This phase I trial studies the side effects and the best dose of temsirolimus when given together with dexamethasone, mitoxantrone hydrochloride, vincristine sulfate, and pegaspargase in treating young patients with relapsed acute lymphoblastic leukemia or non-Hodgkin lymphoma. Temsirolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as dexamethasone, mitoxantrone hydrochloride, vincristine sulfate, and pegaspargase work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving temsirolimus with combination chemotherapy may be and effective treatment for acute lymphoblastic leukemia or non-Hodgkin lymphoma.
PRIMARY OBJECTIVES: 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. SECONDARY OBJECTIVES: 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
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
13
Given PO or IV
Correlative studies
Given IT
Given IV
Given IV
Correlative studies
Given IV
Given IV
Children's Hospital of Alabama
Birmingham, Alabama, United States
Phoenix Childrens Hospital
Phoenix, Arizona, United States
Childrens Hospital of Orange County
Orange, California, United States
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, United States
Rady Children's Hospital - San Diego
San Diego, California, United States
Dose-limiting toxicity of temsirolimus in combination with intensive re-induction chemotherapy graded according to the NCI CTCAE v4.0
A descriptive summary of all toxicities will be reported.
Time frame: Up to 30 days post-treatment
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
A descriptive summary of all toxicities will be reported.
Time frame: Up to day 36
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
Compared to a historical control in patients with bone marrow involvement of disease using a t-test or nonparametric analog.
Time frame: Up to 30 days post-treatment
mTOR inhibitor effects on downstream signaling in patient lymphoblasts In vitro and in vivo
The pharmacodynamic data will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).
Time frame: Up to 30 days post-treatment
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UCSF Medical Center-Parnassus
San Francisco, California, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, United States
Riley Hospital for Children
Indianapolis, Indiana, United States
...and 21 more locations