AALL07P1, A Phase II Pilot Trial of Bortezomib (PS-341, Velcade, IND# 58,443) in Combination with Intensive Re-Induction Therapy for Children with Relapsed Acute Lymphoblastic Leukemia (ALL) and Lymphoblastic Lymphoma (LL) A Groupwide Pilot Study
This is a single arm study using bortezomib in combination with iintensive induction therapy.
The primary objectives are to estimate the toxicity, second complete remission (CR2) rate at the end of Block 1 therapy, 4-month event-free survival (EFS) of the above regimen, and to determine bortezomib pharmacokinetics in patients receiving the combination regimen.
All eligible participants will receive standard COG re-induction therapy over the course of about 15 weeks. The re-induction regimen involves a combination of different chemotherapy drugs and the treatment plan is split into 3 blocks of 5 weeks. All participants will receive the experimental drug bortezomib on days 1, 4, 8, and 11 of Block 1 and days 1, 4, and 8 of Block 2 of therapy. The dose of bortezomib will be 1.3 mg/m2. Bortezomib will be administered through a needle or tubing inserted into a vein over 3 to 5 seconds.
Patients must be >= 1 year of age and <= 31 years of age (< 18 years of age at this institution) at the time of study enrollment.
- Pre-B ALL in first early (< 36 months from diagnosis) isolated bone marrow (BM) or combined BM/extramedullary relapse; or - T-cell ALL in first isolated BM or combined relapse; or - T-LL in first relapse
Patients with leukemia must have had histologic verification of the malignancy at relapse, including immunophenotyping to confirm diagnosis.
Patients with lymphoblastic lymphoma must have measurable disease documented by clinical, radiographic, or histologic criteria. Patients must have relapsed or become refractory to conventional therapy.
Patients must have a performance status corresponding to ECOG scores of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients <= 16 years of age.
Patients who relapse while receiving standard ALL maintenance chemotherapy will not be required to have a waiting period before entry onto this study.
Patients who relapse on therapy other than standard ALL maintenance therapy must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
Organ Function Requirements:
All patients must have adequate renal, liver, cardiac, pulmonary, CNS, and peripheral nervous system function.