Recurrent Childhood MedulloblastomaPhase 1NCT02271711
Expanded Natural Killer Cell Infusion in Treating Younger Patients With Recurrent/Refractory Brain Tumors
A Phase 1 study testing Laboratory Biomarker Analysis and Natural Killer Cell Therapy in people with Recurrent Childhood Medulloblastoma and Recurrent Ependymoma, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
This phase I trial studies the side effects and best dose of expanded natural killer cells in treating younger patients with brain tumors that have come back or do not respond to treatment. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Recurrent Childhood Medulloblastoma, Recurrent Ependymoma, Recurrent Medulloblastoma
- What is being tested?
- Laboratory Biomarker Analysis and Natural Killer Cell Therapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Mar 2015to 28 Aug 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Diagnosis: patients with recurrent/refractory medulloblastoma (MB), atypical teratoid (AT)/rhabdoid tumors (RT) or ependymoma involving the brain and/or spine at original diagnosis or relapse; they must have histological verification at diagnosis and/or relapse; patient must have presented with these tumors in the posterior fossa (PF) or relapsed in the PF
- Patient must have either measurable or evaluable tumor
- Presence of or determined by neurosurgery to be a candidate for an implanted catheter in the ventricles to receive NK cell infusion
- Life expectancy of at least 12 weeks in opinion of principal investigator (PI) and/or designee
- Lansky score of 50 or greater if =<16 years of age or a Karnofsky score of 50 or greater if > 16 years of age (NOTE: patients who are unable to walk because of paralysis, but who are in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score)
- Neurologic deficits must have been relatively stable for a minimum of 1 week prior to study enrollment
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- Patients must have recovered from the acute toxic effects of all prior anticancer chemotherapy
- Patient must be 4 weeks off any palliative radiation or craniospinal radiation
- Absolute neutrophil count (ANC) of >= 1000/uL
- Platelet count of >= 30,000
- Hemoglobin of >= 9.0 g/dl
- Patients with a seizure disorder may be enrolled if well-controlled and on non-enzyme inducing anticonvulsants
- Patient or patient's legal representative, parent(s), or guardian able to provide written informed consent
Who cannot join
- Enrolled in another treatment protocol
- Evidence of untreated infection
- Extra-cranial metastasis
- Chronic corticosteroid dependence (except replacement therapy)
- Extensive disease, disease location, and/or co-morbid condition that the PI or designee considers unsafe for surgical intervention of NK cell infusion
- Pregnant or lactating women
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I Study of Intraventricular Infusions of Autologous Ex Vivo-Expanded NK Cells in Children With Recurrent/Refractory Malignant Posterior Fossa Tumors of the Central Nervous System. NOAH's (New Opportunity, Advancing Hope) Protocol
This phase I trial studies the side effects and best dose of expanded natural killer cells in treating younger patients with brain tumors that have come back or do not respond to treatment. Infusing a particular type of a patient's own white blood cells called natural killer cells that have been through a procedure to expand (increase) their numbers may work in treating patients with recurrent/refractory brain tumors.
Read the detailed description
PRIMARY OBJECTIVES:
- To establish the safety, feasibility, efficacy, and maximum tolerated dose (MTD) of administering autologous natural killer (NK) cells that have been propagated ex vivo with artificial antigen-presenting cells (aAPC) and administered directly into the ventricle in recurrent /refractory malignant posterior fossa tumors.
SECONDARY OBJECTIVES:
- To assess the antitumor activity based on imaging and cytology of autologous NK cell locoregional administration directly into the lateral or fourth ventricle.
II. To determine the persistence of adoptively-transferred expanded NK cells (as performed with excess NK cells, via optional correlative studies).
III. Determine the immunophenotype and function of expanded NK cells. IV. Determine the overall response of medulloblastoma to NK-cell therapy. V. Correlate NK cell persistence, phenotype, and function with overall response.
OUTLINE: This is a dose-escalation study.
Patients receive autologous expanded NK cells intravenously (IV) into the ventricle over 3 minutes once weekly on weeks 1-3. Treatment repeats every 4 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients experiencing disease progression may continue treatment at the discretion of the treating physician if pseudo-progression or benefit of slowed progression is suspected.
After completion of study treatment, patients are followed up within 30 days.
- Being tested
- Laboratory Biomarker Analysis, Natural Killer Cell Therapy
- Medical subject headings
- Medulloblastoma, Ependymoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Laboratory Biomarker AnalysisOther
Correlative studies
Natural Killer Cell TherapyBiological
Given autologous ex-vivo expanded NK cells IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (autologous ex vivo-expanded NK cells) | Experimental | Patients receive autologous expanded NK cells IV into the ventricle over 3 minutes once weekly on weeks 1-3. Treatment repeats every 4 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients experiencing disease progression may continue treatment at the discretion of the treating physician if pseudo-progression or benefit of slowed progression is suspected. Receives: Other: Laboratory Biomarker Analysis; Biological: Natural Killer Cell Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD) of natural killer (NK) cells
Defined as the highest dose studied in which 6 patients have been treated at most 1 patient with dose limiting toxicities are observed. Toxicities will be summarized by tabulation in terms of type, grade and attribution for each dose level of each group of patients studied at the end of the trial.
Measured: 4 weeks
Secondary outcomes (6)
Activation status of NK cells
Determined by flow-based activation assay determining cluster of differentiation (CD)107a expression of NK cells in response to standardized targets.
Measured: Up to 30 days after the last infusion in course 3
Persistence of NK cells
Peripheral blood and cerebrospinal fluid (CSF) will be obtained before therapy, during the NK cell treatment period, and after NK cell treatment.
Measured: Up to 30 days after the last infusion in course 3
Function of NK cells
Assessed by cell lysis of standardized targets.
Measured: Up to 30 days after the last infusion in course 3
Response of medulloblastoma to NK cells
Antitumor activity will be described for each group of patients based on imaging and cytology. Clinical response will be correlated with NK cell persistence in vivo, cytokine levels, and expression of activation markers.
Measured: Up to 30 days after the last infusion in course 3
Feasibility of NK cell manufacturing
If analysis shows < 50% successful product generation after at least six patients have been enrolled, the study will be temporarily stopped to address possible changes in the manufacturing process.
Measured: Up to 12 weeks
Feasibility of delivering NK cells
Therapy will be considered feasible if at least 2/3 of subjects treated receive at least 21 of the planned 27 NK cell infusions.
Measured: Up to 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2014 (estimated)
- Study start17 Mar 2015
- Primary completion28 Aug 2020
- Study completion28 Aug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent Childhood MedulloblastomaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Soumen Khatua, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02271711
- Sponsor's protocol ID
- 2013-0765
- Other IDs
- NCI-2014-02677, 2013-0765, P30CA016672
- Status last verified
- Aug 2020
- First submitted
- 17 Oct 2014
- Last updated
- 2 Sep 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Intraventricular Infusions of Autologous Ex Vivo-Expanded NK Cells in Children With Recurrent/Refractory Malignant Posterior Fossa Tumors of the Central Nervous System. NOAH's (New Opportunity, Advancing Hope) Protocol
- ClinicalTrials.gov ID
- NCT02271711
- Acronym / sponsor ID
- 2013-0765
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 17 Mar 2015 (actual)
- Primary completion
- 28 Aug 2020 (actual)
- Study completion
- 28 Aug 2020 (actual)
- First posted
- 22 Oct 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I trial studies the side effects and best dose of expanded natural killer cells in treating younger patients with brain tumors that have come back or do not respond to treatment. Infusing a particular type of a patient's own white blood cells called natural killer cells that have been through a procedure to expand (increase) their numbers may work in treating patients with recurrent/refractory brain tumors.
Detailed description
PRIMARY OBJECTIVES:
- To establish the safety, feasibility, efficacy, and maximum tolerated dose (MTD) of administering autologous natural killer (NK) cells that have been propagated ex vivo with artificial antigen-presenting cells (aAPC) and administered directly into the ventricle in recurrent /refractory malignant posterior fossa tumors.
SECONDARY OBJECTIVES:
- To assess the antitumor activity based on imaging and cytology of autologous NK cell locoregional administration directly into the lateral or fourth ventricle.
II. To determine the persistence of adoptively-transferred expanded NK cells (as performed with excess NK cells, via optional correlative studies).
III. Determine the immunophenotype and function of expanded NK cells. IV. Determine the overall response of medulloblastoma to NK-cell therapy. V. Correlate NK cell persistence, phenotype, and function with overall response.
OUTLINE: This is a dose-escalation study.
Patients receive autologous expanded NK cells intravenously (IV) into the ventricle over 3 minutes once weekly on weeks 1-3. Treatment repeats every 4 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients experiencing disease progression may continue treatment at the discretion of the treating physician if pseudo-progression or benefit of slowed progression is suspected.
After completion of study treatment, patients are followed up within 30 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (autologous ex vivo-expanded NK cells) | Experimental | Other: Laboratory Biomarker Analysis, Biological: Natural Killer Cell TherapyPatients receive autologous expanded NK cells IV into the ventricle over 3 minutes once weekly on weeks 1-3. Treatment repeats every 4 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients experiencing disease progression may continue treatment at the discretion of the treating physician if pseudo-progression or benefit of slowed progression is suspected. |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (13 listed)
- Diagnosis: patients with recurrent/refractory medulloblastoma (MB), atypical teratoid (AT)/rhabdoid tumors (RT) or ependymoma involving the brain and/or spine at original diagnosis or relapse; they must have histological verification at diagnosis and/or relapse; patient must have presented with these tumors in the posterior fossa (PF) or relapsed in the PF
- Patient must have either measurable or evaluable tumor
- Presence of or determined by neurosurgery to be a candidate for an implanted catheter in the ventricles to receive NK cell infusion
- Life expectancy of at least 12 weeks in opinion of principal investigator (PI) and/or designee
- Lansky score of 50 or greater if =<16 years of age or a Karnofsky score of 50 or greater if > 16 years of age (NOTE: patients who are unable to walk because of paralysis, but who are in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score)
Key exclusion criteria (6 listed)
- Enrolled in another treatment protocol
- Evidence of untreated infection
- Extra-cranial metastasis
- Chronic corticosteroid dependence (except replacement therapy)
- Extensive disease, disease location, and/or co-morbid condition that the PI or designee considers unsafe for surgical intervention of NK cell infusion
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (autologous ex vivo-expanded NK cells) |
| Natural Killer Cell TherapyGiven autologous ex-vivo expanded NK cells IV | Biological | Treatment (autologous ex vivo-expanded NK cells) |
Primary outcome
Maximum tolerated dose (MTD) of natural killer (NK) cells
Time frame: 4 weeks
Defined as the highest dose studied in which 6 patients have been treated at most 1 patient with dose limiting toxicities are observed. Toxicities will be summarized by tabulation in terms of type, grade and attribution for each dose level of each group of patients studied at the end of the trial.
6 secondary outcomes
Activation status of NK cells
Time frame: Up to 30 days after the last infusion in course 3
Persistence of NK cells
Time frame: Up to 30 days after the last infusion in course 3
Function of NK cells
Time frame: Up to 30 days after the last infusion in course 3
Response of medulloblastoma to NK cells
Time frame: Up to 30 days after the last infusion in course 3
Feasibility of NK cell manufacturing
Time frame: Up to 12 weeks
Feasibility of delivering NK cells
Time frame: Up to 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2020.
- University of Texas MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Soumen Khatua principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Laboratory Biomarker Analysis and Natural Killer Cell Therapy in people with Recurrent Childhood Medulloblastoma and Recurrent Ependymoma, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (MTD) of natural killer (NK) cells (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2020.