NCT01403415

Temsirolimus, Dexamethasone, Mitoxantrone Hydrochloride, Vincristine Sulfate, and Pegaspargase in Treating Young Patients With Relapsed Acute Lymphoblastic Leukemia or Non-Hodgkin Lymphoma

A Phase 1 Study of Temsirolimus in Combination With Intensive Re-induction Therapy for Children With Relapsed Acute Lymphoblastic Leukemia and Non-Hodgkin Lymphoma

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 13 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 1 Year – 21 Years
• Healthy volunteers: Not accepted

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.

Conditions

• 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

Interventions

Type	Name	Description
DRUG	Dexamethasone	Given PO or IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Methotrexate	Given IT
DRUG	Mitoxantrone Hydrochloride	Given IV
DRUG	Pegaspargase	Given IV
OTHER	Pharmacological Study	Correlative studies
DRUG	Temsirolimus	Given IV
DRUG	Vincristine Sulfate	Given IV

Timeline

• Start date: 2011-09-01
• Primary completion: 2015-05-01
• First posted: 2011-07-27
• Last updated: 2015-07-10

Locations

31 sites across 2 countries: United States, Canada