Cohort (Arm I vs. Arm II vs. Arm III vs. Arm IV) |
89.01; 90.53; 78.07; 86.46 | — |
| PRIMARY Disease-free Survival (DFS) for Randomized Nelarabine T-ALL Cohort (Arm I + Arm III vs. Arm II + Arm IV) |
82.96; 88.30 | — |
| PRIMARY Disease-free Survival (DFS) for Randomized Methotrexate T-ALL Cohort (Arm I vs. Arm II vs. Arm III vs. Arm IV) |
91.76; 90.53; 86.06; 84.89 | — |
| PRIMARY Disease-free Survival (DFS) for Randomized Methotrexate T-ALL Cohort (Arm I + Arm II vs. Arm III + Arm IV) |
91.45; 85.78 | — |
| PRIMARY Disease-free Survival (DFS) for T-cell Lymphoblastic Lymphoma (T-LLy) Cohort |
87.4; 85.1; 85.0; 100 | — |
| SECONDARY Cumulative Incidence of CNS Relapse for T-ALL by Risk Group |
1.85; 1.92; 1.16; 1.08; 9.1; 0.85 | — |
Summary
This randomized phase III trial is studying different combination chemotherapy regimens and their side effects and comparing how well they work in treating young patients with newly diagnosed T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective in treating T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma. After a common induction therapy, patients were risk assigned and eligible for one or both post-induction randomizations: Escalating dose Methotrexate versus High Dose Methotrexate in Interim Maintenance therapy, No Nelarabine versus Nelarabine in Consolidation therapy. T-ALL patients are risk assigned as Low Risk, Intermediate Risk or High Risk. Low Risk patients are not eligible for the Nelarabine randomization, Patients with CNS disease at diagnosis were assgined to receive High Dose Methotrexate, patients who failed induction therapy were assigned to receive Nelarabine and High Dose Methotrexate. T-LLy patients were all assigned to escalating dose Methotrexate and were risk assigned as Standard Risk, High Risk and induction failures. Standard risk patients did not receive nelarabine, High risk T-LLy patients were randomized to No Nelarabine versus Nelarabine, and Induction failures were assigned to receive Nelarabine.
Eligibility Criteria
Inclusion Criteria
- T-ALL patients must be enrolled on AALL08B1 prior to treatment and enrollment on AALL0434
- Patients must have newly diagnosed T-ALL or T-lineage lymphoblastic lymphoma (T-NHL) stage II-IV; B-lineage lymphoblastic lymphoma will not be eligible for this study; a diagnosis of T-ALL is established when leukemic blasts lack myeloperoxidase or evidence of B-lineage derivation (cluster of differentiation [CD]19/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 transmission disequilibrium test (TdT), CD34 or CD99 will be assessed for expression; cases with uncertain expression will receive additional review within the appropriate Children's Oncology Group (COG) reference laboratory
- T-NHL PATIENTS:
- For T-NHL patients with tissue available for flow cytometry, the criterion for diagnosis should be analogous to T-ALL; for tissue processed by other means (i.e. paraffin blocks), the methodology and criteria for immunophenotypic analysis to establish the diagnosis of T-NHL defined by the submitting institution will be accepted
- Prior therapy restrictions
- 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 administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment); systemic chemotherapy must begin within 72 hours of this IT therapy
- 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; they are eligible for AALL0434 and will be stratified, based on the initial complete blood count (CBC); steroid pretreatment may alter the risk group assessment; if the T-ALL patient's clinical status precludes a lumbar puncture within 48 hours of the initiation of steroid therapy, T-ALL patients CANNOT be classified as low risk and will be Intermediate or high risk based on the results of the day 29 marrow as above; patients with T-NHL who receive steroid pre-treatment will be classified as high risk; the dose and duration of previous steroid therapy should be carefully documented
- For the management of airway compromise, patients who have received emergent chest irradiation up to 600 cGy will be eligible for this study
- Patients with a 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; these restrictions in eligibility are designed to prevent excessive nelarabine-induced central and peripheral neurotoxicity in at-risk patients; for the purposes of this study, this includes any patient that has received anticonvulsant therapy to prevent/treat seizures in the prior two years
Exclusion Criteria
- Pregnant or lactating females are ineligible
- Patients with Down syndrome are ineligible to enroll onto this study
- For T-NHL patients the following additional exclusion criteria apply:
- B-precursor lymphoblastic lymphoma
- Morphologically unclassifiable lymphoma
- Absence of both B-cell and T-cell phenotype markers in a case submitted as lymphoblastic lymphoma
- CNS3-positive or testicular involvement
Data sourced from ClinicalTrials.gov (NCT00408005). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.