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

Titre officiel

A Phase 1 Study of Temsirolimus (CCI-779, IND# 61010) in Combination With Intensive Re-Induction Therapy for Children With Relapsed Acute Lymphoblastic Leukemia and Non-Hodgkin Lymphoma

Sommaire:

JUSTIFICATION : Le temsirolimus pourrait stopper la multiplication des cellules cancéreuses en inhibant certaines des enzymes indispensables à la croissance cellulaire. Les médicaments utilisés pour la chimiothérapie, comme le dexaméthasone, le chlorhydrate de mitoxantrone, le sulfate de vincristine et la pegaspargase, agissent de différentes façons pour stopper la multiplication des cellules cancéreuses, soit en les tuant soit en les empêchant de se diviser. L'administration de temsirolimus avec une chimiothérapie d'association pourrait permettre de tuer un plus grand nombre de cellules cancéreuses. BUT : Cet essai de phase I a pour but de déterminer les effets secondaires du temsirolimus et la meilleure dose de cet agent à donner en concomitance avec le dexaméthasone, le chlorhydrate de mitoxantrone, le sulfate de vincristine et la pegaspargase pour traiter de jeunes patients atteints d’une leucémie aiguë lymphoblastique ou d’un lymphome non hodgkinien en récidive.

Description de l'essai

Primary Outcome:

• MTD and/or recommended phase II dose of temsirolimus in combination with intensive re-induction chemotherapy, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0
• Dose-limiting toxicity of temsirolimus in combination with intensive re-induction chemotherapy graded according to the NCI CTCAE v4.0

Secondary Outcome:

• Comparison between MRD levels present at the end of induction with historical control in patients with bone marrow involvement of disease
• CR rate according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria
• In vitro and in vivo pharmacodynamics of temsirolimus

PRIMARY OBJECTIVES:
I. To estimate the maximum-tolerated dose (MTD) and/or recommended phase 2 dose of temsirolimus administered weekly for 3 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 mTOR inhibition using in vitro and in vivo pharmacodynamic assessment of the response of ALL blasts to temsirolimus. OUTLINE:

This is a multicentre, dose-escalation study of temsirolimus. Patients receive dexamethasone orally (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 intrathecally (IT) up to 72 hours prior to or on day 1 and on day 8. Patients undergo blood and bone marrow collection at baseline, during, and after completion of study for in vitro and in vivo pharmacodynamic studies. After completion of study therapy, patients are followed up for 30 days.

Voir cet essai sur ClinicalTrials.gov