Vinblastine and Temsirolimus in Pediatrics With Recurrent or Refractory Lymphoma or Solid Tumours Including CNS Tumours

NCT02343718 | Completed Phase 1 DMC

• 1 other identifier: I218
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 6

Brief Summary

The purpose of this study is to determine the best dose of vinblastine that can be given with a new drug, temsirolimus.

Conditions

Recurrent Lymphoma; Refractory Lymphoma; Solid Tumours; Central Nervous System

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Adverse Events as a Measure of Safety and Tolerability

  To determine the recommended phase II dose (RP2D) of the combination of vinblastine and temsirolimus (administered as a weekly intravenous dose) in children with recurrent or refractory solid tumours including central nervous system (CNS) tumours and lymphoma and to describe the associated toxicities in children

  4 years

Study Arms (1)

Vinblastine and Temsirolimus

EXPERIMENTAL

Vinblastine starting dose: Weight \>12 kg 4mg/m\^2 Weight ≤ 12 kg 0.13mg/kg IV push for 1 minute Days 1, 8, 15, 22, 29 and 36. Cycle length is 6 weeks up to 6 cycles. Temsirolimus starting dose: Weight \>12 kg 15mg/m\^2 Weight ≤ 12 kg 0.5 mg/kg IV for 1 hour on days 1, 8, 15, 22, 29 and 36. Cycle length is 6 weeks up to 6 cycles.

Drug: Vinblastine; Drug: Temsirolimus

Interventions

Vinblastine DRUG

Vinblastine and Temsirolimus

Temsirolimus DRUG

Vinblastine and Temsirolimus

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients must have histological verification of malignancy at initial diagnosis or at relapse.
• Note: Histological verification is not required for patients with optic pathway gliomas, or patients with pineal tumours and elevations of CSF or serum tumour markers
• Solid tumours (excluding soft tissue sarcomas), CNS and localized brainstem tumours (excluding diffuse intrinsic pontine gliomas (DIPG)) or,
• Lymphomas including Hodgkin's disease, non-Hodgkin's lymphoma and post-transplant lymphoproliferative disease (PTLD)
• Patients must have relapsed or refractory disease for which there is no known curative therapy, with either measurable or evaluable disease
• Age ≥ 1 year and ≤ 18 years at time of registration
• Performance status:
• Patients ≤ 16 years: Lansky ≥ 50%
• Patients ≥ 16 years: Karnofsky \> 50%
• Prior Therapy
• Patients must have received at least one prior regimen prior to registration. There is no limit to the number of prior regimens. Patients must have recovered from the acute effects and reversible toxicities related to prior therapy and have adequate washout prior to study entry as follows:
• Surgery:
• Previous major surgery is permitted provided that it has been at least 28 days prior to registration and wound healing has occurred. Additionally, at least 7 days must have elapsed since last biopsy or other minor surgery and wound healing must have occurred.
• Radiation:
• Prior radiotherapy is permitted provided that from last dose to registration:

You may not qualify if:

• Patients with serious illness or medical condition that would not permit the patient to be managed according to the protocol including, but not limited to:
• Active or uncontrolled infections;
• Uncontrolled diabetes;
• Any other medical conditions that might be aggravated by treatment;
• History of an underlying inherited or ongoing bleeding disorder;
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events (e.g. heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age) or mean resting corrected QT interval (QTc) \> 470 msec).
• Patients with a history of allergic reactions or known hypersensitivity to the study drug(s) or their components, or compounds of similar chemical or biologic composition.
• Patients with lymphoma or solid tumours (except primary CNS tumours) who have untreated brain metastases, untreated spinal cord compression or meningeal metastases are not eligible (CNS imaging is not required to rule this out unless there is a clinical suspicion of CNS disease). Patients with treated brain metastases who have radiologic evidence of stable brain metastases, with no evidence of cavitation or hemorrhage in the brain lesion, are eligible providing that they are asymptomatic. If being treated with corticosteroids, must be at a stable or decreasing dose for at least 7 days prior to study entry.
• Concurrent Medications
• Patients receiving other investigational agents.
• Patients receiving other anti-cancer agents, or radiation therapy.
• Patients receiving angiotensin-converting enzyme (ACE) inhibitors.
• Patients receiving QT/QTc-prolonging drugs.
• Patients receiving anticoagulants.
• Patients receiving anti-GVHD or agents to prevent organ rejection post-transplant.

Sponsors & Collaborators

• Canadian Cancer Trials Group: lead
• Pfizer: collaborator

Study Sites (6)

Children's and Women's Health Centre of BC Branch

Vancouver, British Columbia, V6H 3V4, Canada

Location

Izaak Walton Killam (IWK) Health Centre

Halifax, Nova Scotia, B3K 6R8, Canada

Location

McMaster Children's Hospital

Hamilton, Ontario, L8N 3Z5, Canada

Location

Children's Hospital of Eastern Ontario

Ottawa, Ontario, K1H 8L1, Canada

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

CHU Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Related Publications (1)

• Deyell RJ, Wu B, Rassekh SR, Tu D, Samson Y, Fleming A, Bouffet E, Sun X, Powers J, Seymour L, Baruchel S, Morgenstern DA. Phase I study of vinblastine and temsirolimus in pediatric patients with recurrent or refractory solid tumors: Canadian Cancer Trials Group Study IND.218. Pediatr Blood Cancer. 2019 Mar;66(3):e27540. doi: 10.1002/pbc.27540. Epub 2018 Nov 4.

  PMID: 30393943 RESULT

MeSH Terms

Conditions

Lymphoma

Interventions

Vinblastine; temsirolimus

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Sylvain Baruchel

  Hospital for Sick Children, Toronto ON Canada

  STUDY CHAIR

• Rebecca Deyell

  Children's & Women's Health Centre of BC Branch, Vancouver BC, Canada

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2015
• First Posted: January 22, 2015
• Study Start: June 24, 2015
• Primary Completion: September 28, 2017
• Study Completion: January 16, 2019
• Last Updated: August 4, 2023

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (6)