Clinical trial NCT00440726
Conditions: Acute Lymphoblastic Leukemia
Keywords: Acute Lymphoblastic Leukemia Pediatrics Relapsed Recurrence Bortezomib Velcade Therapeutic Advances in Childhood Leukemia Investigational Childhood ALL Relapsed ALL Refractory ALL Relapsed pediatric ALL Refractory pediatric ALL TACL Recurrent Pediatric ALL
Sponsor: Therapeutic Advances in Childhood Leukemia Consortium
Start date: 2006-08-04; Completion date: 2011-02-26
Enrollment: 31 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
This is a Phase I/II study of a drug called bortezomib given in combination with chemotherapy drugs used to treat acute lymphoblastic leukemia (ALL) that has come back (recurred). Bortezomib is a drug that has been approved by the Food and Drug Administration (FDA) for treating adults with multiple myeloma which is a type of blood cancer. Bortezomib has been shown to cause cancer cells to die in studies done on animals (mice). Studies have been done that have shown that some adults and children with cancer have shown a response to bortezomib when it is used alone. Studies have also been done in adults to evaluate the dose of bortezomib that can be safely given in combination with other chemotherapy drugs.

Detailed description:
All patients will receive 1 course of chemotherapy unless medical complications prevent the administration of some of the drugs. Treatment will last about 1 month.

Treatment on this study will consist of a combination of 7 anti-cancer medications. The 7 anti-cancer medicines are bortezomib, vincristine, dexamethasone, PEG-asparaginase, doxorubicin, cytarabine (Ara-C), and methotrexate (MTX).

If you are in the Phase I portion of this study, you will be given an assigned dose of bortezomib. The dose of bortezomib will be based on doses given in previous studies done with adults and children. At each dose level of bortezomib, between 3 and 6 children will receive bortezomib in combination with chemotherapy. If the side effects are not too severe, the next group of children will receive a higher dose. The dose will continue to be increased until we find the dose that causes serious side effects. Your dose of bortezomib will not be increased. If you have bad side effects, your dose may be decreased.

The dose used during the Phase 2 part of this study will be determined by the outcome of the Phase I study. The highest dose used in Phase I that was tolerated without serious side effects will be the one used in Phase 2.

Arms: arm 1: Intervention: Bortezomib with chemotherapy (dexamethasone, PEG-asparaginase, doxorubicin, cytarabine, methotrexate, and vincristine) and Triple IT therapy for patients who are CNS 2 or 3 at study entry. 3+3 escalation design. arm 2: Intervention: Bortezomib with chemotherapy (dexamethasone, PEG-asparaginase, doxorubicin, cytarabine, methotrexate, and vincristine) and Triple IT therapy for patients who are CNS 2 or 3 at study entry. Patients receive bortezomib at maximum tolerated dose (as established in the Phase 1 portion of the study) and are assessed for response and toxicity.
Interventions: intervention 1: Bortezomib intervention 2: Dexamethasone intervention 3: PEG-asparaginase intervention 4: Doxorubicin intervention 5: Cytarabine intervention 6: Methotrexate intervention 7: Vincristine intervention 8: Triple IT Therapy
Intervention descriptions: intervention 1: Intravenous on days 1, 4, 8 and 11. Dose assigned at study entry. intervention 2: 10 mg/m2/day divided BID, oral administration for 14 days. intervention 3: 2500 IU/m2/day, intramuscular injection on Days 2, 8, 15 and 22 intervention 4: 60 mg/m2/day IV over 15 minutes on Day 1 intervention 5: Given intrathecally on Day 1 of course 1 at the dose defined by age below.

* 30 mg for patients age 1-1.99
* 50 mg for patients age 2-2.99
* 70 mg for patients \>3 years of age intervention 6: Given intrathecally to all patients who are CNS 1 at study entry on Day 15 at the dose defined by age below.

* 8 mg for patients age 1-1.99
* 10 mg for patients age 2-2.99
* 12 mg for patients 3-8.99 years of age
* 15 mg for patients \>9 years of age intervention 7: 1.5 mg/m2/dose IV push (maximum single dose 2 mg) on Days 1, 8, 15 and 22. intervention 8: Triple IT therapy will be given intrathecally on Day 8, 15, and 22 for patients who are CNS 2 and CNS 3 at study entry. Regimen/dosing as follows:

Methotrexate-

* \<2 years: 8 mg
* 2 - \<3 y: 10 mg
* 3 - \<9 y: 12 mg
* \>=9 y: 15 mg

Cytarabine:

* \<2 years: 16 mg
* 2 - \<3 y: 20 mg
* 3 - \<9 y: 24 mg
* \>=9 y: 30 mg

Hydrocortisone:

* \<2 years: 8 mg
* 2 - \<3 y: 10 mg
* 3 - \<9 y: 12 mg
* \>=9 y: 15 mg

Protocol documents: