T Acute Lymphoblastic Leukemia, T Lymphoblastic Lymphoma
Conditions
Brief 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.
Detailed description
PRIMARY OBJECTIVES: I. To determine, through randomization, the relative safety and efficacy of the addition of nelarabine (Compound 506U78) to augmented Berlin-Frankfurt-Münster (BFM) therapy (Regimen C, Children's Cancer Group \[CCG\]-1961). II. To determine the relative safety and efficacy of high dose methotrexate (5 g/m\^2) with leucovorin (leucovorin calcium) rescue compared to escalating methotrexate without leucovorin rescue plus pegaspargase (Capizzi I) delivered during interim maintenance. III. To gain preliminary data on the use of nelarabine in patients with high risk T-cell lymphoblastic lymphoma and its effect on long-term survival. SECONDARY OBJECTIVES: I. To determine the relative safety and efficacy of withholding radiation in patients with low risk T-cell acute lymphoblastic leukemia (T-ALL), while treating Intermediate and high risk patients with 1200 cGy of prophylactic cranial radiation. OUTLINE: This is a randomized, controlled, factorial-group, multicenter study. GROUP 0 (INDUCTION THERAPY): All patients (T-ALL and T-LLy) receive cytarabine intrathecally (IT) on day 1; vincristine sulfate intravenously (IV) on days 1, 8, 15, and 22; prednisone IV or orally (PO) twice daily (BID) on days 1-28; pegaspargase intramuscularly (IM) (may give IV over 1 to 2 hours) on day 4, 5, or 6; duanorubicin IV on days 1, 8, 15 and 22; and methotrexate IT on days 8 and 29 (and days 15 and 22 for patients with CNS3 disease). GROUP I ARM I COMBINATION CHEMOTHERAPY (CONSOLIDATION CHEMOTHERAPY): Patients receive methotrexate IT on days 1, 8, 15, and 22; cyclophosphamide IV over 30 minutes on days 1 and 29; cytarabine IV over 15-30 minutes or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO on days 1-14 and 29-42; vincristine sulfate IV on days 15, 22, 43 and 50; and pegaspargase IM or IV over 1-2 hours on days 15 and 43. Patients with DS also receive leucovorin calcium PO at 48 and 60 hours after each methotrexate dose. Patients with persistent testicular disease or with DS and testicular disease undergo testicular radiotherapy on days 11-12, 15-19, and 22-26. (DS patients excluded as of 09/29/10.) Patients with intermediate-risk or high-risk disease (CNS1 or CNS2) undergo prophylactic CRT (1,200 cGy/dose) QD on days 15-21 and 22-28. Patients with low-risk disease do not undergo conformal radiation therapy (CRT). Patients with standard risk T-LLy received Arm I, and those with high risk T-LLy were randomized between Arm I and Arm II combination chemotherapy. GROUP I ARM I COMBINATION CHEMOTHERAPY (DELAYED INTENSIFICATION CHEMOTHERAPY): Patients receive vincristine sulfate IV on days 1, 8, 15, 43, and 50; dexamethasone IV or PO BID on days 1-21 (for patients \< 10 years of age) OR on days 1-7 and 15-21 (for patients \>= 10 years of age and for patients with DS); doxorubicin hydrochloride IV on days 1, 8, and 15; pegaspargase IM or IV over 1-2 hours on day 4, 5, OR 6, AND day 43; methotrexate IT on days 1, 29, and 36; cyclophosphamide IV over 30 minutes on day 29; cytarabine IV over 15-30 minutes or SC on days 29-32 and 36-39; and thioguanine PO on days 29-42. Patients with DS also receive leucovorin calcium PO at 48 and 60 hours after each methotrexate dose (DS patients excluded as of 09/29/10). Standard risk T-LLy patients were assigned to Arm I and those with high risk were randomized between Arm I and Arm II. GROUP I ARM I COMBINATION CHEMOTHERAPY (INTERIM MAINTENANCE CHEMOTHERAPY): Patients receive vincristine sulfate IV and escalating doses of methotrexate IV on days 1, 11, 21, 31, and 41; pegaspargase\* IM or IV over 1-2 hours on days 2 and 22; and methotrexate IT on days 1 and 31. Patients with DS also receive leucovorin calcium PO 48 and 60 hours after each methotrexate IT dose (DS patients excluded as of 09/29/10). Note: \*Patients with an allergy to pegaspargase receive Erwinia asparaginase on days 2, 4, 6, 8, 10, 12, 22, 24, 26, 28, 30, and 32. GROUP I ARM I COMBINATION CHEMOTHERAPY (MAINTENANCE CHEMOTHERAPY): Patients receive vincristine sulfate IV on days 1, 29, and 57; prednisone PO BID on days 1-5, 29-33, and 57-61; mercaptopurine PO QD on days 1-84; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; and methotrexate IT on day 1. Treatment repeats every 84 days until the total duration of study treatment is 2 years from the start of interim maintenance therapy (approximately week 119) (for girls with T-ALL), all patients with T-LLy, and 3 years from the start of interim maintenance therapy (approximately week 171) (for boys with T-ALL). GROUP I ARM II COMBINATION CHEMOTHERAPY (CONSOLIDATION CHEMOTHERAPY): Patients receive nelarabine IV over 60 minutes on days 1-5 and 43-47; methotrexate IT on days 15, 22, 57, and 64; cyclophosphamide IV over 30 minutes on days 8 and 50; cytarabine IV over 15-30 minutes or SC on days 8-11, 15-18, 50-53 and 57-60; mercaptopurine PO on days 8-21 and 50-63; vincristine sulfate IV on days 22, 29, 64, and 71; and pegaspargase IM or IV over 1-2 hours on days 22 and 64. Patients with persistent testicular disease or with DS and testicular disease undergo testicular radiotherapy on days 15, 22-26, and 29-33 (DS patients excluded as of 09/29/10). (Patients with intermediate-risk or high-risk disease (CNS1 or CNS2) undergo prophylactic CRT QD on days 22-28 and 29-35. Patients with high risk T-LLy were either randomized to Arm I or Arm II. Patients with T-LLy who failed induction therapy were assigned to Arm II. GROUP I ARM II COMBINATION CHEMOTHERAPY (DELAYED INTENSIFICATION CHEMOTHERAPY): Patients receive vincristine sulfate IV on days 1, 8, 15, and 50; dexamethasone IV or PO BID on days 1-21 (for patients \< 10 years of age) OR on days 1-7 and 15-21 (for patients \>= 10 years of age); doxorubicin hydrochloride IV on days 1, 8, and 15; pegaspargase IM or IV over 1-2 hours on day 4, 5, OR 6 AND day 50; methotrexate IT on days 1, 36, and 43; nelarabine IV over 60 minutes on days 29-33; cyclophosphamide IV over 30 minutes on day 36; cytarabine IV over 15-30 minutes or SC on days 36-39 and 43-46; and thioguanine PO on days 36-49. GROUP I ARM II COMBINATION CHEMOTHERAPY (INTERIM MAINTENANCE CHEMOTHERAPY): Patients receive vincristine sulfate IV and escalating doses of methotrexate IV on days 1, 11, 21, 31, and 41; pegaspargase\* IM or IV over 1-2 hours on days 2 and 22; and methotrexate IT on days 1 and 31. Note: \*Patients with an allergy to pegaspargase receive Erwinia asparaginase on Monday, Wednesday and Friday for two consecutive weeks starting the day of asparaginase substitution. GROUP I ARM II COMBINATION CHEMOTHERAPY (MAINTENANCE CHEMOTHERAPY): Patients receive vincristine sulfate, prednisone, mercaptopurine, methotrexate PO, methotrexate IT, and nelarabine in Cycles 1, 2 and 3. Patients then receive treatment (without nelarabine) as follows: vincristine sulfate, prednisone, mercaptopurine, methotrexate PO, and methotrexate IT as in arm II. Treatment (without nelarabine) repeats every 84 days until the total duration of study treatment is 2 years from the start of interim maintenance therapy (approximately week 121) (for girls with T-ALL), and for those with T-LLY, and 3 years from the start of interim maintenance therapy (approximately week 173) (for boys with T-ALL). GROUP I ARM III COMBINATION CHEMOTHERAPY (CONSOLIDATION CHEMOTHERAPY): Patients receive methotrexate IT on days 1, 8, 15, and 22; cyclophosphamide IV over 30 minutes on days 1 and 29; cytarabine IV over 15-30 minutes or SC on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO on days 1-14 and 29-42; vincristine sulfate IV on days 15, 22, 43 and 50; and pegaspargase IM or IV over 1-2 hours on days 15 and 43. Patients with DS also receive leucovorin calcium PO at 48 and 60 hours after each methotrexate dose. Patients with persistent testicular disease or with DS and testicular disease undergo testicular radiotherapy on days 11-12, 15-19, and 22-26. (DS patients excluded as of 09/29/10.) Patients with intermediate-risk or high-risk disease (CNS1 or CNS2) undergo prophylactic CRT (1,200 cGy/dose) QD on days 15-21 and 22-28. Patients with low-risk disease do not undergo CRT. GROUP I ARM III COMBINATION CHEMOTHERAPY (DELAYED INTENSIFICATION CHEMOTHERAPY): Patients receive vincristine sulfate IV on days 1, 8, 15, 43, and 50; dexamethasone IV or PO BID on days 1-21 (for patients \< 10 years of age) OR on days 1-7 and 15-21 (for patients \>= 10 years of age and for patients with DS); doxorubicin hydrochloride IV on days 1, 8, and 15; pegaspargase IM or IV over 1-2 hours on day 4, 5, OR 6, AND day 43; methotrexate IT on days 1, 29, and 36; cyclophosphamide IV over 30 minutes on day 29; cytarabine IV over 15-30 minutes or SC on days 29-32 and 36-39; and thioguanine PO on days 29-42. Patients with DS also receive leucovorin calcium PO at 48 and 60 hours after each methotrexate dose (DS patients excluded as of 09/29/10). GROUP I ARM III COMBINATION CHEMOTHERAPY (INTERIM MAINTENANCE CHEMOTHERAPY): Patients receive high dose methotrexate (HDMTX) IV over 24 hours and vincristine sulfate IV on days 1, 15, 29, and 43; mercaptopurine PO on days 1-56; and methotrexate IT on days 1 and 29. Beginning 42 hours after the start of HDMTX, patients also receive leucovorin calcium IV or PO once every 6 hours for 3 doses. GROUP I ARM III COMBINATION CHEMOTHERAPY (MAINTENANCE CHEMOTHERAPY): Patients receive vincristine sulfate IV on days 1, 29, and 57; prednisone PO BID on days 1-5, 29-33, and 57-61; mercaptopurine PO QD on days 1-84; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; and methotrexate IT on day 1. Treatment repeats every 84 days until the total duration of study treatment is 2 years from the start of interim maintenance therapy (approximately week 119) (for girls with T-ALL) and all patients with T-LLy, and 3 years from the start of interim maintenance therapy (approximately week 171) (for boys with T-ALL). GROUP I ARM IV COMBINATION CHEMOTHERAPY (CONSOLIDATION CHEMOTHERAPY): Patients receive nelarabine IV over 60 minutes on days 1-5 and 43-47; methotrexate IT on days 15, 22, 57, and 64; cyclophosphamide IV over 30 minutes on days 8 and 50; cytarabine IV over 15-30 minutes or SC on days 8-11, 15-18, 50-53 and 57-60; mercaptopurine PO on days 8-21 and 50-63; vincristine sulfate IV on days 22, 29, 64, and 71; and pegaspargase IM or IV over 1-2 hours on days 22 and 64. (DS patients excluded as of 09/29/10). (Patients with intermediate-risk or high-risk disease (CNS1 or CNS2) undergo prophylactic CRT QD on days 22-28 and 29-35. GROUP I ARM IV COMBINATION CHEMOTHERAPY (DELAYED INTENSIFICATION CHEMOTHERAPY): Patients receive vincristine sulfate IV on days 1, 8, 15, and 50; dexamethasone IV or PO BID on days 1-21 (for patients \< 10 years of age) OR on days 1-7 and 15-21 (for patients \>= 10 years of age); doxorubicin hydrochloride IV on days 1, 8, and 15; pegaspargase IM or IV over 1-2 hours on day 4, 5, OR 6 AND day 50; methotrexate IT on days 1, 36, and 43; nelarabine IV over 60 minutes on days 29-33; cyclophosphamide IV over 30 minutes on day 36; cytarabine IV over 15-30 minutes or SC on days 36-39 and 43-46; and thioguanine PO on days 36-49. GROUP I ARM IV COMBINATION CHEMOTHERAPY (INTERIM MAINTENANCE CHEMOTHERAPY): Patients receive HDMTX IV over 24 hours and vincristine sulfate IV on days 1, 15, 29, and 43; mercaptopurine PO on days 1-56; and methotrexate IT on days 1 and 29. Beginning 42 hours after the start of HDMTX, patients also receive leucovorin calcium IV or PO once every 6 hours for 3 doses. GROUP I ARM IV COMBINATION CHEMOTHERAPY (MAINTENANCE CHEMOTHERAPY): Patients receive vincristine sulfate, prednisone, mercaptopurine, methotrexate PO, methotrexate IT, and nelarabine in Cycles 1, 2 and 3. Patients then receive treatment (without nelarabine) as follows: vincristine sulfate, prednisone, mercaptopurine, methotrexate PO, and methotrexate IT as in arm II. Treatment (without nelarabine) repeats every 84 days until the total duration of study treatment is 2 years from the start of interim maintenance therapy (approximately week 121) (for girls with T-ALL), and for those with T-LLY, and 3 years from the start of interim maintenance therapy (approximately week 173) (for boys with T-ALL). After completion of study therapy, patients are followed periodically for at least 10 years.
Interventions
DRUGAsparaginase
Given IM or IV
DRUGCyclophosphamide
Given IV
DRUGCytarabine
Given IT, IV, or SC
DRUGDaunorubicin Hydrochloride
Given IV
DRUGDexamethasone
Given IV or PO
DRUGDoxorubicin Hydrochloride
Given IV
OTHERLaboratory Biomarker Analysis
Correlative studies
DRUGLeucovorin Calcium
Given PO
DRUGMercaptopurine
Given PO
DRUGMethotrexate
Given IT or PO
DRUGNelarabine
Given IV
DRUGPegaspargase
Given IM or IV
DRUGPrednisone
Given IV or PO
RADIATIONRadiation Therapy
Some patients undergo testicular and/or prophylactic cranial RT
DRUGThioguanine
Given PO
DRUGVincristine Sulfate
Given IV
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 30 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease-free Survival (DFS) for Randomized Nelarabine T-ALL Cohort (Arm I vs. Arm II vs. Arm III vs. Arm IV) | 4 years from randomization at the end of induction | Disease Free Probability where DFS time is defined as time from randomization end of induction to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. |
| Disease-free Survival (DFS) for Randomized Nelarabine T-ALL Cohort (Arm I + Arm III vs. Arm II + Arm IV) | 4 years from randomization at the end of induction | Disease Free Probability where DFS time is defined as time from randomization end of induction to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event |
| Disease-free Survival (DFS) for Randomized Methotrexate T-ALL Cohort (Arm I vs. Arm II vs. Arm III vs. Arm IV) | 4 years from randomization at the end of induction | Disease-free survival defined as time from randomization end of induction to first event (relapse, second malignant neoplasm, remission death) or date of last contact for those who are event-free. |
| Disease-free Survival (DFS) for Randomized Methotrexate T-ALL Cohort (Arm I + Arm II vs. Arm III + Arm IV) | 4 years from randomization at the end of induction | Disease Free Probability where DFS time is defined as time from randomization end of induction to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. |
| Disease-free Survival (DFS) for T-cell Lymphoblastic Lymphoma (T-LLy) Cohort | 4 years from end of induction | Disease Free Probability where DFS time is defined as time from randomization end of induction to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Incidence of CNS Relapse for T-ALL by Risk Group | 4 years from randomization at the end of induction | Cumulative incidence of CNS relapse adjusting for DFS events, was calculated using the method Gray et. al. High risk patients receive cranial radiation and low risk patients receive no cranial radiation. |
Countries
Australia, Canada, New Zealand, Switzerland, United States
Contacts
PRINCIPAL_INVESTIGATORStuart S Winter
Children's Oncology Group
Participant flow
Pre-assignment details
Patients were stratified between the 2 disease groups (T-ALL and T-LLy) for Induction and then risk assigned treatment based upon the patient's response.
Participants by arm
| Arm | Count |
|---|---|
| T-ALL Induction Therapy All patients diagnosed as T-ALL for induction | 1,596 |
| T-LLy Induction Therapy All patients diagnosed as T-LLy for induction | 299 |
| Total | 1,895 |
Baseline characteristics
| Characteristic | T-ALL Induction Therapy | T-LLy Induction Therapy | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 1493 Participants | 268 Participants | 1761 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 103 Participants | 31 Participants | 134 Participants |
| Age, Continuous | 10.05 years STANDARD_DEVIATION 5.3 | 11.13 years STANDARD_DEVIATION 5.8 | 10.22 years STANDARD_DEVIATION 5.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 227 Participants | 45 Participants | 272 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1307 Participants | 244 Participants | 1551 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 62 Participants | 10 Participants | 72 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 6 Participants | 1 Participants | 7 Participants |
| Race (NIH/OMB) Asian | 87 Participants | 11 Participants | 98 Participants |
| Race (NIH/OMB) Black or African American | 204 Participants | 50 Participants | 254 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 12 Participants | 4 Participants | 16 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 165 Participants | 25 Participants | 190 Participants |
| Race (NIH/OMB) White | 1122 Participants | 208 Participants | 1330 Participants |
| Sex: Female, Male Female | 407 Participants | 90 Participants | 497 Participants |
| Sex: Female, Male Male | 1189 Participants | 209 Participants | 1398 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 6 / 1,563 | 39 / 368 | 26 / 372 | 10 / 147 | 45 / 451 | 35 / 219 | 0 / 285 | 8 / 80 | 17 / 143 | 5 / 62 |
| other Total, other adverse events | 983 / 1,563 | 0 / 368 | 357 / 372 | 134 / 147 | 436 / 451 | 197 / 219 | 152 / 285 | 4 / 80 | 140 / 143 | 55 / 62 |
| serious Total, serious adverse events | 25 / 1,563 | 1 / 368 | 18 / 372 | 44 / 147 | 23 / 451 | 66 / 219 | 1 / 285 | 0 / 80 | 10 / 143 | 20 / 62 |
Outcome results
Primary
Disease-free Survival (DFS) for Randomized Methotrexate T-ALL Cohort (Arm I + Arm II vs. Arm III + Arm IV)
Disease Free Probability where DFS time is defined as time from randomization end of induction to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free.
Time frame: 4 years from randomization at the end of induction
Population: Includes subjects randomized to Capizzi Methotrexate versus High-Dose Methotrexate
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ARM I (Combination Chemotherapy) | Disease-free Survival (DFS) for Randomized Methotrexate T-ALL Cohort (Arm I + Arm II vs. Arm III + Arm IV) | 91.45 percent probability |
| ARM II (Combination Chemotherapy) | Disease-free Survival (DFS) for Randomized Methotrexate T-ALL Cohort (Arm I + Arm II vs. Arm III + Arm IV) | 85.78 percent probability |
Primary
Disease-free Survival (DFS) for Randomized Methotrexate T-ALL Cohort (Arm I vs. Arm II vs. Arm III vs. Arm IV)
Disease-free survival defined as time from randomization end of induction to first event (relapse, second malignant neoplasm, remission death) or date of last contact for those who are event-free.
Time frame: 4 years from randomization at the end of induction
Population: Includes only T-cell Acute Lymphoblastic Leukemia (T-ALL) patients randomized to Capizzi Methotrexate (CMTX) versus High-Dose Methotrexate (HDMTX). CNS3 patients non-randomly assigned to HDMTX (Arms III and IV) and Induction failures non-randomly assigned to Arm IV were excluded. T-LLY patients are excluded.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ARM I (Combination Chemotherapy) | Disease-free Survival (DFS) for Randomized Methotrexate T-ALL Cohort (Arm I vs. Arm II vs. Arm III vs. Arm IV) | 91.76 percent probability |
| ARM II (Combination Chemotherapy) | Disease-free Survival (DFS) for Randomized Methotrexate T-ALL Cohort (Arm I vs. Arm II vs. Arm III vs. Arm IV) | 90.53 percent probability |
| ARM III (Combination Chemotherapy) | Disease-free Survival (DFS) for Randomized Methotrexate T-ALL Cohort (Arm I vs. Arm II vs. Arm III vs. Arm IV) | 86.06 percent probability |
| ARM IV (Combination Chemotherapy) | Disease-free Survival (DFS) for Randomized Methotrexate T-ALL Cohort (Arm I vs. Arm II vs. Arm III vs. Arm IV) | 84.89 percent probability |
Primary
Disease-free Survival (DFS) for Randomized Nelarabine T-ALL Cohort (Arm I + Arm III vs. Arm II + Arm IV)
Disease Free Probability where DFS time is defined as time from randomization end of induction to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event
Time frame: 4 years from randomization at the end of induction
Population: Includes subjects randomized to Nelarabine versus No Nelarabine
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ARM I (Combination Chemotherapy) | Disease-free Survival (DFS) for Randomized Nelarabine T-ALL Cohort (Arm I + Arm III vs. Arm II + Arm IV) | 82.96 percent probability |
| ARM II (Combination Chemotherapy) | Disease-free Survival (DFS) for Randomized Nelarabine T-ALL Cohort (Arm I + Arm III vs. Arm II + Arm IV) | 88.30 percent probability |
Primary
Disease-free Survival (DFS) for Randomized Nelarabine T-ALL Cohort (Arm I vs. Arm II vs. Arm III vs. Arm IV)
Disease Free Probability where DFS time is defined as time from randomization end of induction to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free.
Time frame: 4 years from randomization at the end of induction
Population: Includes only T-cell Acute Lymphoblastic Leukemia (T-ALL) patients randomized to Nelarabine versus No Nelarabine. T-LLY patients are excluded from this analysis. Induction failures non-randomly assigned to Arm IV were excluded from this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ARM I (Combination Chemotherapy) | Disease-free Survival (DFS) for Randomized Nelarabine T-ALL Cohort (Arm I vs. Arm II vs. Arm III vs. Arm IV) | 89.01 percent probability |
| ARM II (Combination Chemotherapy) | Disease-free Survival (DFS) for Randomized Nelarabine T-ALL Cohort (Arm I vs. Arm II vs. Arm III vs. Arm IV) | 90.53 percent probability |
| ARM III (Combination Chemotherapy) | Disease-free Survival (DFS) for Randomized Nelarabine T-ALL Cohort (Arm I vs. Arm II vs. Arm III vs. Arm IV) | 78.07 percent probability |
| ARM IV (Combination Chemotherapy) | Disease-free Survival (DFS) for Randomized Nelarabine T-ALL Cohort (Arm I vs. Arm II vs. Arm III vs. Arm IV) | 86.46 percent probability |
Primary
Disease-free Survival (DFS) for T-cell Lymphoblastic Lymphoma (T-LLy) Cohort
Disease Free Probability where DFS time is defined as time from randomization end of induction to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free.
Time frame: 4 years from end of induction
Population: Includes T-cell lymphoblastic lymphoma (T-LLy) patients that are standard risk, high risk and induction failures. All Standard risk T-LLy patients only received Arm I. Induction failures were assigned to Arm II.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ARM I (Combination Chemotherapy) | Disease-free Survival (DFS) for T-cell Lymphoblastic Lymphoma (T-LLy) Cohort | Standard Risk | 87.4 percent probability |
| ARM I (Combination Chemotherapy) | Disease-free Survival (DFS) for T-cell Lymphoblastic Lymphoma (T-LLy) Cohort | High Risk | 85.1 percent probability |
| ARM II (Combination Chemotherapy) | Disease-free Survival (DFS) for T-cell Lymphoblastic Lymphoma (T-LLy) Cohort | High Risk | 85.0 percent probability |
| ARM II (Combination Chemotherapy) | Disease-free Survival (DFS) for T-cell Lymphoblastic Lymphoma (T-LLy) Cohort | Induction Failure | 100 percent probability |
Secondary
Cumulative Incidence of CNS Relapse for T-ALL by Risk Group
Cumulative incidence of CNS relapse adjusting for DFS events, was calculated using the method Gray et. al. High risk patients receive cranial radiation and low risk patients receive no cranial radiation.
Time frame: 4 years from randomization at the end of induction
Population: Includes only low risk, intermediate risk and high risk T-cell Acute Lymphoblastic Leukemia (T-ALL) subjects. There were no low risk participants on Arm II and Arm IV. Patients with CNS3, and Induction Failures are excluded from this analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ARM I (Combination Chemotherapy) | Cumulative Incidence of CNS Relapse for T-ALL by Risk Group | Intermediate Risk | 1.16 percent probability |
| ARM I (Combination Chemotherapy) | Cumulative Incidence of CNS Relapse for T-ALL by Risk Group | High Risk | 3.64 percent probability |
| ARM I (Combination Chemotherapy) | Cumulative Incidence of CNS Relapse for T-ALL by Risk Group | Low Risk | 1.85 percent probability |
| ARM II (Combination Chemotherapy) | Cumulative Incidence of CNS Relapse for T-ALL by Risk Group | High Risk | 0 percent probability |
| ARM II (Combination Chemotherapy) | Cumulative Incidence of CNS Relapse for T-ALL by Risk Group | Intermediate Risk | 1.08 percent probability |
| ARM III (Combination Chemotherapy) | Cumulative Incidence of CNS Relapse for T-ALL by Risk Group | Intermediate Risk | 9.1 percent probability |
| ARM III (Combination Chemotherapy) | Cumulative Incidence of CNS Relapse for T-ALL by Risk Group | High Risk | 6.52 percent probability |
| ARM III (Combination Chemotherapy) | Cumulative Incidence of CNS Relapse for T-ALL by Risk Group | Low Risk | 1.92 percent probability |
| ARM IV (Combination Chemotherapy) | Cumulative Incidence of CNS Relapse for T-ALL by Risk Group | High Risk | 3.45 percent probability |
| ARM IV (Combination Chemotherapy) | Cumulative Incidence of CNS Relapse for T-ALL by Risk Group | Intermediate Risk | 0.85 percent probability |