COL6A3 PositivePhase 1/2NCT03318900

T-Cell Infusion, Aldesleukin, and Utomilumab in Treating Patients With Recurrent Ovarian Cancer

A Phase 1/2 study testing Aldesleukin, CD8-Positive T-Lymphocyte and Cyclophosphamide in people with COL6A3 Positive and HLA-A*0201 Positive Cells Present, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 to 75 years, women only
Conditions the study is for: COL6A3 Positive, HLA-A*0201 Positive Cells Present, PRAME Positive
What is being tested?: Aldesleukin, CD8-Positive T-Lymphocyte and Cyclophosphamide
Type of treatment: Injection or infusion, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 5 participants
Where: 1 siteUnited States
Study dates: 4 Sep 2018to 20 Dec 2023
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 75 years
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

Histopathologic documentation (must be performed or reviewed at MD Anderson) of recurrent high grade epithelial ovarian cancer.
At least one prior line of platinum-based chemotherapy (subjects are eligible for enrollment and leukapheresis while still platinum-sensitive, however, they must have developed platinum resistant disease for treatment (turnstile 2).
Tumor expressing PRAME and/or COL6A3.
Expression of HLA-A*0201.
Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
Expected survival of greater than 16 weeks.

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Willing and able to give informed consent.
Hemoglobin >= 9.0 g/dL.
Absolute neutrophil count (ANC) >= 1.0 x 10^9/L (>=1000 per mm^3).
Platelet count >= 75 x 10^9/L (>=100,000 per mm^3).
Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN) unless diagnosed with Gilbert's syndrome.
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN unless liver metastases are present, in which case it must be =< 5x ULN.
Serum creatinine clearance (CL) >40 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance.
Subjects must either be of non-reproductive potential (i.e., post-menopausal by history: >= 50 years old and no menses for >=1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.
Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study in such a manner that the risk of pregnancy is minimized. Suggested precautions should be used to minimize the risk or pregnancy for at least 1 month before start of therapy, and while women are on study for up to 3 months after T cell infusion, and at least 8 weeks after the study drug is stopped.
{Turnstile 2} Subjects must have platinum resistant disease (progression on a platinum-containing regimen or recurrence within 180 days of last dose of platinum-containing chemotherapy). Subjects that are not platinum resistant but are deemed not to be candidates for platinum-based chemotherapy due to prior significant allergic reaction may participate with principal investigator (PI) approval.
{Turnstile 2} Bi-dimensionally measurable disease by radiographic imaging (magnetic resonance imaging [MRI] or computed tomography [CT] scan).
{Turnstile 2} At least 4 weeks must have elapsed since the last chemotherapy, immunotherapy, radiotherapy or major surgery. At least 6 weeks for bevacizumab.
{Turnstile 2} Toxicity related to prior therapy must either have returned to =< grade 1, baseline, or been deemed irreversible.

Who cannot join

Clinically significant pulmonary dysfunction, as determined by medical history and physical exam. Patients so identified will undergo pulmonary functions testing and those with forced expiratory volume in one second (FEV1) < 60% of normal or carbon monoxide diffusing capacity (DLco) (corrected [corr] for hemoglobin [Hgb]) < 55% will be excluded.
Significant cardiovascular abnormalities including any one of the following: Congestive heart failure, Clinically significant hypotension, symptoms of coronary artery disease, presence of cardiac arrhythmias on electrocardiography (EKG) requiring drug therapy; or patients with a history of cardiovascular disease. (Patients with the above will undergo a cardiac evaluation which can include a stress test and/or echocardiography. Results of this evaluation will be considered before excluding patients on the basis of cardiovascular abnormalities). Subjects with evidence of stress-induced cardiac ischemia or ejection fraction less than 55% will be excluded.
History of central nervous system (CNS) metastasis.
Autoimmune disease: patients with a history of inflammatory bowel disease are excluded from this study, as are patients with a history of autoimmune disease (e.g. systemic lupus erythematosus, vasculitis, infiltrating lung disease) whose possible progression during treatment would be considered by the Investigator to be unacceptable.
{Turnstile 2} Participation in another clinical study with an investigational product administered during the last 28 days.
{Turnstile 2} Receipt of the last dose of previous chemotherapy, hormonal, or biologic treatment for ovarian, fallopian tube, or primary peritoneal cancer in the last 28 days (in the last 6 weeks for bevacizumab).

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{Turnstile 2} Current or prior use of immunosuppressive medication within 28 days before enrollment, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
{Turnstile 2} Any prior grade >= 3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE > grade 1.
History of allogeneic organ transplant.
Unresolved partial or complete small or large bowel obstruction.
{Turnstile 2} Receipt of live attenuated vaccination within 30 days prior to enrollment or within 30 days of planned lymphodepletion.
Any underlying medical or psychiatric condition, which in the opinion of the investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events.
Active viral hepatitis.
Confirmed human immunodeficiency virus (HIV) infection.

Trial locations and contacts

1 site in 1 country.

United States1 site

M D Anderson Cancer Center
Houston, Texas, 77030

Other trials in United States

About this study

Official title: Phase I/Ib Study of Adoptive Cellular Therapy Using Autologous IL-21-Primed CD8+ Tumor Antigen-Specific T Cells in Combination With Utomilumab (PF-05082566) in Patients With Platinum Resistant Ovarian Cancer

This phase I/Ib trial studies the side effects and best dose of utomilumab and how well it works with CD8-positive T-lymphocyte (T-cell infusion) and aldesleukin in treating patients with ovarian cancer that has come back. Aldesleukin may stimulate white blood cells to kill ovarian cancer cells. Giving white blood cells (T-cells) that have been activated by a vaccine with aldesleukin may kill more tumor cells. Immunotherapy with utomilumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving T-cell infusion with aldesleukin and utomilumab may work better in treating patients with ovarian cancer.

Read the detailed description

PRIMARY OBJECTIVES:

Assess the safety and toxicity of adoptively transferred central memory-type CTL targeting ovarian cancer antigens administered alone, and in combination with, utomilumab, an agonistic anti-CD137 antibody, in patients with platinum-resistant ovarian cancer.

II. Evaluate the functional and numeric in vivo persistence of adoptively transferred central memory-type CTL with and without utomilumab.

SECONDARY OBJECTIVES:

Evaluate the anti tumor effect of adoptively transferred central memory-type CTL targeting ovarian cancer antigens as measured by best overall response rate (BORR) and progression free survival (PFS).

OUTLINE: This is a dose escalation study of utomilumab.

Patients undergo leukapheresis. Patients then receive cyclophosphamide intravenously (IV) on day -2, CD8-positive T-lymphocyte via infusion on day 0, and aldesleukin subcutaneously (SC) every 12 hours for 14 days. Beginning 24 hours after CD8-positive T-lymphocyte, patients also receive utomilumab IV over 90 minutes on days 1, 29, 57, 85, 113, and 141 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at days 3, 7, 14, 22, 28, 35, 43, 49, 56, 64, 70, 77, 84, 112, and 140.

Conditions: COL6A3 Positive, HLA-A*0201 Positive Cells Present, PRAME Positive, Recurrent Ovarian Carcinoma
Being tested: Aldesleukin, CD8-Positive T-Lymphocyte, Cyclophosphamide, Leukapheresis, Utomilumab
Medical subject headings: Ovarian Neoplasms

What participants receive

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

AldesleukinBiological
Also called 125-L-Serine-2-133-interleukin 2, Proleukin, r-serHuIL-2, Recombinant Human IL-2
Given IV
CD8-Positive T-LymphocyteDrug
Also called CD8 Cell, CD8 Lymphocyte, CD8 Lymphocytes, CD8+ T Cell
Given IV
CyclophosphamideDrug
Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida
Given IV
LeukapheresisProcedure or surgery
Also called Leukocytopheresis, Therapeutic Leukopheresis
Undergo leukapheresis
UtomilumabBiological
Also called PF 05082566, PF 5082566, PF-05082566, PF-2566
Given IV

Study groups in NCT03318900
Study group	Role	What they receive
Treatment (T-cell infusion, aldesleukin, utomilumab)	Experimental	Patients undergo leukapheresis. Patients then receive cyclophosphamide IV on day -2, CD8-positive T-lymphocyte via infusion on day 0, and aldesleukin SC every 12 hours for 14 days. Beginning 24 hours after CD8-positive T-lymphocyte, patients also receive utomilumab IV over 90 minutes on days 1, 29, 57, 85, 113, and 141 in the absence of disease progression or unacceptable toxicity. Receives: Biological: Aldesleukin; Drug: CD8-Positive T-Lymphocyte; Drug: Cyclophosphamide; Procedure: Leukapheresis; Biological: Utomilumab

What is being measured

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

Assess Safety and Toxicity of Adoptively Transferred Central Memory-type CTL Targeting Ovarian Cancer Antigens Administered Alone, and in Combination With, Utomilumab, an Agonistic Anti-CD137 Antibody, in Patients With Platinum Resistant Ovarian Cancer
Due to lack of funding, the study was not able to accrue a sample size large enough to address the primary and secondary objectives
Measured: will continue to be monitored on study with visits every 8 weeks or as often as clinically indicated unless the disease gets worse, participants starts another therapy, or the participants are taken off study

Secondary outcomes (1)

Evaluate the Anti Tumor Effect of Adoptively Transferred Central Memory-type CTL Targeting Ovarian Cancer Antigens as Measured by Best Overall Response Rate (BORR) and Progression Free Survival (PFS).
Due to lack of funding, the study was not able to accrue a sample size large enough to address the primary and secondary objectives
Measured: will continue to be monitored on study with visits every 8 weeks or as often as clinically indicated unless the disease gets worse, participants starts another therapy, or the participants are taken off study

Timeline

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

4 Sep 201820 Dec 2023

First posted24 Oct 2017
Study start4 Sep 2018
Primary completion20 Dec 2023
Study completion20 Dec 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for COL6A3 PositiveStudies of the same condition, open and under way.
More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 5 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03318900
Sponsor's protocol ID: 2016-0400
Other IDs: NCI-2018-01034, 2016-0400
Status last verified: Oct 2024
First submitted: 16 Oct 2017
Last updated: 7 Nov 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Study at a glance

From the registry record, last updated by the sponsor on 7 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase I/Ib Study of Adoptive Cellular Therapy Using Autologous IL-21-Primed CD8+ Tumor Antigen-Specific T Cells in Combination With Utomilumab (PF-05082566) in Patients With Platinum Resistant Ovarian Cancer
ClinicalTrials.gov ID: NCT03318900
Acronym / sponsor ID: 2016-0400
Conditions: COL6A3 Positive, HLA-A*0201 Positive Cells Present, PRAME Positive, Recurrent Ovarian Carcinoma
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 5 participants (actual)
Lead sponsor: M.D. Anderson Cancer CenterUniversity, hospital or other
Collaborators: National Cancer Institute (NCI)
Study start: 4 Sep 2018 (actual)
Primary completion: 20 Dec 2023 (actual)
Study completion: 20 Dec 2023 (actual)
First posted: 24 Oct 2017 (actual)
Results: Posted 7 Nov 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

PRIMARY OBJECTIVES:

Assess the safety and toxicity of adoptively transferred central memory-type CTL targeting ovarian cancer antigens administered alone, and in combination with, utomilumab, an agonistic anti-CD137 antibody, in patients with platinum-resistant ovarian cancer.

II. Evaluate the functional and numeric in vivo persistence of adoptively transferred central memory-type CTL with and without utomilumab.

SECONDARY OBJECTIVES:

Evaluate the anti tumor effect of adoptively transferred central memory-type CTL targeting ovarian cancer antigens as measured by best overall response rate (BORR) and progression free survival (PFS).

OUTLINE: This is a dose escalation study of utomilumab.

After completion of study treatment, patients are followed up at days 3, 7, 14, 22, 28, 35, 43, 49, 56, 64, 70, 77, 84, 112, and 140.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Treatment (T-cell infusion, aldesleukin, utomilumab)	Experimental	Biological: Aldesleukin, Drug: CD8-Positive T-Lymphocyte, Drug: Cyclophosphamide, Procedure: Leukapheresis, Biological: UtomilumabPatients undergo leukapheresis. Patients then receive cyclophosphamide IV on day -2, CD8-positive T-lymphocyte via infusion on day 0, and aldesleukin SC every 12 hours for 14 days. Beginning 24 hours after CD8-positive T-lymphocyte, patients also receive utomilumab IV over 90 minutes on days 1, 29, 57, 85, 113, and 141 in the absence of disease progression or unacceptable toxicity.

Who may qualify

Ages: 18 to 75 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (19 listed)

Histopathologic documentation (must be performed or reviewed at MD Anderson) of recurrent high grade epithelial ovarian cancer.
At least one prior line of platinum-based chemotherapy (subjects are eligible for enrollment and leukapheresis while still platinum-sensitive, however, they must have developed platinum resistant disease for treatment (turnstile 2).
Tumor expressing PRAME and/or COL6A3.
Expression of HLA-A*0201.
Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

Key exclusion criteria (14 listed)

Clinically significant pulmonary dysfunction, as determined by medical history and physical exam. Patients so identified will undergo pulmonary functions testing and those with forced expiratory volume in one second (FEV1) < 60% of normal or carbon monoxide diffusing capacity (DLco) (corrected [corr] for hemoglobin [Hgb]) < 55% will be excluded.
Significant cardiovascular abnormalities including any one of the following: Congestive heart failure, Clinically significant hypotension, symptoms of coronary artery disease, presence of cardiac arrhythmias on electrocardiography (EKG) requiring drug therapy; or patients with a history of cardiovascular disease. (Patients with the above will undergo a cardiac evaluation which can include a stress test and/or echocardiography. Results of this evaluation will be considered before excluding patients on the basis of cardiovascular abnormalities). Subjects with evidence of stress-induced cardiac ischemia or ejection fraction less than 55% will be excluded.
History of central nervous system (CNS) metastasis.
Autoimmune disease: patients with a history of inflammatory bowel disease are excluded from this study, as are patients with a history of autoimmune disease (e.g. systemic lupus erythematosus, vasculitis, infiltrating lung disease) whose possible progression during treatment would be considered by the Investigator to be unacceptable.
{Turnstile 2} Participation in another clinical study with an investigational product administered during the last 28 days.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
AldesleukinAlso: 125-L-Serine-2-133-interleukin 2, Proleukin, r-serHuIL-2, Recombinant Human IL-2Given IV	Biological	Treatment (T-cell infusion, aldesleukin, utomilumab)
CD8-Positive T-LymphocyteAlso: CD8 Cell, CD8 Lymphocyte, CD8 Lymphocytes, CD8+ T CellGiven IV	Drug	Treatment (T-cell infusion, aldesleukin, utomilumab)
CyclophosphamideAlso: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, CiclofosfamidaGiven IV	Drug	Treatment (T-cell infusion, aldesleukin, utomilumab)
LeukapheresisAlso: Leukocytopheresis, Therapeutic LeukopheresisUndergo leukapheresis	Procedure or surgery	Treatment (T-cell infusion, aldesleukin, utomilumab)
UtomilumabAlso: PF 05082566, PF 5082566, PF-05082566, PF-2566Given IV	Biological	Treatment (T-cell infusion, aldesleukin, utomilumab)

Primary outcome

Assess Safety and Toxicity of Adoptively Transferred Central Memory-type CTL Targeting Ovarian Cancer Antigens Administered Alone, and in Combination With, Utomilumab, an Agonistic Anti-CD137 Antibody, in Patients With Platinum Resistant Ovarian Cancer
Time frame: will continue to be monitored on study with visits every 8 weeks or as often as clinically indicated unless the disease gets worse, participants starts another therapy, or the participants are taken off study
Due to lack of funding, the study was not able to accrue a sample size large enough to address the primary and secondary objectives

1 secondary outcome

Evaluate the Anti Tumor Effect of Adoptively Transferred Central Memory-type CTL Targeting Ovarian Cancer Antigens as Measured by Best Overall Response Rate (BORR) and Progression Free Survival (PFS).
Time frame: will continue to be monitored on study with visits every 8 weeks or as often as clinically indicated unless the disease gets worse, participants starts another therapy, or the participants are taken off study

Results and safety

Results posted to the registry on 7 Nov 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Dose Level 1	3	3
Dose Level 2	2	2
Dose Level 3	0	0

Primary outcome: Assess Safety and Toxicity of Adoptively Transferred Central Memory-type CTL Targeting Ovarian Cancer Antigens Administered Alone, and in Combination With, Utomilumab, an Agonistic Anti-CD137 Antibody, in Patients With Platinum Resistant Ovarian Cancer

Time frame: will continue to be monitored on study with visits every 8 weeks or as often as clinically indicated unless the disease gets worse, participants starts another therapy, or the participants are taken off study

Population analysed: Data were not collected due to lack of funding; the study was not able to accrue a sample size large enough to address the primary and secondary objectives

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Through study completion, an average of 18 months. Other adverse events reported at 1% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Dose Level 1	1 of 3 (33.3%)	3 of 3 (100%)	0 of 3
Dose Level 2	0 of 2 (0%)	2 of 2 (100%)	0 of 2
Dose Level 3	0 of 0	0 of 0	0

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Nov 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
M D Anderson Cancer CenterLink provided by the sponsor.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Amir A Jazaeri principal investigator

M.D. Anderson Cancer Center

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 14 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: finished, as of the sponsor's last update on 7 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Nov 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Assess Safety and Toxicity of Adoptively Transferred Central Memory-type CTL Targeting Ovarian Cancer Antigens Administered Alone, and in Combination With, Utomilumab, an Agonistic Anti-CD137 Antibody, in Patients With Platinum Resistant Ovarian Cancer (time frame: will continue to be monitored on study with visits every 8 weeks or as often as clinically indicated unless the disease gets worse, participants starts another therapy, or the participants are taken off study). 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 NCT03318900.

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 7 Nov 2024.