AzTrials
AzTrials

Platinum-resistant Ovarian CancerPhase 1NCT06321484

Intraperitoneal Cytokine-Induced Memory Like (CIML) Natural Killer (NK) Cells in Recurrent Ovarian Cancer

A Phase 1 study testing Cytokine-Induced Memory-like Natural Killer Cells and Interleukin 2 in people with Platinum-resistant Ovarian Cancer and Recurrent Ovary Cancer, run by Dana-Farber Cancer Institute at 2 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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) Read more about this study

Who is it for?
Ages 18 to 85 years
What is being tested?
Cytokine-Induced Memory-like Natural Killer Cells and Interleukin 2
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
2 sitesUnited States
Study dates
9 Oct 2024to 31 Oct 2031
Phase
Phase 1
Are there results?
Not yet: the study is under way

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 18 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • 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.
  • ECOG performance status of 0 or 1.
  • Participants must meet the following organ and marrow function as defined below:
Show all 19Show fewer
  • 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.
  • Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants should be class 2B or better.
  • Physician assessment indicating the patient would be able to tolerate undergoing a brief procedure for placement of an intraperitoneal port for NK cell infusion.
  • Ability to understand and the willingness to sign a written informed consent document.
  • The effects of CIML NK cells and IL-2 on the developing human fetus are unknown. For this reason and because CIML NK cells and IL-2 may be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.

Who cannot join

  • 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.
  • 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 CIML NK cells or IL-2 or any of the other agents used in study.
Show all 16Show fewer
  • 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).
  • 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 IL-2 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 IL-2, 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.
  • Prior history of Grade 2 or higher hemolytic anemia (>/= 2g decrease in hemoglobin plus laboratory evidence of hemolysis) from any cause.

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

DFCI Clinical Trials Hotline DFCI Clinical Trials Hotline contact

877-DF-TRIAL

rebecca_porter@dfci.harvard.edu

Rebecca Porter, MD, PhD contact

(617) 632-5269

rebecca_porter@dfci.harvard.edu

United States2 sites, 2 recruiting

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02215

    Rebecca Porter, MD, PhD, 617-632-2334, rebecca_porter@dfci.harvard.edu

    Rebecca Porter, MD, PhD

    Not yet recruiting

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

    Rebecca Porter, MD, PhD, 617-632-2334, Rebecca_Porter@dfci.harvard.edu

    Rebecca Porter, MD, PhD

    Recruiting

Other trials in United States

About this study

Official title: A Phase 1b Study of Cytokine-Induced Memory Like (CIML) Natural Killer (NK) Cell Therapy in Recurrent Ovarian Cancer

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)

Read the detailed description

This is an open-label, single site, phase 1b study 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.

Participants will be enrolled to test the safety of intraperitoneal CIML NK cell therapy

The U.S. Food and Drug Administration (FDA) has not approved CIML NK cell therapy as a treatment for recurrent, high grade ovarian cancer.

The research study procedures include screening for eligibility, collection of natural killer (NK) cells in a process called leukapheresis, lymphodepleting chemotherapy, infusion of CIML NK cell therapy into the abdominal cavity (intraperitoneal), administration of low-dose IL-2, Computerized Tomography (CT) scans, Magnetic Resonance Imaging (MRI), or Positron Emission Tomography (PET) scans, blood tests, urine tests, electrocardiograms (ECGs), and echocardiograms.

Participants in this research study will be followed for up to for 5 years after start of study treatment.

It is expected that about 12-18 people will take part in this research study.

The PHASE ONE Foundation Community Research Grant is providing funding for this research study.

Being tested
Cytokine-Induced Memory-like Natural Killer Cells, Interleukin 2
Keywords
Platinum-Resistant Ovarian Cancer, Recurrent Ovary Cancer, Ovarian Cancer, Ovarian Carcinoma, Ovarian Carcinoma, Recurrent, Endometroid Ovarian Carcinoma, Clear Cell Ovarian Carcinoma
Medical subject headings
Ovarian Neoplasms, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cytokine-Induced Memory-like Natural Killer CellsBiological

    Also called CIML NK Cells

    Cytokine Induced Memory-like Natural Killer (CIML NK) Cells Autologous, cytokine induced memory-like natural killer cells, via intraperitoneal (IP) infusion per protocol.

  • Interleukin 2Drug

    Low dose subcutaneous IL-2 will be administered every other day for 5 doses after CIML NK cell infusion

Study groups in NCT06321484
Study groupRoleWhat they receive
Dose Level 0ExperimentalParticipants 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.
Receives: Biological: Cytokine-Induced Memory-like Natural Killer Cells; Drug: Interleukin 2
Dose Level -1Experimental3+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.
Receives: Biological: Cytokine-Induced Memory-like Natural Killer Cells; Drug: Interleukin 2

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 60 days

  2. 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.

    Measured: 60 days

Secondary outcomes (5)

  1. Overall Response Rate (ORR)

    ORR is defined as the proportion of participants who achieved partial response or complete response during study treatment based on RECIST 1.1 and immune-related RECIST criteria.

    Measured: Up to 5 years

  2. Median Progression Free Survival (PFS)

    PFS is defined as the time from registration to the earlier of progression (PD) or death due to any cause based on Kaplan-Meier methodology. Participants alive without disease progression are censored at date of last disease evaluation.

    Measured: Up to 5 years

  3. Clinical Benefit Rate (CBR)

    CBR is defined as the proportion of participants who achieved a complete response, partial response, or had stable disease for 6 months or more based on RECIST 1.1 and immune-related RECIST criteria.

    Measured: Up to 5 years

  4. Duration of Response (DOR)

    DOR is measured from the time measurement criteria are met for complete response or partial response (whichever is first recorded) until the first data that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started, or death due to any cause. Participants without events reported are censored at the last disease evaluation.

    Measured: Up to 5 years

  5. 6 months Progression Free Survival (PFS6)

    PFS6 is the percent probability estimate at 6 months based on the Kaplan-Meier method. PFS is defined as the time from registration to the earlier of progression (PD) or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation.

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Mar 2024
  2. Study start9 Oct 2024
  3. Primary completion30 Nov 2026 (estimated)
  4. Study completion31 Oct 2031 (estimated)

Resources

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
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
18 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06321484
Sponsor's protocol ID
23-493
Status last verified
Jun 2026
First submitted
30 Oct 2023
Last updated
16 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cytokine-Induced Memory-like Natural Killer Cells and Interleukin 2 in people with Platinum-resistant Ovarian Cancer and Recurrent Ovary Cancer, run by Dana-Farber Cancer Institute at 2 sites 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 19 inclusion and 16 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: looking for participants now, as of the sponsor's last update on 16 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact DFCI Clinical Trials Hotline DFCI Clinical Trials Hotline (877-DF-TRIAL, rebecca_porter@dfci.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD) (Cohort 1) (time frame: 60 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06321484.

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 16 Jun 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in