Intraperitoneal Cytokine-Induced Memory Like (CIML) Natural Killer (NK) Cells in Recurrent Ovarian Cancer
A Phase 1b Study of Cytokine-Induced Memory Like (CIML) Natural Killer (NK) Cell Therapy in Recurrent Ovarian Cancer
1 other identifier
interventional
18
1 country
2
Brief Summary
The goal of this research study is to evaluate the safety and effectiveness of the use of cytokine-induced memory-like (CIML) natural killer (NK) cell therapy in recurrent, high grade ovarian cancer (HGOC). Names of the study therapies involved in this study are: CIML NK (cellular therapy) Interleukin-2 (IL-2)
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Oct 2024
Longer than P75 for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 30, 2023
CompletedFirst Posted
Study publicly available on registry
March 20, 2024
CompletedStudy Start
First participant enrolled
October 9, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 30, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
October 31, 2031
March 4, 2026
March 1, 2026
2.1 years
October 30, 2023
March 2, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Maximum Tolerated Dose (MTD) (Cohort 1)
The MTD of the use of cytokine induced memory-like natural killer (CIML NK) cell therapy is determined by the number of participants who experience a dose limiting toxicity (DLT). See subsequent primary outcome measure for DLT definition.
60 days
Dose Limiting Toxicity (DLT) (Cohort 1)
A DLT is defined as an adverse event that is related to CIML NK cell therapy with an attribution of possible, probable, or definite, and meets the criteria defined in protocol section 5.4.
60 days
Secondary Outcomes (5)
Overall Response Rate (ORR)
Up to 5 years
Median Progression Free Survival (PFS)
Up to 5 years
Clinical Benefit Rate (CBR)
Up to 5 years
Duration of Response (DOR)
Up to 5 years
6 months Progression Free Survival (PFS6)
6 months
Study Arms (2)
Dose Level 0
EXPERIMENTALParticipants will be enrolled in a staggered fashion into a 3+3 dose de-escalation per protocol to establish a maximum tolerated dose (MTD). Dosage will start at dose level 0. * Baseline visit. * MRIs, PET scans, and/or CT scans every 8 weeks. * Cycle 0: * Day -7 of 8 day cycle: Apheresis for autologous NK cell collection. * Days -6 through -2 of 8 day cycle: Predetermined dose of lymphodepleting chemotherapy per protocol. * Days -5 through -4 of 8 day cycle: * Predetermined dose of lymphodepleting chemotherapy per protocol. * Predetermined dose of premedication per institutional standards. * Day 0 of 8 day cycle: * Predetermined dose of CIML NK cells once * Subcutaneous low-dose IL-2 once * Cycle 1: \- Days 2-8: Subcutaneous low-dose IL-2 every other day for 4 additional doses * Off-Treatment: * Long-term follow up for 5 years after last CIML NK cell infusion.
Dose Level -1
EXPERIMENTAL3+3 de-escalation to dose level -1 per protocol if DLTs occur in Cohort 1 dose Level 0. * Baseline visit. * MRIs, PET scans, and/or CT scans every 8 weeks. * Cycle 0: * Day -7 of 8 day cycle: Apheresis for autologous NK cell collection. * Days -6 through -2 of 8 day cycle: Predetermined dose of lymphodepleting chemotherapy per protocol. * Days -5 through -4 of 8 day cycle: * Predetermined dose of lymphodepleting chemotherapy per protocol. * Predetermined dose of premedication per institutional standards. * Day 0 of 8 day cycle: * Predetermined dose of CIML NK cells once * Subcutaneous low-dose IL-2 once * Cycle 1: \- Days 2-8: Subcutaneous low-dose IL-2 every other day for 4 additional doses * Off-Treatment: * Long-term follow up for 5 years after last CIML NK cell infusion.
Interventions
Cytokine Induced Memory-like Natural Killer (CIML NK) Cells Autologous, cytokine induced memory-like natural killer cells, via intraperitoneal (IP) infusion per protocol.
Low dose subcutaneous IL-2 will be administered every other day for 5 doses after CIML NK cell infusion
Eligibility Criteria
You may qualify if:
- Participants must have histologically or cytologically confirmed recurrent epithelial ovarian cancer. Eligible histologies include high grade serous, high grade endometrioid and clear cell ovarian carcinoma.
- Participants must have measurable cancer defined by RECIST 1.1 criteria. See Section 12 (Measurement of Effect) for the evaluation of measurable disease.
- Patients must have received at least 1 lines of prior systemic therapy and be deemed platinum resistant/intolerant by their treating oncologist. Patients with germline or somatic BRCA1 or BRCA2 mutations must have received prior PARP inhibitor therapy as maintenance or treatment. Prior receipt of immune checkpoint blockade is allowed if grade 3 or higher toxicities were not experienced.
- Age ≥18 years and \<85 years old. Because no dosing or adverse event data are currently available on the use of CIML NK cells in combination with N-803 in participants \<18 years of age, children are excluded from this study.
- ECOG performance status of 0 or 1 (see Appendix A).
- Participants must meet the following organ and marrow function as defined below:
- Absolute neutrophil count ≥1,000/mcL
- Platelets ≥75,000/mcL
- AST(SGOT)/ALT(SGPT) ≤3 x institutional ULN
- Total bilirubin ≤1.5 x institutional upper limit of normal (ULN) (except Gilbert's or disease-related hemolysis, then \< 3 x ULN)
- Serum creatinine ≤ 2.0 mg/dL OR glomerular filtration rate (GFR) ≥40 mL/min/1.73 m2
- Oxygen saturation: ≥ 90% on room air
- Left ventricular ejection fraction (cardiac function) ≥ 40%
- No laboratory evidence of ongoing hemolysis in opinion of investigator
- Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
- +4 more criteria
You may not qualify if:
- Participants who have had anti-tumor chemotherapy or other investigational agents within two weeks prior to NK cell infusion (6 weeks for nitrosoureas or mitomycin C), or immunotherapy within 6 weeks prior, or those who have not recovered from adverse events due to agents administered more than two weeks prior. The intent of the language is to ensure that anti-tumor chemotherapy or other investigational agents are not administered to subjects within the specified window since the can potentially affect NK cell activity. Therefore, the washout period is defined by time from NK cell infusion and not patient enrollment. During eligibility confirmation from the study team is requested to confirm that according to the planned NK cell dosing schedule, the washout period should be completed, based on each drug class.
- Participants with a bowel obstruction within the last 3 months or high risk for bowel obstruction (in the opinion of the investigator) or current need for parenteral nutrition or dependence on intravenous fluids.
- Participants who are receiving any other investigational agents.
- Solid organ transplant (allograft) recipients.
- Participants with known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years of the first dose of study treatment with the exception of cured basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other non-invasive or indolent malignancy, or cancers from which the patient has been disease-free for \> 1 year after treatment with curative intent.
- History of severe or anaphylactic allergic reactions attributed to compounds of similar chemical or biologic composition to N-803 or any of the other agents used in study.
- For patients with prior exposure to check point inhibitor therapy, those with a prior history of immune-related toxicity during immune therapy that resulted in permanent discontinuation of therapy (as recommended per product label or consensus guidelines) OR any immune-related toxicity requiring intensive or prolonged immunosuppression to manage (with the exception of endocrinopathy that is well-controlled on replacement hormones) are excluded.
- Autoimmune disease: patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's disease, are excluded from this study, as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus, autoimmune vasculitis \[Wegener's granulomatosis\]) and motor neuropathy considered of autoimmune origin (e.g., GuillainBarre syndrome and myasthenia gravis). Patients with Hashimoto thyroiditis are eligible.
- Systemic corticosteroid therapy (\> 10 mg of prednisone or equivalent dose of systemic steroids for at least 4 weeks prior to NK cell infusion). The intent of this language is to ensure that systemic steroids are not administered to subjects within the specified window since this can potentially affect NK cell activity. Therefore, the washout period is defined by time from NK cell infusion and not patient enrollment. During eligibility confirmation the study team is requested to confirm that according to the planned NK cell dosing schedule, the washout period should be completed.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant women are excluded from this study because of the unknown teratogenic risk of CIML NK cells and NIZ985 and with the potential for teratogenic or abortifacient effects by fludarabine/cyclophosphamide chemotherapy regimen. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with CIML NK cells and NIZ985, breastfeeding should be discontinued if the mother is treated on this study.
- HIV-positive participants are ineligible because of the potential for pharmacokinetic interactions with anti-retroviral agents used in this study. In addition, these participants are at increased risk of lethal infections when treated with marrow-suppressive therapy.
- Individuals with active uncontrolled hepatitis B or C are ineligible as they are at high-risk of lethal treatment-related hepatotoxicity in the setting of marrow suppression. Known non-infectious pneumonitis or any history of interstitial lung disease.
- Receipt of a live vaccine within 30 days of start of study treatment. During eligibility confirmation the study team is requested to confirm that according to the planned NK cell dosing schedule, the washout period should be completed.
- Anaphylactic reactions to murine-based antibody therapy or iron dextran as the CIML NK cell product contains similar reagents at end of manufacturing/infusion.
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
Brigham and Women's Hospital
Boston, Massachusetts, 02215, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Rebecca Porter, MD, PhD
Dana-Farber Cancer Institute
Central Study Contacts
DFCI Clinical Trials Hotline DFCI Clinical Trials Hotline
CONTACT
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
October 30, 2023
First Posted
March 20, 2024
Study Start
October 9, 2024
Primary Completion (Estimated)
November 30, 2026
Study Completion (Estimated)
October 31, 2031
Last Updated
March 4, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- Data can be shared no earlier than 1 year following the date of publication
- Access Criteria
- Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu
The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.