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Expanded Natural Killer Cell Infusion in Treating Younger Patients With Recurrent/Refractory Brain Tumors

Primary Purpose

Recurrent Childhood Medulloblastoma, Recurrent Ependymoma, Recurrent Medulloblastoma

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Laboratory Biomarker Analysis

Natural Killer Cell Therapy

About this trial

This is an interventional treatment trial for Recurrent Childhood Medulloblastoma

Eligibility Criteria

undefined - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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
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

Exclusion Criteria:

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

Sites / Locations

M D Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (autologous ex vivo-expanded NK cells)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

Function of NK cells

Assessed by cell lysis of standardized targets.

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.

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.

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.

Full Information

NCT ID

NCT02271711

First Posted

October 17, 2014

Last Updated

August 31, 2020

Sponsor

M.D. Anderson Cancer Center

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT02271711

Brief Title

Expanded Natural Killer Cell Infusion in Treating Younger Patients With Recurrent/Refractory Brain Tumors

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2020

Overall Recruitment Status

Completed

Study Start Date

March 17, 2015 (Actual)

Primary Completion Date

August 28, 2020 (Actual)

Study Completion Date

August 28, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

M.D. Anderson Cancer Center

Collaborators

National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief 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. 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: I. 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: I. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Recurrent Childhood Medulloblastoma, Recurrent Ependymoma, Recurrent Medulloblastoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

12 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment (autologous ex vivo-expanded NK cells)

Arm Type

Experimental

Arm Description

Intervention Type

Other

Intervention Name(s)

Laboratory Biomarker Analysis

Intervention Description

Correlative studies

Intervention Type

Biological

Intervention Name(s)

Natural Killer Cell Therapy

Intervention Description

Given autologous ex-vivo expanded NK cells IV

Primary Outcome Measure Information:

Title

Maximum tolerated dose (MTD) of natural killer (NK) cells

Description

Time Frame

4 weeks

Secondary Outcome Measure Information:

Title

Activation status of NK cells

Description

Determined by flow-based activation assay determining cluster of differentiation (CD)107a expression of NK cells in response to standardized targets.

Time Frame

Up to 30 days after the last infusion in course 3

Title

Persistence of NK cells

Description

Peripheral blood and cerebrospinal fluid (CSF) will be obtained before therapy, during the NK cell treatment period, and after NK cell treatment.

Time Frame

Up to 30 days after the last infusion in course 3

Title

Function of NK cells

Description

Assessed by cell lysis of standardized targets.

Time Frame

Up to 30 days after the last infusion in course 3

Title

Response of medulloblastoma to NK cells

Description

Time Frame

Up to 30 days after the last infusion in course 3

Title

Feasibility of NK cell manufacturing

Description

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.

Time Frame

Up to 12 weeks

Title

Feasibility of delivering NK cells

Description

Therapy will be considered feasible if at least 2/3 of subjects treated receive at least 21 of the planned 27 NK cell infusions.

Time Frame

Up to 12 weeks

10. Eligibility

Sex

All

Maximum Age & Unit of Time

21 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 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 Exclusion Criteria: 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Soumen Khatua

Organizational Affiliation

M.D. Anderson Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

M D Anderson Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

12. IPD Sharing Statement

Links:

URL

http://www.mdanderson.org

Description

University of Texas MD Anderson Cancer Center Website

Learn more about this trial

Expanded Natural Killer Cell Infusion in Treating Younger Patients With Recurrent/Refractory Brain Tumors

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