Trial Title:
Intraperitoneal Cytokine-Induced Memory Like (CIML) Natural Killer (NK) Cells in Recurrent Ovarian Cancer
NCT ID:
NCT06321484
Condition:
Platinum-resistant Ovarian Cancer
Recurrent Ovary Cancer
Ovarian Cancer
Ovarian Carcinoma
Ovarian Carcinoma, Recurrent
Conditions: Official terms:
Carcinoma
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Recurrence
Interleukin-2
Conditions: Keywords:
Platinum-Resistant Ovarian Cancer
Recurrent Ovary Cancer
Ovarian Cancer
Ovarian Carcinoma
Ovarian Carcinoma, Recurrent
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Cytokine-Induced Memory-like Natural Killer Cells
Description:
Cytokine Induced Memory-like Natural Killer (CIML NK) Cells Autologous, cytokine induced
memory-like natural killer cells, via intraperitoneal (IP) infusion per protocol.
Arm group label:
Dose Level -1
Arm group label:
Dose Level 0
Other name:
CIML NK Cells
Intervention type:
Drug
Intervention name:
Interleukin 2
Description:
Low dose subcutaneous IL-2 will be administered every other day for 5 doses after CIML NK
cell infusion
Arm group label:
Dose Level -1
Arm group label:
Dose Level 0
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)
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Participants must have histologically or cytologically confirmed recurrent
epithelial ovarian cancer. Eligible histologies include high grade endometrioid or
high grade serous ovarian carcinoma.
- Participants must have measurable cancer defined by RECIST 1.1 criteria. Recurrent
cancer must be isolated to the abdomen or pelvis with no obvious extra-abdominal
metastases via radiographic imaging or physical exam. See Section 12 (Measurement of
Effect) for the evaluation of measurable disease.
- Patients must have received at least 3 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.
- 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. (Providing consents in as many languages as possible is encouraged)
- The effects of CIML NK cells and N-803 on the developing human fetus are unknown.
For this reason and because CIML NK cells and N-803 are known to 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. Should a woman become pregnant or suspect
she is pregnant while she or her partner is participating in this study, she should
inform her treating physician immediately.
Exclusion Criteria:
- Participants with distant metastasis outside of the abdominopelvic cavity (e.g.,
central nervous system, pulmonary, osseous, etc.) whereby intraperitoneal treatment
would potentially have minimal effect.
- 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.
- Prior history of Grade 2 or higher hemolytic anemia (>/= 2g decrease in hemoglobin
plus laboratory evidence of hemolysis) from any cause.
Gender:
All
Minimum age:
18 Years
Maximum age:
85 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Brigham and Women's Hospital
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Rebecca Porter, MD, PhD
Phone:
(617) 632-2334
Email:
rebecca_porter@dfci.harvard.edu
Contact backup:
Last name:
Rebecca Porter, MD, PhD
Facility:
Name:
Dana-Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Contact:
Last name:
Rebecca Porter, MD, PhD
Phone:
617-632-2334
Email:
Rebecca_Porter@dfci.harvard.edu
Contact backup:
Last name:
Rebecca Porter, MD, PhD
Start date:
October 9, 2024
Completion date:
October 31, 2031
Lead sponsor:
Agency:
Dana-Farber Cancer Institute
Agency class:
Other
Collaborator:
Agency:
ImmunityBio, Inc.
Agency class:
Industry
Source:
Dana-Farber Cancer Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06321484