Bortezomib With Chemotherapy for Relapsed Pediatric Acute Lymphoblastic Leukemia (ALL)
- Conditions
- Acute Lymphoblastic Leukemia
- Interventions
- Registration Number
- NCT00440726
- Lead Sponsor
- Therapeutic Advances in Childhood Leukemia Consortium
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 31
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Ph 2 Efficacy and Safety Triple IT Therapy 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. Ph 1 Dose Escalation Triple IT Therapy 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. Ph 1 Dose Escalation Dexamethasone 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. Ph 1 Dose Escalation Bortezomib 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. Ph 1 Dose Escalation PEG-asparaginase 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. Ph 1 Dose Escalation Doxorubicin 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. Ph 1 Dose Escalation Cytarabine 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. Ph 1 Dose Escalation Methotrexate 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. Ph 1 Dose Escalation Vincristine 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. Ph 2 Efficacy and Safety Bortezomib 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. Ph 2 Efficacy and Safety Dexamethasone 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. Ph 2 Efficacy and Safety PEG-asparaginase 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. Ph 2 Efficacy and Safety Methotrexate 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. Ph 2 Efficacy and Safety Doxorubicin 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. Ph 2 Efficacy and Safety Cytarabine 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. Ph 2 Efficacy and Safety Vincristine 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.
- Primary Outcome Measures
Name Time Method Occurrence of a Dose-Limiting Toxicity (Phase 1) Beginning with the first dose of investigational product until 30 days following the last dose of bortezomib Toxicity will be graded using the CTCAE criteria, version 3.0. Dose-limiting toxicity will be defined as any of the following events that are deemed by the investigator as possibly, probably or definitely attributable to bortezomib: Grade 3 or 4 Sensory Neuropathy; Grade 3 or 4 Neuropathic pain (Neuralgia or peripheral nerve) lasting longer than 24 hours despite medical intervention; Marrow hypoplasia, which continues 6 weeks from the start of each course (less than 10% cellularity); and Grade 4 Non-Hematologic Toxicity excluding the following: Infection (septic shock, typhlitis), Fever/Neutropenia, Fatigue, Electrolyte abnormalities, Hyper/Hypoglycemia, Nausea or Vomiting, AST/ALT/Bilirubin elevations that return to grade 1 by the time of the next course.
Achievement of Complete Remission (CR) Day 29 of Course 1 * Complete Remission (CR): M1 (\< 5% blasts) BM with no evidence of circulating blasts or extramedullary disease and with recovery of peripheral counts (ANC\>750/uL and platelet count \>75 000/uL);
* Complete Remission without Platelet Recovery (CRp): M1 BM with no circulating blasts or extramedullary disease and recovery of ANC (\>750/uL) but insufficient recovery of platelets (\<75 000/uL).
* Partial Remission (PR): the disappearance of circulating blasts and achievement of M2 (5%-25% blasts) marrow status, without new sites of extramedullary disease, and with recovery of ANC (\>750/uL).
* Stable disease (SD): not satisfying the criterion for progressive disease (PD), or a recovery of ANC (\>750/uL) but fails to qualify for CR, CRp, or PR.
* Progressive Disease (PD): increase of at least 25% in the absolute number of circulating leukemia cells, development of new sites of extramedullary disease, or other lab or clinical evidence of PD, with or without recovery of ANC or platelets.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (24)
Sick Kids
🇨🇦Toronto, Ontario, Canada
Childrens Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Children's Healthcare of Atlanta
🇺🇸Atlanta, Georgia, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
Johns Hopkins / Sydney Kimmel Cancer Center
🇺🇸Baltimore, Maryland, United States
Dana Farber Cancer Center
🇺🇸Boston, Massachusetts, United States
Childrens Hospital & Clinics of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
Stanford University Medical Center
🇺🇸Palo Alto, California, United States
Miller Children's Hospital
🇺🇸Long Beach, California, United States
City of Hope
🇺🇸Duarte, California, United States
University of Miami Cancer Center
🇺🇸Miami, Florida, United States
Children's Hospital & Research Center Oakland
🇺🇸Oakland, California, United States
UCSF School of Medicine
🇺🇸San Francisco, California, United States
Sydney Children's Hospital
🇦🇺Randwick, New South Wales, Australia
The Children's Hospital at Westmead
🇦🇺Westmead, New South Wales, Australia
Universidade Federale de Sao Paulo/Hospital Sao Paulo
🇧🇷São Paulo, Brazil
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
C.S. Mott Children's Hospital
🇺🇸Ann Arbor, Michigan, United States
Children's Hospital New York-Presbyterian
🇺🇸New York, New York, United States
Primary Children's Hospital
🇺🇸Salt Lake City, Utah, United States
Levine Children's Hospital
🇺🇸Charlotte, North Carolina, United States
New York University Medical Center
🇺🇸New York, New York, United States