Spots Global Cancer Trial Database for A Study of Children With Refractory or Relapsed ALL

Study Description

Brief Summary: The main purpose of this study is to find out which form of asparaginase (the native E. coli/Erwinia) or PEG-asparaginase) is more effective during induction treatment for children with acute lymphoblastic leukemia that has come back after treatment (relapsed) or is resistant to treatment (refractory)

Detailed Description: The present protocol will compare the biologic effects of PEG-asparaginase vs native-forms of asparaginase in a randomized trial using the same dosages and schedules used in the POG 9411 study. Comprehensive studies, including the measurement of antibodies and asparagine levels as well as the pharmacokinetics of L-asparaginase, will be performed. This protocol will also study the changes in topoisomerase I and topoisomerase II levels and the fractions of topoisomerase I/II translocations in malignant lymphoblasts after upfront window topotecan therapy, and correlate oncolytic response with these changes. Secondary objectives include: * To compare changes in asparagine levels 28 days after initiation of treatment with asparaginase between the two groups. * To estimate the pharmacokinetics of L-asparaginase, compare the pharmacokinetics between the two groups of patients, and correlate the pharmacokinetics with the development of antibody to asparaginase and depletion of asparagine. * To measure the pharmacokinetics and pharmacodynamics of topotecan in patients with recurrent acute lymphoblastic leukemia * To determine whether the frequency of recombinogenesis in lymphocytes is increased during or after etoposide therapy relative to the pre-therapy level, and to explore whether etoposide pharmacokinetics are related to the Day 7 or post-therapy level of recombinogenesis. Detailed Description of Treatment Plan WINDOW Topotecan 2.4 mg/m2 ; IV over 30 min in 5 doses Days 1-5 STANDARD INDUCTION Dexamethasone 6 mg/m2/day orally Days 8-35 Vincristine 1.5 mg/m2 (max 2.0 mg) days 8, 15, 22, 29 RANDOMIZE E. coli asparaginase 10,000 U/m2/day IM (or Erwinia if previous allergy to E. coli) Days 8, 11, 13, 15, 18, 20, 22, 25, 27, 29, 32, 34 OR PEG-Asparaginase 2500 U/m2/day IM Days 8, 15, 22, 29 ITHMA Days 8, 22, 36 CONSOLIDATION Fludarabine: 15 mg/m2 IV over 30 min; days 1,2,3,4 Ara-C: 2 g/m2 IV days 1,2,3,4 Patients who achieve remission on R16 induction or consolidation may be eligible for either a matched sibling or a fully matched/one-antigen-mismatched unrelated donor transplant For patients not undergoing bone marrow transplant: SECONDARY CONSOLIDATION VP 16: 50 mg/m2 PO qd for 14 days. Vincristine: 1.5 mg/m2 (max 2.0 mg) IV; days 1, 8. IT MHA day 1 CONTINUATION CHEMOTHERAPY Cycle 1: Cyclophosphamide 1 g/m2 IV on days 1 and 2 Vincristine 1.5 mg/m2 IV on day 1 (max 2.0 mg) Cycle 2: VP-16 50 mg/m2 day PO daily x 14 days Decadron 6 mg/m2 PO daily ) TID x 14 days Vincristine 1.5 mg/m2 IV (max 2 mg) on days 1 and 8. Cycle 3: HD MTX 5 gm/m2 continuous infusion over 24 hrs E. coli Asparaginase 10,000 U/m2/dose IM qod x3 or PEG Asparaginase 2500 U/m2/dose IM x 1 (maintain same randomization for Asparaginase preparation as during induction) Cycle 4: High Dose Ara-C 2 g/m2/dose IV over 2 hrs q 12 hrs x 3 doses.\[Total dose 6 gm/m2\] Idarubicin 12 mg/m2 IV over 30 min X 1 \[after completion of first dose of Ara-C\] IT MHA on day 1 prior to the HDARA-C (dose of ITMHA is age adjusted as outlined in section 7.3) STANDARD CONTINUATION CHEMOTHERAPY Patients will receive 4-week rotational cycles of chemotherapy with the following pairs of drugs for total treatment duration of 17 months. Week #1 Cyclophosphamide (300 mg/m2 IV) + VCR (1.5 mg/m2 IV; max 2 mg). Week #2 VM26 (200 mg/m2 IV) + Ara C (300 mg/m2 IV). Week #3 MTX (MTX should be given IM or as a 2 hr IV infusion if the patient has had previous cranial iradiation) (40 mg/m2 IV/IM) + 6 MP (75 mg/m2 PO q HS x 7) Week #4 MTX (MTX should be given IM or as a 2 hr IV infusion if the patient has had previous cranial irradiation)(40 mg/m2 IV/IM) + 6 MP (75 mg/m2 PO q HS x 7) IT MHA: Given every 8 weeks throughout standard continuation chemotherapy for patients with CNS 1 status Given every 4 weeks for patients with CNS 2/3 status who will receive CSI at the end of chemotherapy

Keywords

Eligibility

Minimum Age:

Eligible Ages: CHILD, ADULT

Sex: ALL

Healthy Volunteers: No

Locations

Contact Details

Useful links and downloads for this trial