Temsirolimus, Dexamethasone, Mitoxantrone Hydrochloride, Vincristine Sulfate, and Pegaspargase in Treating Young Patients With Relapsed Acute Lymphoblastic Leukemia or Non-Hodgkin Lymphoma
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|ClinicalTrials.gov Identifier: NCT01403415|
Recruitment Status : Completed
First Posted : July 27, 2011
Last Update Posted : July 10, 2015
|Condition or disease||Intervention/treatment||Phase|
|Childhood B Acute Lymphoblastic Leukemia Childhood T Acute Lymphoblastic Leukemia Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma Recurrent Childhood Acute Lymphoblastic Leukemia Recurrent Childhood Lymphoblastic Lymphoma||Drug: Dexamethasone Other: Laboratory Biomarker Analysis Drug: Methotrexate Drug: Mitoxantrone Hydrochloride Drug: Pegaspargase Other: Pharmacological Study Drug: Temsirolimus Drug: Vincristine Sulfate||Phase 1|
I. To estimate the maximum-tolerated dose (MTD) and/or recommended phase 2 dose of temsirolimus administered weekly for 2 doses in combination with intensive re-induction chemotherapy in children with relapsed acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL).
II. To define and describe the toxicities of temsirolimus in combination with intensive re-induction chemotherapy in children with relapsed ALL or NHL administered on this schedule.
I. To compare minimal-residual disease (MRD) levels present at end of induction to historical control in patients with relapsed ALL or NHL with bone marrow involvement of disease.
II. To determine the complete remission (CR) rate in patients with ALL or NHL who receive this regimen.
III. To evaluate responsiveness of patient ALL cells to mammalian target of rapamycin (mTOR) inhibition using in vitro and in vivo pharmacodynamic assessment of the response of ALL blasts to temsirolimus.
OUTLINE: This is a dose-escalation study of temsirolimus.
Patients receive dexamethasone orally (PO) or intravenously (IV) on days 1-5 and 15-19; mitoxantrone hydrochloride IV over 30 minutes on days 1-2; temsirolimus IV over 30 minutes on days 1 and 8; vincristine sulfate IV on days 1, 8, 15, and 22; and pegaspargase IV over 1 hour on days 3 and 17. Some patients may also receive methotrexate intrathecally (IT) up to 72 hours prior to or on day 1 and on day 8.
After completion of study therapy, patients are followed up for 30 days.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||13 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 Study of Temsirolimus in Combination With Intensive Re-induction Therapy for Children With Relapsed Acute Lymphoblastic Leukemia and Non-Hodgkin Lymphoma|
|Study Start Date :||September 2011|
|Actual Primary Completion Date :||May 2015|
Experimental: Treatment (temsirolimus, combination chemotherapy)
Patients receive dexamethasone PO or IV on days 1-5 and 15-19; mitoxantrone hydrochloride IV over 30 minutes on days 1-2; temsirolimus IV over 30 minutes on days 1 and 8; vincristine sulfate IV on days 1, 8, 15, and 22; and pegaspargase IV over 1 hour on days 3 and 17. Some patients may also receive methotrexate IT up to 72 hours prior to or on day 1 and on day 8.
Given PO or IV
Other: Laboratory Biomarker Analysis
Drug: Mitoxantrone Hydrochloride
Other: Pharmacological Study
Drug: Vincristine Sulfate
- Dose-limiting toxicity of temsirolimus in combination with intensive re-induction chemotherapy graded according to the NCI CTCAE v4.0 [ Time Frame: Up to 30 days post-treatment ]A descriptive summary of all toxicities will be reported.
- MTD and/or recommended phase II dose defined as the maximum dose at which fewer than one-third of patients experience dose-limiting toxicity graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 [ Time Frame: Up to day 36 ]A descriptive summary of all toxicities will be reported.
- CR rate according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria [ Time Frame: Up to 30 days post-treatment ]
- MRD levels present at the end of induction [ Time Frame: Up to 30 days post-treatment ]Compared to a historical control in patients with bone marrow involvement of disease using a t-test or nonparametric analog.
- mTOR inhibitor effects on downstream signaling in patient lymphoblasts In vitro and in vivo [ Time Frame: Up to 30 days post-treatment ]The pharmacodynamic data will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01403415
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|Principal Investigator:||Susan Rheingold||COG Phase I Consortium|