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Colorectal AdenocarcinomaPhase 1NCT02757391

CD8+ T Cell Therapy and Pembrolizumab in Treating Patients With Metastatic Gastrointestinal Tumors

A Phase 1 study testing Adoptive Immunotherapy, Aldesleukin and Cyclophosphamide in people with Colorectal Adenocarcinoma and Metastatic Cholangiocarcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This phase I pilot trial studies the side effects of cluster of differentiation 8 (CD8)+ T cells in treating patients with gastrointestinal tumors that have spread to other places in the body. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Adoptive Immunotherapy, Aldesleukin and Cyclophosphamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
1 siteUnited States
Study dates
9 Aug 2019to 2 Oct 2020
Phase
Phase 1
Are there results?
None posted in the registry

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histopathologic documentation of pancreatic adenocarcinoma, colorectal adenocarcinoma, cholangiocarcinoma, esophageal cancer and gastric cancer with radiographic evidence of metastatic disease.
  • Male or female subjects greater than or equal to 18 years of age.
  • ECOG/ Zubrod performance status of 0 or 1.
  • 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 at least 8 weeks after pembrolizumab is stopped. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal. Acceptable forms of birth control include condom, diaphragm, hormonal, IUD, or sponge plus spermacide. Abstinence is also an acceptable form of birth control.
  • Men must be willing and able to use an acceptable method of birth control, during and for at least 3 months after completion of the study, if their sexual partners are WOCBP.
  • Willing and able to give informed consent.
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  • Adequate vein access: consider PICC or other central line.
  • Patients must have adequate tissue (fresh or frozen) available or planned removal of adequate tissue for analysis. At least 250mg of tumor are needed for peptide elution. There is no specific time limit on how long the tissue can remain frozen prior to use. The tissue will be collected and analyzed under Lab protocol PA15-0176.
  • Patients can have any lines (including zero) of prior therapy to sign consent prior to tissue harvest.
  • Toxicity related to prior therapy must either have returned to </= grade 1, baseline, or been deemed irreversible.
  • ELIGIBILITY FOR TREATMENT: ECOG/Zubrod performance status of 0 to 2.
  • Bi-dimensionally measurable disease by radiographic imaging (CT scan) that represents at least one measurable lesion per RECIST v1.1.
  • At least 4 Weeks must have elapsed since the last chemotherapy, radiotherapy or major surgery.
  • Toxicity related to prior therapy must either have returned to less than or equal to grade 1, baseline, or been deemed irreversible.
  • Subjects must have received at least one line of chemotherapy prior to receiving adoptive T cell therapy and should have exhausted standard of care systemic therapy options. The decision to implement the T cell therapy will be at the discretion of the treating physician. The timing and total exposure to chemotherapy will depend on the tumor type in question (more systemic options for breast cancer; fewer for gastric cancer, for example). Due to the heterogeneity of tumors being treated in this protocol, the discretion of the treating physician in terms of timing of immunotherapy will be critical.

Who cannot join

  • EXCLUSION FOR ENROLLMENT: Any other malignancy from which the patient has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer, and carcinoma in situ of the cervix.
  • Pregnant women, nursing mothers, men or women of reproductive ability who are unwilling to use effective contraception. Women of childbearing potential with a positive pregnancy test within 3 days prior to entry.
  • Significant cardiovascular abnormalities as defined by any one of the following: 1. Congestive heart failure NYHA classes II-IV. Patients with asymptomatic class I CHF may participate in conjunction with a Cardiology consultation. 2. Clinically significant hypotension. 3. Symptoms of coronary artery disease. 4. Presence of arrhythmias in EKG requiring drug therapy.
  • Active and untreated central nervous system (CNS) metastases (including metastasis identified during screening MRI or contrast CT). Patients with asymptomatic, treated metastases may be eligible if their lesion(s) have demonstrated stability over 2 months.
  • 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.
  • 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, such as a condition associated with frequent diarrhea.
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  • Inadequate organ function at enrollment defined by: WBC less than or equal to 2000/uL. Hct less than or equal to 24% or Hgb less than or equal to 8 g/dL. ANC less than or equal to 1000. Platelets less than or equal to 75,000. Creatinine greater than or equal to 1.5 x ULN OR creatinine clearance >50 ml/min/1.73m2 for patients with creatinine levels above institutional normal limits. AST/ALT greater than or equal to 2.5 x ULN. Bilirubin greater than or equal to 2.0 x ULN
  • Positive screening tests for HIV, Hep B, and Hep C. If positive results are not indicative of true active or chronic infection, the patient can be treated
  • EXCLUSION CRITERIA FOR TREATMENT: WBC less than or equal to 2000/uL. Hct less than or equal to 24% or Hgb less than or equal to 8 g/dL. ANC less than or equal to 1000. Platelets less than or equal to 75,000. Creatinine greater than or equal to 1.5 x ULN OR creatinine clearance >50 ml/min/1.73m2 for patients with creatinine levels above institutional normal limits. AST/ALT greater than or equal to 2.5 x ULN. Bilirubin greater than or equal to 2.0 x ULN
  • Pregnant women, nursing mothers, men or women of reproductive ability who are unwilling to use effective contraception. Women of childbearing potential with a positive pregnancy test within 3 days prior to entry.
  • Steroids are not permitted 3 days prior to T cell infusion and concurrently during therapy.
  • Uncontrolled concurrent 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.
  • Any non-oncology vaccine therapy used for the prevention of infectious disease within 1 month before or after any anti-PD-1 dose.
  • After the T cell infusion, patients may not be on any other treatments for their cancer aside from those included in the treatment section of the protocol.
  • Coagulation ≤1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or a PTT is within therapeutic range of intended use of anticoagulants.

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: Pilot Study of Feasibility and Safety of Personalized Autologous CD8+ T Cell Therapy Plus Anti-PD1 Antibody in Advanced Solid Malignancies

This phase I pilot trial studies the side effects of cluster of differentiation 8 (CD8)+ T cells in treating patients with gastrointestinal tumors that have spread to other places in the body. Tumor cells and blood are used to help create an adoptive T cell therapy, such as CD8+ T cell therapy, that is individually designed for a patient and may help doctors learn more about genetic changes in the tumor. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving CD8+ T cell therapy and pembrolizumab may work better in treating patients with gastrointestinal tumors.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Assess the safety of using a personalized adoptive T cell therapy in patients with advanced gastrointestinal malignancies.

SECONDARY OBJECTIVES:

  1. Assess the persistence of an immune response after T cell infusion. II. Determine the clinical benefit of adoptive T cell therapy in advanced gastrointestinal cancers.

OUTLINE:

Beginning 2 days prior to CD8+ T cell infusion, patients receive cyclophosphamide intravenously (IV) over 30 minutes. Patients undergo CD8+ T cell infusion IV over 2 hours on day 0 and receive aldesleukin subcutaneously (SC) twice daily (BID) on days 1-14. Beginning on day 1 about 24 hours after CD8+ T cell infusion, patients receive pembrolizumab IV over 30-60 minutes on weeks 3, 6, 12, and 15.

After completion of study treatment, patients are followed up for 24 weeks.

Being tested
Adoptive Immunotherapy, Aldesleukin, Cyclophosphamide, Laboratory Biomarker Analysis, Pembrolizumab
Medical subject headings
Cholangiocarcinoma, Colorectal Neoplasms, Esophageal Neoplasms, Stomach Neoplasms

What participants receive

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

  • Adoptive ImmunotherapyBiological

    Also called ACT, ACT Therapy, Adoptive Cell Immunotherapy, Adoptive Cell Transfer

    Undergo CD8 +T cell therapy

  • AldesleukinBiological

    Also called 125-L-Serine-2-133-interleukin 2, Proleukin, r-serHuIL-2, Recombinant Human IL-2

    Given SC

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • PembrolizumabBiological

    Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475

    Given IV

Study groups in NCT02757391
Study groupRoleWhat they receive
Treatment (CD8 +T cell therapy, pembrolizumab)ExperimentalBeginning 2 days prior to CD8+ T cell infusion, patients receive cyclophosphamide IV over 30 minutes. Patients undergo CD8+ T cell infusion IV over 2 hours on day 0 and receive aldesleukin SC BID on days 1-14. Beginning on day 1 about 24 hours after CD8+ T cell infusion, patients receive pembrolizumab IV over 30-60 minutes on weeks 3, 6, 12, and 15.
Receives: Biological: Adoptive Immunotherapy; Biological: Aldesleukin; Drug: Cyclophosphamide; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab

What is being measured

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

  1. Incidence of toxicity defined as grade 3 or 4 non-hematologic or grade 4 hematologic toxicity per Common Terminology Criteria for Adverse Events version 4.0

    Will monitor toxicity of the personalized vaccines in using cohorts of size of 5, starting from the 1st patient using the Bayesian approach of Thall, Simon, Estey.

    Measured: Up to 24 weeks

Secondary outcomes (8)

  1. Persistence of an immune response defined by level of tetramer positive T cell population over time after T cell infusion

    Measured: Up to 24 weeks

  2. Persistence of an immune response defined by T cell interferon gamma release in response to selected personalized peptide antigens

    Measured: Up to 24 weeks

  3. Persistence of an immune response defined by levels of intracellular cytokine staining of T cells in response to stimulation with personalized peptide antigens

    Measured: Up to 24 weeks

  4. Persistence of an immune response defined by detection of antigen spreading

    Measured: Up to 24 weeks

  5. Proportion of patients who have received T cell infusion that is alive and progression free (complete response [CR] + partial response [PR] + stable disease) defined based on response criteria according to Response Evaluation Criteria in Solid Tumors 1.1

    Measured: At 12 weeks post infusion

  6. Time to progression

    Measured: Up to 24 weeks

  7. Response rate (CR + PR)

    The response rate will be evaluated using a Simon optimal two-stage design.

    Measured: Up to 24 weeks

  8. Overall survival

    Measured: Up to 24 weeks

Timeline

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

  1. First posted2 May 2016 (estimated)
  2. Study start9 Aug 2019
  3. Primary completion2 Oct 2020
  4. Study completion2 Oct 2020

Why it stopped: Study halted prematurely and will not resume; participants are no longer being examined or receiving intervention.

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02757391
Sponsor's protocol ID
2015-0152
Other IDs
NCI-2016-01058, 2015-0152
Status last verified
Oct 2020
First submitted
26 Apr 2016
Last updated
30 Oct 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Adoptive Immunotherapy, Aldesleukin and Cyclophosphamide in people with Colorectal Adenocarcinoma and Metastatic Cholangiocarcinoma, run by M.D. Anderson Cancer Center at 1 site 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 15 inclusion and 15 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: stopped early, as of the sponsor's last update on 30 Oct 2020. 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 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?

The study was stopped early (reason given: Study halted prematurely and will not resume; participants are no longer being examined or receiving intervention.). Results are not available in the source record.

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?

Incidence of toxicity defined as grade 3 or 4 non-hematologic or grade 4 hematologic toxicity per Common Terminology Criteria for Adverse Events version 4.0 (time frame: Up to 24 weeks). 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 NCT02757391.

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 30 Oct 2020.

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