Bortezomib and Combination Chemotherapy in Treating Young Patients With Relapsed Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma
This pilot, phase II trial studies the side effects of giving bortezomib together with combination chemotherapy and to see how well it works in treating young patients with relapsed acute lymphoblastic leukemia or lymphoblastic lymphoma. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with combination chemotherapy may kill more cancer cells.
B-cell Adult Acute Lymphoblastic Leukemia
B-cell Childhood Acute Lymphoblastic Leukemia
Recurrent Adult Acute Lymphoblastic Leukemia
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Childhood Acute Lymphoblastic Leukemia
Recurrent Childhood Lymphoblastic Lymphoma
T-cell Adult Acute Lymphoblastic Leukemia
T-cell Childhood Acute Lymphoblastic Leukemia
Drug: doxorubicin hydrochloride
Drug: therapeutic hydrocortisone
Drug: liposomal vincristine sulfate
Drug: etoposide phosphate
Drug: leucovorin calcium
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Pilot Trial of Bortezomib (PS-341, Velcade) in Combination With Intensive Re-Induction Therapy for Children With Relapsed Acute Lymphoblastic Leukemia (ALL) and Lymphoblastic Lymphoma (LL)|
- Second complete remission rate at the end of block 1 reinduction chemotherapy [ Time Frame: 29 days ] [ Designated as safety issue: No ]Descriptive statistics will be used to assess CR2 rates by stratum including calculation of 95% confidence intervals.
- PK of bortezomib in patients receiving multi-agent combination therapy [ Time Frame: Day 8 of blocks 1 and 2 ] [ Designated as safety issue: No ]
- Toxicity according to NCI Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
- Minimal residual disease [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]A one-sample Z-test of proportions (one-sided, alpha= 5%) will be used.
- NF-kB activity [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]NF-kB activity will be measured as a continuous variable (ng NF-kB/ug protein). Differences in NF-kB activity between time points will be assessed using summary statistics such as mean, standard deviation, and range.
- Expression of apoptotic and cell cycle proteins assessed by using gene and tissue microarrays and immunoblots [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]Characterized using descriptive statistics. If differences are noted between pre- and post-treatment protein expression, pairwise comparisons will be made using paired t-test or an equivalent nonparametric test. The normality assumption will be assessed on the log-transformed data prior to paired t-test evaluation.
- Change in stem cell percentage [ Time Frame: Baseline to post-treatment with bortezomib ] [ Designated as safety issue: No ]Will use descriptive statistics to assess mean +/- standard deviation for stem cell percentage before and after bortezomib treatment. If there appears to be a difference in responders vs. non-responders, stem cell percentage differences between responders and non-responders will be compared using a paired t-test or equivalent nonparametric test.
- Plasma concentration-time profiles [ Time Frame: Up to day 8 of block 2 ] [ Designated as safety issue: No ]Will be analyzed using descriptive statistics and will be graphically displayed by age group and stratum. PK data will be analyzed using methods such as nonlinear mixed effects modeling to estimate bortezomib clearance and volume of distribution (and the associated 95% confidence intervals) in each age group (2-11 years and 12-16 years of age).
|Study Start Date:||March 2009|
|Estimated Primary Completion Date:||September 2014 (Final data collection date for primary outcome measure)|
Experimental: Treatment (bortezomib and combination chemotherapy)
See Detailed Description
Other Names:Drug: doxorubicin hydrochloride
Other Names:Drug: therapeutic hydrocortisone
Other Names:Drug: liposomal vincristine sulfate
Other Names:Drug: cytarabine
Given IT or IV
Other Names:Drug: prednisone
Given PO or IV
Other Names:Drug: bortezomib
Other Names:Drug: pegaspargase
Other Names:Drug: methotrexate
Given IT or IV
Other Names:Drug: etoposide phosphate
Other Names:Drug: cyclophosphamide
Other Names:Biological: filgrastim
Given IV or SC
Other Names:Drug: leucovorin calcium
Given PO or IV
Other Names:Other: laboratory biomarker analysis
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00873093
Show 171 Study Locations
|Principal Investigator:||Terzah Horton||Children's Oncology Group|