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
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGDexamethasone
Given PO or IV
OTHERLaboratory Biomarker Analysis
Correlative studies
DRUGMethotrexate
Given IT
DRUGMitoxantrone Hydrochloride
Given IV
DRUGPegaspargase
Given IV
OTHERPharmacological Study
Correlative studies
DRUGTemsirolimus
Given IV
DRUGVincristine Sulfate
Given IV
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis: * Patients must have second (2nd) or greater relapse of pre-B ALL, T-cell ALL, lymphoblastic lymphoma, or peripheral T-cell lymphoma; patients may not have refractory disease * Patients with leukemia must have had histologic verification of the malignancy at the most recent relapse, including immunophenotyping to confirm diagnosis * Disease Status: * Leukemia: patients with leukemia must have an M3 marrow with or without extramedullary site of relapse OR an M2 bone marrow with an extramedullary site of relapse; patients with central nervous system (CNS) 3 status are not eligible for enrollment * Lymphoma: patients with non-Hodgkin lymphoma must have either measurable or evaluable disease * Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life * Karnofsky \>= 50% for patients \> 16 years of age and Lansky \>= 50 for patients =\< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score * Prior Therapy: * Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy, defined as resolution of all such toxicities to =\< grade 2 or per the inclusion/
Exclusion criteria
* Myelosuppressive chemotherapy: * Patients with leukemia or lymphoma who relapse while receiving standard maintenance chemotherapy with steroid, vincristine pulses and oral outpatient chemotherapy will not be required to have a waiting period before enrollment onto this study * Patients who relapse while they are not receiving standard maintenance therapy, must have fully recovered from all acute toxic effects of prior therapy; at least 14 days must have elapsed after the completion of cytotoxic therapy, with the exception of hydroxyurea * Note: cytoreduction with hydroxyurea in patients can be initiated and continued for up to 24 hours prior to the start of protocol therapy * Hematopoietic growth factors: at least 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair * Biologic (anti-neoplastic agent): at least 7 days after the last dose of a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair * Immunotherapy: at least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines * Monoclonal antibodies: at least 3 half-lives of the antibody after the last dose of a monoclonal antibody with the exception of blinatumomab; patients must have been off blinatumomab infusion for at least 7 days and all drug-related toxicity must have resolved to grade 1 or lower as outline in the inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-limiting toxicity of temsirolimus in combination with intensive re-induction chemotherapy graded according to the NCI CTCAE v4.0 | 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 | Up to day 36 | A descriptive summary of all toxicities will be reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CR rate according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria | Up to 30 days post-treatment | — |
| MRD levels present at the end of induction | 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 | 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). |
Countries
Canada, United States
Outcome results
None listed