Bortezomib and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia
- Conditions
- Recurrent Adult Acute Lymphoblastic Leukemia (ALL)Ph-positive Adult Acute Lymphoblastic Leukemia (ALL)B-cell Adult Acute Lymphoblastic Leukemia (ALL)T-cell Adult Acute Lymphoblastic Leukemia (ALL)
- Interventions
- Registration Number
- NCT01769209
- Lead Sponsor
- Stanford University
- Brief Summary
This study evaluates the value of bortezomib in combination with specified chemotherapies for the treatment of patients with relapsed or refractory acute lymphoblastic leukemia. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
- Detailed Description
PRIMARY OBJECTIVE:
Determine the response rate of bortezomib in combination with a chemotherapy backbone of doxorubicin (doxorubicin hydrochloride), vincristine (vincristine sulfate), PEG-asparaginase (pegaspargase), and dexamethasone in patients with relapsed/refractory acute lymphoblastic leukemia.
SECONDARY OBJECTIVES:
* Estimate the rate of complete response (CR) and CR with incomplete platelet recovery (CRp) on Day 29 after re-induction.
* Determine progression-free survival (PFS) at 2 years after re-induction.
* Determine failure-free survival (FFS) at 1 year after re-induction.
* Overall survival (OS) at 1 year after re-induction.
* Assess safety and tolerability of the study drug.
* Determine whether bortezomib induces reactive oxygen species (ROS) in circulating acute lymphoblastic leukemia (ALL) blast cells.
OUTLINE:
Patients receive bortezomib subcutaneously (SC) on Days 1, 4, 8, and 11; doxorubicin hydrochloride intravenously (IV) on day 1; pegaspargase IV or intramuscularly (IM) on Days 5 and 22; vincristine sulfate IV on days 1, 8, 15, and 22; dexamethasone orally (PO) daily on Days 1 to 14; cytarabine intrathecally (IT) on Day 1 and methotrexate intrathecally (IT) on Day 15. Patients with central nervous system disease receive intrathecal treatment per investigator's discretion.
Participants are followed up every 3 months for up to 2 years after completion of study treatment.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 18
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Bortezomib + Chemotherapy Vincristine sulfate Patients receive bortezomib on Days 1, 4, 8, and 11; doxorubicin hydrochloride on Day 1; PEG-asparaginase on Days 5 and 22; vincristine sulfate on Days 1, 8, 15, and 22; dexamethasone daily on Days 1 to 14; cytarabine on Day 1, and methotrexate on Day 15. Bortezomib + Chemotherapy Doxorubicin hydrochloride (HCl) Patients receive bortezomib on Days 1, 4, 8, and 11; doxorubicin hydrochloride on Day 1; PEG-asparaginase on Days 5 and 22; vincristine sulfate on Days 1, 8, 15, and 22; dexamethasone daily on Days 1 to 14; cytarabine on Day 1, and methotrexate on Day 15. Bortezomib + Chemotherapy Bortezomib Patients receive bortezomib on Days 1, 4, 8, and 11; doxorubicin hydrochloride on Day 1; PEG-asparaginase on Days 5 and 22; vincristine sulfate on Days 1, 8, 15, and 22; dexamethasone daily on Days 1 to 14; cytarabine on Day 1, and methotrexate on Day 15. Bortezomib + Chemotherapy PEG-Asparaginase Patients receive bortezomib on Days 1, 4, 8, and 11; doxorubicin hydrochloride on Day 1; PEG-asparaginase on Days 5 and 22; vincristine sulfate on Days 1, 8, 15, and 22; dexamethasone daily on Days 1 to 14; cytarabine on Day 1, and methotrexate on Day 15. Bortezomib + Chemotherapy Cytarabine Patients receive bortezomib on Days 1, 4, 8, and 11; doxorubicin hydrochloride on Day 1; PEG-asparaginase on Days 5 and 22; vincristine sulfate on Days 1, 8, 15, and 22; dexamethasone daily on Days 1 to 14; cytarabine on Day 1, and methotrexate on Day 15. Bortezomib + Chemotherapy Dexamethasone Patients receive bortezomib on Days 1, 4, 8, and 11; doxorubicin hydrochloride on Day 1; PEG-asparaginase on Days 5 and 22; vincristine sulfate on Days 1, 8, 15, and 22; dexamethasone daily on Days 1 to 14; cytarabine on Day 1, and methotrexate on Day 15. Bortezomib + Chemotherapy Methotrexate Patients receive bortezomib on Days 1, 4, 8, and 11; doxorubicin hydrochloride on Day 1; PEG-asparaginase on Days 5 and 22; vincristine sulfate on Days 1, 8, 15, and 22; dexamethasone daily on Days 1 to 14; cytarabine on Day 1, and methotrexate on Day 15.
- Primary Outcome Measures
Name Time Method Response Rate (RR) Day 29 Response Rate (RR) was determined as the sum of complete response (CR) and partial response (PR). Due to overlap, "complete response rate without platelet recovery" (CRp) is not included in Response Rate (RR). The outcome is reported as the total number without dispersion.
* CR = No circulating blasts or extramedullary disease; trilineage hematopoiesis; absolute neutrophil count (ANC) \> 1,000/microliter; platelets \> 100,000/microliter; \< 5% blasts in bone marrow.
* CRp = Meets all criteria for CR except platelet count.
* PR = Meets all criteria for CR except bone marrow contains 5 to 25% leukemia cells.
- Secondary Outcome Measures
Name Time Method Failure-free Survival (FFS) 1 year Failure-free survival (FFS) was assessed as survival without progression or the addition of another systemic therapy, at or within 2 years. The outcome is reported as the number (without dispersion) of the participants alive without progression. Progression is defined below.
Progression = More than 25% increase in circulating and/or bone marrow blasts, or the development of extramedullary disease.Complete Response Without Platelet Recovery (CRp) Day 29 Complete response without platelet recovery (CR) was determined as the number of participants who achieved CRp by Day 29 after induction treatment. The outcome is reported as the total number without dispersion. The outcome reflects only those subjects that meet all complete response (CR) criteria except platelet count; participants that meet all criteria including platelet count are not included in this outcome. CR and CRp are defined below.
* CR =.No circulating blasts or extramedullary disease; trilineage hematopoiesis; absolute neutrophil count (ANC) \> 1,000/microliter; platelets \> 100,000/microliter; \< 5% blasts in bone marrow.
* CRp = Meets all criteria for CR except platelet count.Progression-free Survival (PFS) 2 years Progression-free survival (PFS) was assessed as survival without progression at 2 years. The outcome is reported as the number (without dispersion) of the participants alive without progression.
Progression = More than 25% increase in circulating and/or bone marrow blasts, or the development of extramedullary disease.Complete Response (CR) Day 29 Complete response (CR) was determined the number of participants who achieved CR by Day 29 after induction treatment. The outcome is reported as the total number without dispersion. CR is defined as:
* CR = No circulating blasts or extramedullary disease; trilineage hematopoiesis; absolute neutrophil count (ANC) \> 1,000/microliter; platelets \> 100,000/microliter; \< 5% blasts in bone marrow.
* Not CR = All statuses and conditions if less than or not as defined.Induction of Reactive Oxygen Species (ROS) 2 years Circulating acute lymphoblastic leukemia (ALL) blast cells were to be evaluated for the presence of reactive oxygen species (ROS).
Overall Survival (OS) 2 years Overall survival (OS) was assessed as participants remaining alive 2 years after induction therapy. The outcome is reported as the number of participants (without dispersion).
Related Adverse Events (Grade 3, 4, 5) 45 days Toxicity was assessed as related grade 3, 4, or 5 adverse events (AEs) per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03. The outcome is reported as the total numbers of events (without dispersion) by CTCAE Body System, and whether the event was a hematologic toxicity or non-hematologic toxicity.
Trial Locations
- Locations (1)
Stanford University, School of Medicine
🇺🇸Stanford, California, United States