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Aggressive Non-Hodgkin LymphomaPhase 1/2NCT03035331

Dendritic Cell Therapy, Cryosurgery, and Pembrolizumab in Treating Patients With Non-Hodgkin Lymphoma

A Phase 1/2 study testing Cryosurgery, Dendritic Cell Therapy and Laboratory Biomarker Analysis in people with Aggressive Non-Hodgkin Lymphoma and Indolent Non-Hodgkin Lymphoma, run by Mayo Clinic 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

This phase I/II trial studies the best dose and side effects of dendritic cell therapy, cryosurgery and pembrolizumab in treating patients with non-Hodgkin lymphoma. Vaccines, such as dendritic cell therapy made from a person's tumor cells and white blood cells may help the body build an effective immune response to… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cryosurgery, Dendritic Cell Therapy and Laboratory Biomarker Analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
1 siteUnited States
Study dates
15 Aug 2017to 10 Sep 2022
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age >= 18 years
  • Histological confirmation of biopsy-proven non-Hodgkin lymphoma, excluding chronic lymphocytic leukemia, primary central nervous system (CNS) lymphoma and Burkitt's lymphoma; Note: small lymphocytic lymphoma (SLL) is allowed
  • Patients with indolent non-Hodgkin lymphoma (NHL) must have had >= 1 regimen of rituximab-containing regimen; Note: this includes follicular lymphoma (FL), marginal lymphoma and mucosa-associated lymphoid tissue (MALT)
  • Patients with aggressive NHL must have had >= 2 regimens; Note: This includes diffuse large B cell lymphoma (DLBCL), mantle cell lymphoma (MCL), primary mediastinal large B-cell lymphoma (PMBCL), and T cell lymphoma
  • Patient with aggressive NHL must have received prior therapy - at a minimum:
  • Anti-CD20 monoclonal antibody unless tumor is CD20 negative and
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  • An anthracycline containing regimen
  • Transformed FL must have had therapy for FL and be refractory to chemotherapy for DLBCL
  • Chemotherapy refractory disease in aggressive NHL is defined as
  • Stable disease of =< 12 months or progressive disease as best response to most recent chemotherapy containing regimen
  • Disease progression or recurrence =< 12 months of prior autologous stem cell transplantation (SCT)
  • Patients with aggressive NHL must have failed autologous hematopoietic stem cell transplantation (HSCT), or are ineligible or not consenting to autologous HSCT
  • Patient must have at least 3 measurable lesions that are >= 1.5 cm in one dimension; one of the lesions must be >= 2.0 cm and is amenable to image-guided cryoablation and multiple vaccine injections as determined by interventional radiology and principal investigator (PI) (including tumors that can be safely accessed using imaging guidance and treated with minimal risk to adjacent structures)
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
  • Absolute neutrophil count (ANC) >= 1000/mm^3 (obtained =< 14 days prior to registration)
  • Absolute lymphocyte count >= 200/mm^3 (obtained =< 14 days prior to registration)
  • Platelet count >= 50,000/mm^3 (obtained =< 14 days prior to registration)
  • Hemoglobin >= 8.0 g/dL (obtained =< 14 days prior to registration)
  • Total bilirubin =< 1.5 x upper limit of normal (ULN), unless due to Gilbert's disease (obtained =< 14 days prior to registration)
  • Aspartate transaminase (AST/serum glutamic-oxaloacetic transaminase [SGOT]) and alanine transaminase (ALT/serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN (obtained =< 14 days prior to registration)
  • Creatinine =< 1.5 x ULN or calculated creatinine clearance >= 60 mL/min for subject with creatinine ˃ 1.5 x institutional ULN (obtained =< 14 days prior to registration)
  • Negative serum pregnancy test for women of childbearing potential =< 7 days prior to registration; Note: a second pregnancy test may be required =< 72 hours prior to receiving the first dose of study medication
  • Negative human immunodeficiency virus (HIV), hepatitis B and C, and tuberculosis (TB) test
  • Provide written informed consent
  • Willing to return to the enrolling institution for follow-up (during active treatment and active monitoring phase of the study)
  • Ability to complete questionnaire(s) by themselves or with assistance
  • Willing to provide tissue and blood samples for research purposes
  • Willing to use adequate contraception while on the study and until 120 days after the last dose of study drug

Who cannot join

  • Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
  • Pregnant women
  • Nursing women
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Serious non-malignant disease such as active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations or other conditions which in the opinion of the investigator would compromise protocol objectives
  • Currently receiving or have received any other investigational agent considered as a treatment for the primary neoplasm =< 28 days or within 4 half-lives (whichever is shorter) of the agent prior to registration
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  • History of other primary malignancy requiring systemic treatment within 6 months of protocol enrollment; patients must not be receiving chemotherapy or immunotherapy for another cancer; patients must not have another active malignancy requiring active treatment with the following acceptable EXCEPTIONS:
  • Basal cell carcinoma, squamous cell carcinoma, or melanoma of the skin that has undergone or will undergo potentially curative therapy
  • In situ cervical cancer that has undergone or will undergo potentially curative therapy
  • Prior allogeneic bone marrow or peripheral blood stem cell transplantation
  • Prior autologous bone marrow or peripheral blood stem cell transplantation =< 100 days prior to registration or if recovery from the transplant is inadequate
  • Major surgery other than diagnostic surgery =< 4 weeks prior to registration
  • Prior chemotherapy or radiation therapy =< 2 weeks prior to registration or who has not recovered (i.e. to =< grade 1 or baseline) from an adverse event due to the previously administered therapy
  • History of hypersensitivity and anaphylactoid reactions to pneumococcal vaccine or any component of the formulation, including diphtheria toxoid
  • Active autoimmune disease such as Crohn's disease, rheumatoid arthritis, Sjogren's disease, systemic lupus erythematosus, or similar conditions requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease/syndrome difficult to control in the past
  • EXCEPTIONS:
  • Vitiligo or resolved childhood asthma/atopy
  • Intermittent use of bronchodilators or local steroid injections
  • Hypothyroidism stable on hormone replacement,
  • Diabetes stable with current management
  • History of positive Coombs test but no evidence of hemolysis
  • Psoriasis not requiring systemic treatment
  • Conditions not expected to recur in the absence of an external trigger
  • Coagulopathy, including the use of Coumadin or heparin anticoagulants that cannot be discontinued for the cryoablation procedure; NOTE: heparin for line patency without detectable lab abnormalities for coagulation will be allowed
  • Corticosteroid use =< 2 weeks prior to registration; NOTE: patients must be off corticosteroids for at least 2 weeks prior to registration; this includes oral, IV, subcutaneous, or inhaled route of administration; patients on chronic corticosteroid for adrenal insufficiency or other reasons may enroll if they receive less than 10 mg/day of prednisone (or equivalent)
  • Active CNS malignancy
  • Evidence of interstitial lung disease or active, non-infectious pneumonitis
  • Received a live vaccine =< 30 days prior to registration
  • New York Heart Association classification III or IV cardiovascular disease or recent myocardial infarction or unstable angina pectoris or cardiac arrhythmia =< 30 days prior to registration

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: Phase I/II Study of Dendritic Cell Therapy Delivered Intratumorally After Cryoablation and Anti-PD-1 Antibody (Pembrolizumab) for Patients With Non-Hodgkin Lymphoma

This phase I/II trial studies the best dose and side effects of dendritic cell therapy, cryosurgery and pembrolizumab in treating patients with non-Hodgkin lymphoma. Vaccines, such as dendritic cell therapy made from a person's tumor cells and white blood cells may help the body build an effective immune response to kill tumor cells. Cryosurgery kills cancer cells by freezing them. 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 dendritic cell therapy, cryosurgery and pembrolizumab may work better at treating non-Hodgkin lymphoma.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Evaluate the optimal dose schedule, safety and tolerability as measured by the incidence of significant toxicity of combination therapy with anti-PD-1 monoclonal antibody, cryoablation, and intra-tumor injection of autologous dendritic cell into the cryoablated tumor. (Phase I) II. Test the efficacy (overall response rate) of combination therapy with anti-PD-1 monoclonal antibody, cryoablation, and intra-tumor injection of autologous dendritic cell vaccine. (Phase II)

SECONDARY OBJECTIVES:

  1. Evaluate the feasibility of this combination immunotherapy. (Phase I) II. Evaluate patient quality of life. (Phase I) III. Evaluate the partial response (PR) and complete response (CR) rate of this combination immunotherapy. (Phase II) IV. Evaluate the progression free survival, treatment free survival, duration of response, disease-free rate at 2 years, and overall survival of this combination immunotherapy. (Phase II) V. Evaluate the safety of this combination immunotherapy. (Phase II)

CORRELATIVE OBJECTIVES:

  1. Assess the effect of combination immunotherapy on patients' immune status and anti-tumor immune response. (Phase II) II. Assess the potential association between PD-1/PD-L1/PD-L2 expression in tumor and blood with clinical efficacy. (Phase II) III. Assess the potential association between tumor antigen mutations and antigen-specific immune response with clinical efficacy. (Phase II) IV. Evaluate patient quality of life. (Phase II)

OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

Patients receive pembrolizumab intravenously (IV) on day 1. Treatment repeats every 21 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive dendritic cell therapy intratumorally (IT) on days 2, 8, and 15 of cycles 2 and 3, and day 2 of cycles 4 and 5. Patients undergo cryosurgery on day 2 of cycle 2 and receive pneumococcal 13-valent conjugate vaccine by injection on day 2 of cycles 2-5. Treatment repeats every 21 days for up to 5 cycles in the absence of disease progression or unacceptable toxicity. Patients who are CR, PR, or stable disease (SD) after completion of therapy, may receive pembrolizumab for an additional 18 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months during the first year post-treatment, every 4 months during the second year post-treatment, and then every 6 months for up to 2 years.

Being tested
Cryosurgery, Dendritic Cell Therapy, Laboratory Biomarker Analysis, Pembrolizumab, Pneumococcal 13-valent Conjugate Vaccine
Medical subject headings
Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular, Lymphoma, Mantle-Cell, Lymphoma, B-Cell, Marginal Zone, Lymphoma, Non-Hodgkin, Lymphoma, T-Cell, Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

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

  • CryosurgeryProcedure or surgery

    Also called Ablation, Cryo, Cryoablation, cryosurgical ablation

    Undergo cryosurgery

  • Dendritic Cell TherapyBiological

    Also called Dendritic Cell Vaccine Therapy

    Given IT

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • PembrolizumabBiological

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

    Given IV

  • Pneumococcal 13-valent Conjugate VaccineBiological

    Also called PCV 13, PCV13 Vaccine, Prevnar 13

    Given by injection

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

Study groups in NCT03035331
Study groupRoleWhat they receive
Treatment (pembrolizumab, dendritic cell therapy, cryosurgery)ExperimentalPatients receive pembrolizumab IV on day 1. Treatment repeats every 21 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive dendritic cell therapy IT on days 2, 8, and 15 of cycles 2 and 3, and day 2 of cycles 4 and 5. Patients undergo cryosurgery on day 2 of cycle 2 and receive pneumococcal 13-valent conjugate vaccine by injection on day 2 of cycles 2-5. Treatment repeats every 21 days for up to 5 cycles in the absence of disease progression or unacceptable toxicity. Patients who are CR, PR, or SD after completion of therapy, may receive pembrolizumab for an additional 18 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Procedure: Cryosurgery; Biological: Dendritic Cell Therapy; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Biological: Pneumococcal 13-valent Conjugate Vaccine; Other: Quality-of-Life Assessment

What is being measured

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

  1. Number of Patients That Experienced a Dose Limiting Toxicity (DLT)

    Maximum tolerated dose (MTD) will be defined as the dose level that does not induce dose limiting toxicity in at least one-third of patients. DLTs are defined as Grade 4 or 5 ANC or PLT for at least 7 days, grade 3 plus Infections and infestations, febrile neutropenia defined as fever ≥38.5oC (38 >1 hour) with grade 4 plus neutropenia, at least Grade 3 erythema multiforme, ulceration, or urticaria that does not resolve to Grade 2 or less within > three weeks, at least grade 3 bronchial obstruction, pneumonitis, or wheezing at least grade 3 allergic reaction or autoimmunity at least grade 3 that does not resolve to less than Grade 2> less than or equal to 72 hours per NCI Common Terminology Criteria for Adverse Events.

    Measured: 56 days

  2. Percentage of Complete Responses of Combination Therapy With Pembrolizumab, Cryoablation, and Intra-tumor Injection of Autologous Dendritic Cells (DC) at Maximum Tolerated Dose (MTD) Dose

    The percentage of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated.

    Measured: 24 months

Secondary outcomes (7)

  1. Progression Free Survival

    The distribution of survival time will be estimated using the method of Kaplan-Meier.

    Measured: 24 months

  2. Treatment Free Survival

    The distribution of treatment-free survival will be estimated using the method of Kaplan-Meier.

    Measured: 34 months

  3. Duration of Response

    The distribution of duration of complete response will be estimated using the method of Kaplan-Meier.

    Measured: 11 months

  4. Disease Free Survival Rate

    The percentage of patients without disease at two years post start of treatment.

    Measured: 2 years

  5. Overall Survival

    The distribution of survival time will be estimated using the method of Kaplan-Meier.

    Measured: 5 years

  6. Percentage of Patients With Grade 4 or 5 Adverse Events

    Will be assessed by Common Terminology Criteria for Adverse Events version 4.0.

    Measured: Up to 4 years

  7. Percent of Patients With Improved Quality of Life

    Will be measured using the Functional Assessment of Cancer Therapy-lymphoma. The assessment will be scored according to the scoring algorithm. Changes from baseline will be calculated at each assessment time points. Mean change scores at each time point will be calculated to determine if quality of life is reduced over the course of treatment. Longitudinal techniques will be employed to describe changes over time.

    Measured: 4 years

Timeline

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

  1. First posted30 Jan 2017 (estimated)
  2. Study start15 Aug 2017
  3. Primary completion25 Jan 2022
  4. Study completion10 Sep 2022

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03035331
Sponsor's protocol ID
MC1685
Other IDs
P50CA097274, 16-005856, R01CA219960
Status last verified
Dec 2024
First submitted
26 Jan 2017
Last updated
4 May 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Cryosurgery, Dendritic Cell Therapy and Laboratory Biomarker Analysis in people with Aggressive Non-Hodgkin Lymphoma and Indolent Non-Hodgkin Lymphoma, run by Mayo Clinic 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 28 inclusion and 29 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 4 May 2026. 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 16 May 2025). 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?

Number of Patients That Experienced a Dose Limiting Toxicity (DLT) (time frame: 56 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 NCT03035331.

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 4 May 2026.

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