Acute Lymphoblastic Leukemia
Conditions
Keywords
Acute Lymphoblastic Leukemia, High-Risk (HR), Philadelphia Chromosome-Negative
Brief summary
Current therapeutic protocols for adult ALL consider MRD together with the baseline risk factors (age, WBC count, immunophenotype, cytogenetics) and speed in response to therapy for treatment decisions. On the other hand, the systematic use of allogeneic SCT for all adult patients (pts) with Ph- HR-ALL is still a matter of debate. The aim of the prospective study ALL-AR-03 from the Spanish PETHEMA Group was to evaluate the response to a differentiated therapy (chemotherapy or allogeneic SCT) according to early bone marrow blast clearance and MRD levels (assessed by cytofluorometry at the end of induction and consolidation therapy) in HR Ph- adult ALL patients.
Detailed description
HR ALL included one or more of the following baseline parameters: age 30-60 yr, WBC count \>25x109/L and 11q23 or MLL rearrangements. Induction therapy included vincristine, prednisone and daunorubicin for 4 weeks. In pts with slow cytologic response to therapy (≥10% blasts in bone marrow assessed on d14) intensified induction with high dose ARA-C and mitoxantrone was administered. Early consolidation therapy included 3 cycles with rotating cytotoxic drugs including high-dose methotrexate, high-dose ARA-C and high-dose asparaginase. Pts. with slow cytologic response on d14 or MRD level \>0.05% after consolidation were assigned to allogeneic SCT (related or unrelated) and those with standard cytologic response on d14 and MRD level \<0.05% after consolidation received 3 additional cycles of delayed consolidation (identical to those of early consolidation) followed by maintenance therapy up to 2yr in CR.
Interventions
DRUGVincristine
Vincristine (VCR): 1.5 mg/m2 (max 2 mg) IV d 1, 8, 15, 22 in induction VCR 2 mg, IV, d 1,8 in consolidation (cycle 1, 2)
DRUGDaunorubicin
Daunorubicin (DNR): 60 mg/m2 IV d 1, 8, 15, 22
DRUGPrednisone
Prednisone (PDN): 60 mg/m2/d IV or PO, d 1-28
DRUGMitoxantrone
Mitoxantrone:12 mg/m2, IV d 15-17 in induction 12 mg/m2, IV,d 5 in cycle 2 consolidation
ARA-C 2,000 mg/m2/12h IV, d18,19 (4 doses) in induction
DRUGDexamethasone
Dexamethasone 20 mg/m2,IV, d 1-5,10 mg/m2,IV, d 6 and 5 mg/m2,IV, d 7 in Consolidation (3 cycles)
DRUGMethotrexate (MTX)
Methotrexate (MTX)3 g/m2,IV, d1 (24h)in consolidation, cycles 1 and 2 MTX (15 mg/m2/wk, IM)in maintenance MTX 15 mg, IT
DRUGCytarabine
Cytarabine 2g/m2/12h, IV d5 in cycle 1 consolidation Cytarabine 2g/m2/12h, IV d 1,2 in cycle 3 consolidation Cytarabine 30 mg, intrathecal
DRUGASP
ASP 25,000 IU/m2, IV, d5 in consolidation (cycle 1, 2, 3)
DRUGMercaptopurine
Mercaptopurine 100 mg/m2, PO, d 1-5 in consolidation
DRUGTeniposide
Teniposide 150 mg/m2, IV d 3,4 in consolidation cycle 3
DRUGHydrocortisone
Hydrocortisone 20 mg, IT d 1, 28, 49, 77, 105, 175, 203, 231, 259,287, 311 intrathecal
Sponsors
PETHEMA Foundation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* High risk ALL adult patients (age\> 15 years)no treated previously * High-risk ALL: * One or more of the following: * Age 30-60 yr. * WBC count \>25x109/L * 11q23 or ALL1/AF4 * Very high-risk ALL: * HR ALL and one or the following: * Slow cytologic response (\>10% blasts in BM on d14 of induction therapy). * MRD\>0.05% (by flow cytometry) at the end of consolidation
Exclusion criteria
* L3 ALL or B mature(sIg +) or t(8;14), t(2;8), t(8;22). * ALL Ph (BCR/ABL) positive. * Bifenotipics ALL as EGIL criteria. * Indifferentiated ALL. * Patients with cardiac pathology * Patients with chronic liver disease in activity fase * Pulmonary disease * Renal insufficiency not due to ALL * Neurological disorders not due to ALL * PS (grades 3 and 4) not due to ALL.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the response to a differentiated therapy (chemotherapy or allogeneic SCT) according to early bone marrow blast clearance and MRD levels in HR Ph- adult ALL patients. | 2 years |
Countries
Spain
Outcome results
None listed