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

NCT02343718

Last updated date
Study Location
Children's and Women's Health Centre of BC Branch
Vancouver, British Columbia, V6H 3V4, Canada
Contact
1-800-718-1021

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Recurrent Lymphoma, Refractory Lymphoma, Solid Tumours, Central Nervous System
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
1-18 year
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- 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:

- At least 90 days have elapsed from total body irradiation, craniospinal radiotherapy or if ≥ 50% radiation of pelvis.

- At least 6 weeks have elapsed from other substantial bone marrow irradiation.

- At least 2 weeks have elapsed from local palliative radiotherapy (small port),

- At least 8 weeks have elapsed from 131I-MIBG therapy for neuroblastoma.

Chemotherapy:

Prior myelosuppressive chemotherapy is permitted provided that it has been at least 3 weeks (6 weeks if nitrosurea) from last administration.

Prior therapy with vinblastine, mTOR inhibitors (such as temsirolimus or sirolimus) is permitted provided patients did not develop progressive disease during treatment and patients have never had to discontinue treatment due to severe adverse events such as interstitial lung disease. At least 3 weeks must have elapsed from the last administration of these agents and registration.

Other Therapy:

Patients may have received other therapies provided that an adequate time has elapsed from completion of therapy/last dose as follows:

- At least 60 days from stem cell transplant/rescue without total body irradiation and no signs of graft-versus-host disease (GVHD).

- At least 7 days (2 weeks for peg-filgrastim) from completion of therapy with hematopoietic growth factors.

- At least 3 half-lives from last administration of monoclonal antibodies.

- At least 6 weeks from any other immunotherapy (e.g. vaccines).

- For biologic anti-neoplastic agents, the longer of the following must have elapsed from last administration prior to study entry: At least 2 weeks or, Standard cycle length of prior regimen or, 5 half-lives.

- Adequate Bone Marrow Function, defined as:

- Absolute neutrophil count (ANC) ≥ 1.0x10^9/L.

- Platelets ≥ 100 x 10^9/L (transfusion independent defined as not receiving platelet transfusions within 7 days prior to registration).

- Hemoglobin > 80 g/L (may receive RBC transfusions). Patients with known bone marrow disease will be eligible for the study provided they meet bone marrow criteria above and they are not known to be refractory to red cell or platelet transfusions.

- Adequate Renal Function, defined as:

- Measured creatinine clearance/GFR ≥ 70 mL/min/1.73 m2 OR,

- Serum creatinine ≤ 1.5 x ULN for age.

- Adequate Liver Function, defined as:

- Total bilirubin ≤ 1.5 x upper limit normal for age.

- ALT ≤ 1.5 x upper limit of normal.

- Serum albumin ≥ 20 g/L.

- Adequate Metabolic Function, defined as:

- Serum triglyceride level ≤ 3.42 mmol/L (300 mg/dL).

- Serum cholesterol level ≤ 7.75 mmol/L (300 mg/dL).

- Blood glucose ≤ ULN for age. Initial sampling may be random; if abnormal, fasting blood glucose must be obtained and be within the upper normal limits for age.

- Adequate Pulmonary Function, defined as:

- No dyspnea at rest.

- O2 saturations of ≥ 92% on room air.

- Patients with any baseline respiratory symptoms, or with a history of pulmonary toxicity, and who are old enough to complete pulmonary function tests, should have documented FEV1 and vital capacity ≥ 50% normal value.

- Electrolytes: ≤ grade 1 (Potassium, Calcium, Magnesium, Phosphate)

- Patient or guardian consent must be obtained on all patients according to local Institutional and/or University Human Experimentation Committee requirements. Children > 8 years old whose parent or guardian has signed consent on their behalf may also sign assent if desired

- Patients must be accessible for treatment and follow up. Patients registered on this trial must be treated and followed at the participating centre

- In accordance with NCIC CTG policy, protocol treatment is to begin within 5 working days of patient registration

Exclusion Criteria
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- 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:


1. Active or uncontrolled infections;


2. Uncontrolled diabetes;


3. Any other medical conditions that might be aggravated by treatment;


4. History of an underlying inherited or ongoing bleeding disorder;


5. 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.


- Patients receiving strong/potent CYP3A4/5 substrates/inhibitors/inducers. These
agents must have been discontinued for at least 14 days prior to registration.
Grapefruit juice is also not permitted for at least 14 days prior to registration
and at any time during study participation.


- Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of
reproductive potential may not participate unless they have agreed to use a highly
effective contraceptive method. Pregnant or breast feeding females will not be entered
on this study due to the potential fetal and teratogenic adverse events.


- Patients who in the opinion of the investigator may not be able to comply with the
safety monitoring requirements of the study.

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Recurrent Lymphoma, Refractory Lymphoma, Solid Tumours, Central Nervous SystemVinblastine and Temsirolimus in Pediatrics With Recurrent or Refractory Lymphoma or Solid Tumours Including CNS Tumours
NCT02343718
  1. Vancouver, British Columbia
  2. Halifax, Nova Scotia
  3. Hamilton, Ontario
  4. Ottawa, Ontario
  5. Toronto, Ontario
  6. Montreal, Quebec
ALL GENDERS
1 Year+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE Vinblastine and Temsirolimus in Pediatrics With Recurrent or Refractory Lymphoma or Solid Tumours Including CNS Tumours
Official Title  ICMJE A Study of Vinblastine and Temsirolimus in Pediatric Patients With Recurrent or Refractory Lymphoma or Solid Tumours Including CNS Tumours
Brief Summary The purpose of this study is to determine the best dose of vinblastine that can be given with a new drug, temsirolimus.
Detailed Description Vinblastine is already approved in the treatment of some types of cancer in children and temsirolimus is already used to treat some adult cancers in Canada. Temsirolimus has been shown to slow the growth of tumours in animals but it is not known if it can also slow tumour growth in children. Laboratory studies suggest that giving both vinblastine and temsirolimus may offer better results than giving vinblastine alone.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Recurrent Lymphoma
  • Refractory Lymphoma
  • Solid Tumours
  • Central Nervous System
Intervention  ICMJE
  • Drug: Vinblastine
  • Drug: Temsirolimus
Study Arms  ICMJE Experimental: Vinblastine and Temsirolimus

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.

Interventions:
  • Drug: Vinblastine
  • Drug: Temsirolimus
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 31, 2017)
7
Original Estimated Enrollment  ICMJE
 (submitted: January 21, 2015)
18
Actual Study Completion Date  ICMJE January 16, 2019
Actual Primary Completion Date September 28, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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:

  • At least 90 days have elapsed from total body irradiation, craniospinal radiotherapy or if ? 50% radiation of pelvis.
  • At least 6 weeks have elapsed from other substantial bone marrow irradiation.
  • At least 2 weeks have elapsed from local palliative radiotherapy (small port),
  • At least 8 weeks have elapsed from 131I-MIBG therapy for neuroblastoma.

Chemotherapy:

Prior myelosuppressive chemotherapy is permitted provided that it has been at least 3 weeks (6 weeks if nitrosurea) from last administration.

Prior therapy with vinblastine, mTOR inhibitors (such as temsirolimus or sirolimus) is permitted provided patients did not develop progressive disease during treatment and patients have never had to discontinue treatment due to severe adverse events such as interstitial lung disease. At least 3 weeks must have elapsed from the last administration of these agents and registration.

Other Therapy:

Patients may have received other therapies provided that an adequate time has elapsed from completion of therapy/last dose as follows:

  • At least 60 days from stem cell transplant/rescue without total body irradiation and no signs of graft-versus-host disease (GVHD).
  • At least 7 days (2 weeks for peg-filgrastim) from completion of therapy with hematopoietic growth factors.
  • At least 3 half-lives from last administration of monoclonal antibodies.
  • At least 6 weeks from any other immunotherapy (e.g. vaccines).
  • For biologic anti-neoplastic agents, the longer of the following must have elapsed from last administration prior to study entry: At least 2 weeks or, Standard cycle length of prior regimen or, 5 half-lives.

    - Adequate Bone Marrow Function, defined as:

  • Absolute neutrophil count (ANC) ? 1.0x10^9/L.
  • Platelets ? 100 x 10^9/L (transfusion independent defined as not receiving platelet transfusions within 7 days prior to registration).
  • Hemoglobin > 80 g/L (may receive RBC transfusions). Patients with known bone marrow disease will be eligible for the study provided they meet bone marrow criteria above and they are not known to be refractory to red cell or platelet transfusions.

    - Adequate Renal Function, defined as:

  • Measured creatinine clearance/GFR ? 70 mL/min/1.73 m2 OR,
  • Serum creatinine ? 1.5 x ULN for age.

    - Adequate Liver Function, defined as:

  • Total bilirubin ? 1.5 x upper limit normal for age.
  • ALT ? 1.5 x upper limit of normal.
  • Serum albumin ? 20 g/L.

    - Adequate Metabolic Function, defined as:

  • Serum triglyceride level ? 3.42 mmol/L (300 mg/dL).
  • Serum cholesterol level ? 7.75 mmol/L (300 mg/dL).
  • Blood glucose ? ULN for age. Initial sampling may be random; if abnormal, fasting blood glucose must be obtained and be within the upper normal limits for age.
  • Adequate Pulmonary Function, defined as:

    • No dyspnea at rest.
    • O2 saturations of ? 92% on room air.
    • Patients with any baseline respiratory symptoms, or with a history of pulmonary toxicity, and who are old enough to complete pulmonary function tests, should have documented FEV1 and vital capacity ? 50% normal value.
  • Electrolytes: ? grade 1 (Potassium, Calcium, Magnesium, Phosphate)
  • Patient or guardian consent must be obtained on all patients according to local Institutional and/or University Human Experimentation Committee requirements. Children > 8 years old whose parent or guardian has signed consent on their behalf may also sign assent if desired
  • Patients must be accessible for treatment and follow up. Patients registered on this trial must be treated and followed at the participating centre
  • In accordance with NCIC CTG policy, protocol treatment is to begin within 5 working days of patient registration

Exclusion Criteria:

  • 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:

    1. Active or uncontrolled infections;
    2. Uncontrolled diabetes;
    3. Any other medical conditions that might be aggravated by treatment;
    4. History of an underlying inherited or ongoing bleeding disorder;
    5. 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.
    • Patients receiving strong/potent CYP3A4/5 substrates/inhibitors/inducers. These agents must have been discontinued for at least 14 days prior to registration. Grapefruit juice is also not permitted for at least 14 days prior to registration and at any time during study participation.
  • Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use a highly effective contraceptive method. Pregnant or breast feeding females will not be entered on this study due to the potential fetal and teratogenic adverse events.
  • Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study.
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 1 Year to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02343718
Other Study ID Numbers  ICMJE I218
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD:No
Responsible Party Canadian Cancer Trials Group
Study Sponsor  ICMJE Canadian Cancer Trials Group
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Study Chair:Sylvain BaruchelHospital for Sick Children, Toronto ON Canada
Study Chair:Rebecca DeyellChildren's & Women's Health Centre of BC Branch, Vancouver BC, Canada
PRS Account Canadian Cancer Trials Group
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP