Bortezomib and Combination Chemotherapy in Treating Young Patients With Relapsed Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma
This phase II trial is studying 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.
- Bortezomib concentrations 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 CTCAE v4.0 [ 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.
|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)
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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
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 IV or orally
Other Names:Other: laboratory biomarker analysis
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I. To estimate the toxicity, second complete response (CR2) rate at the end of Block 1 therapy, and 4-month event-free survival (EFS) for pediatric and young adult patients with relapsed acute lymphoblastic leukemia (ALL) treated with bortezomib in combination with intensive re-Induction chemotherapy.
II. To evaluate bortezomib pharmacokinetics (PK) in patients receiving the combination regimen.
I. To assess minimal residual disease (MRD) in bone marrow following completion of each therapy block.
II. To assess the feasibility of measuring leukemia initiating cells (LIC) in patient samples before and after chemotherapy.
III. To discover biologic pathways associated with response and drug resistance using gene and protein expression profiles at baseline and following initial exposure to chemotherapy.
IV. To determine if bortezomib inhibits lymphoblast NF-kappa-B activity in leukemia patients.
REINDUCTION BLOCK 1: Patients receive cytarabine intrathecally (IT) on day 1; vincristine sulfate IV on days 1, 8, 15, and 22; doxorubicin hydrochloride IV over 15 minutes on day 1; oral prednisone twice daily on days 1-29; bortezomib IV on days 1, 4, 8, and 11; and pegaspargase intramuscularly (IM) on days 2, 8, 15, and 22. Patients with central nervous system (CNS)-negative disease (CNS1 or CNS2) also receive methotrexate IT on days 15 and 29; patients with CNS-positive disease (CNS3) receive triple intrathecal therapy (TIT) comprising methotrexate, hydrocortisone, and cytarabine IT on days 8, 15, 22, and 29. After completion of reinduction block 1, patients with ALL and M2 or M3 bone marrow proceed directly to reinduction block 2. Patients with ALL and M1 bone marrow or lymphoblastic lymphoma proceed to reinduction block 2 after blood counts recover. Patients with persistent cerebral spinal fluid (CSF) blasts after 6 doses of TIT or patients with progressive lymphoblastic lymphoma are removed from the study.
REINDUCTION BLOCK 2: Patients receive etoposide phosphate IV over 1-2 hours on days 1-5; cyclophosphamide IV over 1 hour on days 1-5; bortezomib IV on days 1, 4, and 8; filgrastim (G-CSF) subcutaneously (SC) or IV daily beginning on day 6 and continuing until blood counts recover*; high-dose methotrexate IV on day 22; and leucovorin calcium orally or IV every 6 hours on days 23 and 24. Patients with CNS-negative disease also receive methotrexate IT on days 1 and 22; patients with CNS-positive disease receive TIT on days 1 and 22. After completion of reinduction block 2, patients proceed to reinduction block 3 immediately or when blood counts recover. Patients with disease progression are removed from the study.
NOTE: *Patients do not receive G-CSF on day 8.
REINDUCTION BLOCK 3: Patients receive cytarabine IV over 3 hours twice daily on days 1, 2, 8, and 9; L-asparaginase IM on days 2 and 9; and G-CSF SC or IV daily beginning on day 10 and continuing until blood counts recover.
After completion of study treatment, patients are followed every 6 months for 3 years and then annually for 2 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00873093
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|Principal Investigator:||Terzah Horton||Children's Oncology Group|