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Ex-Vivo Expanded Allogeneic NK Cells For The Treatment Of Pediatric Solid Tumors

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ClinicalTrials.gov Identifier: NCT03420963
Recruitment Status : Recruiting
First Posted : February 2, 2018
Last Update Posted : November 26, 2018
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

Any time the words "you," "your," "I," or "me" appear, it is meant to apply to the potential participant.

NK cells are specialized immune cells in the body that have been shown to kill tumor cells (including solid tumor cells) in the laboratory. Previous studies of NK cells in some cancer patients have suggested that they can be given without severe side effects and may help in controlling tumors.

The goal of this clinical research study is to learn the recommended dose of donated natural killer cells that can be given to pediatric cancer patients with solid tumors after receiving chemotherapy (cyclophosphamide and etoposide). The safety of the NK cells given after chemotherapy will also be studied.

In this study, the NK cells being used have already been donated/collected from cord blood (blood collected at birth from the afterbirth of healthy babies). They are then "expanded," or grown, so that more NK cells can be made from a small sample and given to a patient.

Cyclophosphamide and etoposide are standard chemotherapy drugs that are used in the treatment of pediatric solid tumors. In this study, the drugs are being given both to fight the cancer cells and also to help prevent your body from rejecting the NK cells.

This is an investigational study. NK cell transplants are not FDA approved or commercially available. Cyclophosphamide and etoposide are FDA approved and commercially available for the treatment being used on this study. The use of NK cell transplants in combination with this chemotherapy is investigational.

The study doctor can describe how the study drugs and NK cells are designed to work.

Up to 32 participants will be enrolled on this study. All will take part at MD Anderson.


Condition or disease Intervention/treatment Phase
Malignant Neoplasms of Bone and Articular Cartilage Malignant Neoplasms of Female Genital Organs Malignant Neoplasms of Independent (Primary) Multiple Sites Malignant Neoplasms of Lip Oral Cavity and Pharynx Malignant Neoplasms of Male Genital Organs Malignant Neoplasms of Mesothelial and Soft Tissue Malignant Neoplasms of Thyroid and Other Endocrine Glands Malignant Neoplasms of Urinary Tract Melanoma and Other Malignant Neoplasms of Skin Drug: Cyclophosphamide Drug: Etoposide Procedure: NK Cell Infusion Drug: Mesna Phase 1

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Ex-Vivo Expanded Allogeneic NK Cells For The Treatment Of Solid Tumors Of Pediatric Origin In Children And Young Adults
Actual Study Start Date : August 31, 2018
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: NK Cells + Chemotherapy

Participants assigned to a dose level of NK cells based on when study is joined. Up to 2 dose levels of NK cells will be tested. Once the maximum tolerated dose is reached, expansion phase begins.

Participants receive cyclophosphamide and etoposide by vein over about 30 minutes on Days 1-5. Participants then receive NK cells by vein on Day 8.

Mesna will start with dose prior to cyclophosphamide and then 3 and 6 hours after each dose for total of at least 80% of cyclophosphamide dose.

Drug: Cyclophosphamide
500 mg/m2 by vein on Days -7 to -3.
Other Names:
  • Cytoxan
  • Neosar

Drug: Etoposide
100 mg/m2 by vein on Days -7 to -3.
Other Name: VePesid

Procedure: NK Cell Infusion

Participants receive NK infusion on Day 0.

Participants assigned to a dose level of NK cells based on when study is joined. Up to 2 dose levels of NK cells will be tested. Once the maximum tolerated dose is reached, expansion phase begins.


Drug: Mesna
MESNA will start with dose prior to cyclophosphamide and then 3 and 6 hours after each dose for total of at least 80% of cyclophosphamide dose.
Other Name: Mesnex




Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) of NK Cells with Chemotherapy [ Time Frame: 30 days after NK infusion ]

    MTD defined as the highest dose level for the combination therapy with no more than 1 out of 6 patients experiencing dose limiting toxicity (DLT).

    DLT determined by adverse events and graded according to the Common Terminology Criteria v4.03 (CTCAE).



Secondary Outcome Measures :
  1. Disease Response of NK Cells with Chemotherapy [ Time Frame: 30 days after NK infusion ]
    Response determined by a modified (RECIST 1.1) Response Evaluation Criteria in Solid Tumor from the NCI that has been further modified for immune-related therapy trials (irRECIST).

  2. Persistence of Adoptively-Transferred Cord NK Cells After Solid Tumor Directed Chemotherapy [ Time Frame: 30 days after NK infusion ]
    Determination of NK cell persistence estimated using two-sample t-test/Wilcoxon sum-rank test.

  3. Persistence of Adoptively-Transferred Cord NK Cells After Solid Tumor Directed Chemotherapy [ Time Frame: 30 days after NK infusion ]
    Determination of NK cell persistence estimated using ANOVA/Kruskal-Wallis test.



Information from the National Library of Medicine

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Ages Eligible for Study:   12 Months to 40 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Screening inclusion criteria: Patient age between 12 months and 40 years, inclusive at the time of study entry.
  2. Screening inclusion criteria: Patients with relapsed or refractory solid tumors and without known curative therapy or therapy proven to proven to prolong survival with acceptable quality of life.
  3. Screening inclusion criteria: Patients older than 21 years must have a solid tumor considered by study doctor to be of the childhood cancer type.
  4. Screening inclusion criteria: Performance level as measured by Karnofsky >/=60% for patients > 16 years of age or Lansky >/= 60% for patients </= 16 years of age.
  5. Screening inclusion criteria: Documentation of measurable or evaluable non-measurable disease.
  6. Screening inclusion criteria: At least one documented histological verification of solid tumor diagnosis. Can be from original diagnosis or more recent.
  7. Enrollment inclusion criteria: Patient must have fully recovered (i.e. returned to baseline) from the clinically significant acute treatment-related toxicities of all prior treatments prior to beginning treatment on this protocol with exceptions of cytopenias resulting from persistent disease, hearing loss and alopecia.
  8. Enrollment inclusion criteria: Performance level as measured by Karnofsky >/= 60% for patients > 16 years of age or Lansky >/= 60% for patients </= 16 years of age.
  9. Enrollment inclusion criteria: Adequate renal function defined as: Creatinine clearance >/= 60 mL/min/1.73m2 (calculated by 24h urine collection or nuclear GFR scan if 24h collection is not possible) or a serum creatinine based on age and gender as follows: Age 1 month to < 6 months, Maximum Serum Creatinine (mg/dL) Male 0.4, Female 0.4; 6 months to < 1 year, 0.5, 0.5; 1 to < 2 years, 0.6, 0.6; 2 to < 6 years, 0.8, 0.8; 6 to < 10 years, 1, 1; 10 to < 13 years, 1.2, 1.2; 13 to < 16 years, 1.5, 1.4; >/= 16 years, 1.7, 1.4.
  10. Enrollment inclusion criteria: Adequate liver function, defined as: total bilirubin </= 2 mg/dl and SGPT (ALT) </= 2.5 x ULN for age (unless Gilbert's disease or abnormal liver function due to primary disease).
  11. Enrollment inclusion criteria: Evidence of adequate bone marrow function (defined by ANC >/= 750 and Platelets >/=50,000), unless patient has documented tumor metastasis to the bone marrow or other condition that results in cytopenia without abnormal marrow function.
  12. Enrollment inclusion criteria: Pulmonary symptoms controlled by medication and pulse oximetry >/= 92% on room air.
  13. Enrollment inclusion criteria: Sexually active males and females of childbearing potential must agree to use a form of contraception considered effective and medically acceptable by the Investigator. (Non-childbearing potential defined as pre-menarche, greater than one year post-menopausal or surgically sterilized).
  14. Enrollment inclusion criteria: Confirmation that a cord blood donor which is matched with the recipient at a 4, 5, or 6/6 HLA class I (serological) and HLA class II (molecular) antigens.
  15. Enrollment inclusion criteria: Signed Informed Consent and if applicable pediatric assent.

Exclusion Criteria:

  1. Screening exclusion criteria: Primary tumors of the central nervous system.
  2. Screening exclusion criteria: Chronic corticosteroid dependence that is unable to be weaned to discontinue.
  3. Screening exclusion criteria: Determined by study doctor that patient is unlikely to meet inclusion criteria after screening.
  4. Enrollment exclusion criteria: Uncontrolled arrhythmias or uncontrolled symptoms of cardiac disease noted by screening history and physical. Patients with known cardiac dysfunction should have an EF > 40% documented by ECHO.
  5. Enrollment exclusion criteria: Patients where the burden of pulmonary metastasis, location, or bulkiness of disease may cause high morbidity if localized swelling such as causing uncontrolled symptoms, oxygen dependence, or location near a major bronchi as determined by investigator.
  6. Enrollment exclusion criteria: Pregnant females.
  7. Any uncontrolled systemic infection

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03420963


Contacts
Contact: Jessica S. Foglesong, MD 713-792-6620 jsfoglesong@mdanderson.org

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact       jsfoglesong@mdanderson.org   
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Jessica S. Foglesong, MD M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03420963     History of Changes
Other Study ID Numbers: 2017-0085
NCI-2018-00909 ( Registry Identifier: NCI CTRP )
First Posted: February 2, 2018    Key Record Dates
Last Update Posted: November 26, 2018
Last Verified: November 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Natural killer cells
NK cells
Cyclophosphamide
Cytoxan
Neosar
Etoposide
VePesid

Additional relevant MeSH terms:
Neoplasms
Genital Neoplasms, Female
Genital Neoplasms, Male
Urologic Neoplasms
Bone Neoplasms
Lip Neoplasms
Thyroid Neoplasms
Cartilage Diseases
Soft Tissue Neoplasms
Neoplasms, Fibrous Tissue
Skin Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Bone Diseases
Musculoskeletal Diseases
Mouth Neoplasms
Head and Neck Neoplasms
Lip Diseases
Mouth Diseases
Stomatognathic Diseases
Endocrine Gland Neoplasms
Endocrine System Diseases
Thyroid Diseases
Connective Tissue Diseases
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Skin Diseases
Cyclophosphamide