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Trials / Completed

CompletedNCT01614197

A Trial of Temsirolimus With Etoposide and Cyclophosphamide in Children With Relapsed Acute Lymphoblastic Leukemia and Non-Hodgkins Lymphoma

A Phase I Trial of Temsirolimus (CCI-779, Pfizer, Inc.) in Combination With Etoposide and Cyclophosphamide in Children With Relapsed Acute Lymphoblastic Leukemia and Non-Hodgkins Lymphoma

Status
Completed
Phase
Phase 1
Study type
Interventional
Enrollment
16 (actual)
Sponsor
Therapeutic Advances in Childhood Leukemia Consortium · Academic / Other
Sex
All
Age
1 Year – 21 Years
Healthy volunteers
Not accepted

Summary

This is a phase I study of temsirolimus (Torisel) combined with dexamethasone, cyclophosphamide and etoposide in patients with relapsed acute lymphoblastic leukemia (ALL), lymphoblastic lymphoma (LL) or peripheral T-cell lymphoma (PTL).

Detailed description

Studies have shown that mTOR inhibitors (MTI) inhibit growth of pre-B and T-cell ALL cell lines in vitro and in ALL xenograft models. The MTI temsirolimus was chosen for use in this study due to its weekly intravenous dosing, its more predictable blood levels, and availability of a single-agent pediatric MTD and its sustained biologic effect due to conversion to sirolimus. This study will determine the maximum tolerated dose of temsirolimus that can given in combination with dexamethasone, cyclophosphamide and etoposide in relapsed ALL, LL or PTL. A standard 3-patient cohort dose-escalation design will be used. Response to treatment will be evaluated. Biology tests will be done to evaluate minimal residual disease (MRD), temsirolimus' effect on glucocorticoid resistance, and mTOR inhibition.

Conditions

Interventions

TypeNameDescription
DRUGTemsirolimusDose will be assigned at study entry. Give IV over 30 minutes on days 1 and 8.
DRUGEtoposide100 mg/m2 IV over 1-2 hours daily x 5 on Days 1-5.
DRUGCyclophosphamide440 mg/m2 IV daily x 5 on Days 1-5 given over 30-60 minutes.
DRUGMethotrexatePATIENTS WITH CNS 1 COURSES 2, 4, 6, 8: Give intrathecally to patients who were CNS1 at study entry day 1 of each course at the doses listed below. * Age 1 - 1.99 give 8 mg of methotrexate * Age 2 - 2.99 give10 mg of methotrexate * Age 3 - 8.99 give 12 mg of methotrexate * Age ≥ 9 give 15 mg of methotrexate PATIENTS WITH CNS 2 or 3 DISEASE -COURSE 1: Give intrathecally to patients with CNS 2 or 3 disease at the doses defined by age below on day 6 and then weekly until the patient is CNS 1. COURSES 2-8: Give intrathecally to patients who were CNS 3 at study entry on day 1 of each course. * 8 mg for patients age 1-1.99 * 10 mg for patients age 2-2.99 * 12 mg for patients 3-8.99 years of age * 15 mg for patients \>9 years of age
DRUGHydrocortisoneGiven with Methotrexate and Cytarabine for patients with CNS 2 or 3 disease. COURSE 1: Give intrathecally to patients with CNS 2 or 3 disease at the doses defined by age below on day 6 and then weekly until the patient is CNS 1. COURSES 2-8: Give intrathecally to patients who were CNS 3 at study entry on day 1 of each course. * 8 mg for patients age 1-1.99 * 10 mg for patients age 2-2.99 * 12 mg for patients 3-8.99 years of age * 15 mg for patients \>9 years of age
DRUGCytarabineFor Patients who are CNS1 COURSE 1: Give intrathecally to patients with CNS1 disease at the dose defined by age below on day 1 of course 1 if no other IT was given within 1 week of day 1 of course 1 * Age 1 - 1.99 give 30 mg of Cytarabine * Age 2 - 2.99 give 50mg of Cytarabine * Age ≥ 3 give 70 mg of Cytabine For Patients with CNS 2 or 3 Disease COURSE 1: Give intrathecally to patients with CNS 2 or 3 disease at the doses defined by age below on day 1 if no other IT chemotherapy given within 1 week of day 1 of course 1. Then give weekly until the patient is CNS 1 or 2 (investigator discretion). No more than 5 weekly doses to be given in cycle 1. COURSES 2-8: Give intrathecally to patients who were CNS 2or 3 at study entry on day 1 of each course. * 16 mg for patients age 1-1.99 * 20 mg for patients age 2-2.99 * 24 mg for patients 3-8.99 years of age * 30 mg for patients \>9 years of age

Timeline

Start date
2015-07-03
Primary completion
2019-12-15
Completion
2020-09-04
First posted
2012-06-07
Last updated
2023-07-27
Results posted
2023-07-27

Locations

32 sites across 3 countries: United States, Australia, Canada

Regulatory

Source: ClinicalTrials.gov record NCT01614197. Inclusion in this directory is not an endorsement.