Bortezomib and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia
B-cell Adult Acute Lymphoblastic Leukemia
Ph Positive Adult Acute Lymphoblastic Leukemia
Recurrent Adult Acute Lymphoblastic Leukemia
T-cell Adult Acute Lymphoblastic Leukemia
Drug: doxorubicin hydrochloride
Drug: vincristine sulfate
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study of Subcutaneous Bortezomib in Combination With Chemotherapy in Relapsed/Refractory Adult Acute Lymphoblastic Leukemia|
- CR rate [ Time Frame: On day 29 at the end of induction therapy ] [ Designated as safety issue: No ]Response rates will be evaluated and accompanied by 95% confidence intervals using the binomial distribution. Response rate by categories will be calculated with 95% confidence intervals.
- Progression-free survival (PFS) [ Time Frame: From the start of treatment to disease progression or death, whichever comes first, assessed up to 2 years ] [ Designated as safety issue: No ]Analyzed using Kaplan-Meier survival analysis and accompanied with 95% confidence interval.
- CR and CRp rate after re-induction [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]Compared to a historical baseline.
- Failure-free survival (FFS) [ Time Frame: At 1 year ] [ Designated as safety issue: No ]Analyzed by the Kaplan Meier method. Compared to a historical baseline.
- Survival percent [ Time Frame: At 1 year ] [ Designated as safety issue: No ]Compared to a historical baseline.
- Incidence of adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 45 days after completion of treatment ] [ Designated as safety issue: Yes ]Toxicity profile will be presented by rate of overall toxicity and rates of grade 3 or 4 toxicities analyzed separately and combined. Adverse events will be summarized and accompanied by 95% confidence intervals using binomial distribution.
|Study Start Date:||March 2013|
|Estimated Study Completion Date:||March 2017|
|Estimated Primary Completion Date:||March 2016 (Final data collection date for primary outcome measure)|
Experimental: Treatment (bortezomib, chemotherapy)
Patients receive bortezomib SC on days 1, 4, 8, and 11; doxorubicin hydrochloride IV on day 1; pegaspargase IV or IM on days 5 and 22; vincristine sulfate IV on days 1, 8, 15, and 22; dexamethasone PO daily on days 1-14; cytarabine IT on day 1 and methotrexate IT on day 15. Patients with central nervous system disease receive intrathecal treatment per investigator's discretion.
Other Names:Drug: doxorubicin hydrochloride
Other Names:Drug: pegaspargase
Given IV or IM
Other Names:Drug: vincristine sulfate
Other Names:Drug: dexamethasone
Other Names:Drug: cytarabine
Other Names:Drug: methotrexate
Other Name: MTX; amethopterin
I. 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.
I. Determine progression free survival. II. Estimate the rate of complete response (CR) and CR with incomplete platelet recovery (CRp) after this re-induction compared to a historical baseline.
III. Estimate failure-free survival (FFS) and survival percent at 1 year compared to a historical baseline.
IV. Assess safety and tolerability of the study drug. V. Determine whether bortezomib induces reactive oxygen species (ROS) in circulating acute lymphoblastic leukemia (ALL) blast cells.
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 1-14; 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.
After completion of study treatment, patients are followed up every 3 months for up to 2 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01769209
|United States, California|
|Stanford, California, United States, 94305|
|Contact: Ying Hao, PhD 650-723-0646 firstname.lastname@example.org|
|Principal Investigator: Michaela Liedtke|
|Principal Investigator:||Michaela Liedtke||Stanford University|