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Recurrent B-Cell Non-Hodgkin LymphomaPhase 1NCT04995536

CpG-STAT3 siRNA CAS3/SS3 and Localized Radiation Therapy for the Treatment of Relapsed/Refractory B-Cell NHL

A Phase 1 study testing CpG-STAT3 siRNA CAS3/SS3 and Radiation Therapy in people with Recurrent B-Cell Non-Hodgkin Lymphoma and Recurrent Diffuse Large B-Cell Lymphoma, run by City of Hope Medical Center.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This phase I trial identifies the best dose and side effects of CpG-STAT3 siRNA CAS3/SS3 (CAS3/SS3) in combination with localized radiation therapy in treating patients with B-cell non-Hodgkin lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
CpG-STAT3 siRNA CAS3/SS3 and Radiation Therapy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
27 Jul 2021to 4 Jan 2024
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

  • All subjects must have the ability to understand and the willingness to sign a written informed consent
  • Age 18 and older
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (corresponds to Karnofsky Performance Status [KPS] of >= 70)
  • Life expectancy greater than 16 weeks
  • Relapsed/refractory disease; patients must have failed >= 2 prior systemic therapies and have no treatment options known to provide clinical benefit
  • Biopsy confirmed relapsed or refractory B-cell lymphoma of the following subtypes; patients with a partial response to a previous treatment are allowed.
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  • Follicular grade 1 or 2, or 3 marginal zone or small lymphocytic lymphoma
  • Diffuse large B-cell lymphoma, non-germinal center B-cell like (GCB) type determined by immunohistochemistry using Han's algorithm
  • Mantle cell lymphoma
  • Patients must have at least two separate tumor sites, one of which is at least 2 cm in diameter and peripherally accessible and amenable for intratumoral injection of CAS3/SS3 with stabilization by palpation, and the other is at least 1.5 cm in diameter
  • Tumor specimens must be available for immunological studies either from a previous biopsy or a new biopsy obtained before the initiation of the study. Paraffin-embedded specimens are acceptable
  • Required wash out periods for prior therapy:
  • Topical therapy: 2 weeks
  • Chemotherapy: 4 weeks
  • Radiotherapy: 4 weeks
  • Other investigational therapy: 4 weeks
  • Monoclonal antibody or immunotherapy: 4 weeks
  • Targeted therapies: 4 weeks
  • Allogeneic transplant: 6 months
  • Absolute neutrophil count (ANC) >= 1,000/mm^3
  • NOTE: Growth factor is not permitted within 14 days of ANC assessment unless cytopenia is secondary to disease involvement
  • Platelets >= 75,000/mm^3
  • NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment unless cytopenia is secondary to disease involvement
  • Hemoglobin >= 8 g/dl
  • Total serum bilirubin (mg/dL): =< 1.5 x upper normal limit (ULN)
  • Aspartate aminotransferase (AST) < 3 x ULN without liver metastasis and < 5 x ULN with liver metastasis
  • Alanine aminotransferase (ALT) < 3 x ULN without liver metastasis and < 5 x ULN with liver metastasis
  • Adequate renal function as determined by serum creatinine =< 2.0 mg/dL or creatinine clearance of >= 50 mL/min per the Cockcroft-Gault formula
  • International normalized ratio (INR) OR prothrombin (PT) =< 1.5 x ULN
  • Activated partial thromboplastin time (aPTT) =< 1.5 x ULN
  • Female of childbearing potential: serum pregnancy test
  • Cardiac function 12-lead electrocardiogram (ECG) to confirm the absence of clinically significant arrhythmias
  • Left ventricular ejection fraction (LVEF) >= 45%
  • Oxygen saturation on room air of >= 92%
  • The effects of CAS3/SS3 on the developing fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation. Should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately

Who cannot join

  • Patients may not be receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy
  • Current use of anticoagulant therapy (aspirin [ASA] =< 325 mg per day allowed) or history of significant bleeding diathesis
  • Treatment with corticosteroids or other systemic immunosuppressive medication (e.g., methotrexate, rapamycin) within 28 days of study treatment. Note: patients with adrenal insufficiency may take up to 7.5 mg of prednisone or equivalent daily. Topical and inhaled corticosteroids in standard doses are allowed
  • Patients with rapid progression of disease requiring immediate anti lymphoma therapy
  • Patients should not have any uncontrolled illness including ongoing or active infection
  • Pregnant or lactating women are excluded from this study because CAS3/SS3is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with CAS3/SS3, breastfeeding should be discontinued if the mother is treated with CAS3/SS3
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  • Prior malignancy (active within 5 years of screening) except basal cell or completely excised non-invasive squamous cell carcinoma of the skin, or in situ squamous cell carcinoma of the cervix
  • Pre-existing autoimmune or antibody mediated disease including: systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome, autoimmune thrombocytopenia, Addison's disease, but excluding the presence of autoantibodies without clinical autoimmune disease
  • History of inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis), celiac disease, or other chronic gastrointestinal conditions associated with diarrhea, or current acute colitis of any origin
  • History of diverticulitis (even a single episode) or evidence of diverticulitis at baseline, including evidence limited to computed tomography (CT) scan only. Note: diverticulosis is not an exclusion criterion per se
  • Graft versus host disease
  • Severe psoriasis
  • Active thyroiditis
  • History of uveitis
  • Known history of human immunodeficiency virus (HIV) with detectable viral load or patients with acquired immuno-deficiency syndrome (AIDS) are excluded
  • Known active or chronic viral hepatitis B or C infection
  • Patients with active infection or with a fever > 38.5 degrees Celsius (C) within three days prior to the first scheduled treatment
  • Active central nervous system (CNS) metastases
  • History of allergic reactions attributed to compounds of similar composition to agatolimod sodium (PF-3512676) or tremelimumab
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to CAS3/SS3
  • Significant cardiovascular disease (i.e. New York Heart Association [NYHA] >= class 3 congestive heart failure; myocardial infarction within the past 6 months; unstable angina; coronary angioplasty within the past 6 months; uncontrolled atrial or ventricular cardiac arrhythmias)
  • Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
  • Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

About this study

Official title: A Phase I Study of Intratumoral Injections of CpG-STAT3 siRNA (CAS3/SS3) in Combination With Local Radiation in Patients With Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma (NHL)

This phase I trial identifies the best dose and side effects of CpG-STAT3 siRNA CAS3/SS3 (CAS3/SS3) in combination with localized radiation therapy in treating patients with B-cell non-Hodgkin lymphoma that has come back (relapsed) or does not respond to treatment (refractory). CAS3/SS3 simultaneously targets two molecules, TLR9 receptor and STAT3. This investigational drug combines a CpG oligonucleotide and an siRNA in one molecule that act together to interfere with the ability of the cancer cells to grow. Radiation therapy uses high energy x-rays to kill cancer cells and shrink tumors. Giving CAS3/SS3 with localized radiation therapy may kill more cancer cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine the recommended phase 2 dose (RP2D) of CAS3/SS3 when given in combination with local fixed-dose radiation therapy (RT).

II. Evaluate the safety and feasibility of intratumoral injections of CAS3/SS3 when combined with local fixed-dose RT, by evaluation of toxicities including: type, frequency, severity, attribution, time course and duration.

SECONDARY OBJECTIVES:

  1. Characterize the clinical activity (overall and per dose level) of CAS3/SS3 through the assessment of disease response, and response duration. (Clinical) II. Characterize the biologic activity (overall and per dose level) of CAS3/SS3 when combined with local fixed-dose RT by assessing. (Biologic [Immunologic Correlative Studies]) IIa. Silencing of the STAT3 gene and its key downstream genes. IIb. Local and systemic immune responses, including: evidence/extent of immune cell intratumoral infiltration, immune cell activation within the tumor and in the peripheral blood, and changes in proinflammatory mediators in plasma.

OUTLINE:

Patients undergo radiation therapy on days 1 and 2 tumor-bearing lymph node, and receive CAS3/SS3 intratumorally on days 2, 4, 16, and 18. Patients assigned to dose level 3 also receive CAS3/SS3 intratumorally on days 9, 11, 23, and 25.

After completion of study treatment, patients are followed up every 3 months.

Being tested
CpG-STAT3 siRNA CAS3/SS3, Radiation Therapy
Medical subject headings
Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular, Lymphoma, Mantle-Cell, Lymphoma, B-Cell, Marginal Zone, Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

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

  • CpG-STAT3 siRNA CAS3/SS3Biological

    Also called CAS3/SS3, CpG ODN/STAT3 siRNA CAS3/SS3, CpG Oligodeoxynucleotide/STAT3 siRNA CAS3/SS3, CpG/Anti-STAT3 siRNA CAS3/SS3

    Given intratumorally

  • Radiation TherapyRadiation

    Also called Cancer Radiotherapy, ENERGY_TYPE, Irradiate, Irradiated

    Undergo radiation therapy

Study groups in NCT04995536
Study groupRoleWhat they receive
Treatment (radiation therapy, CAS3/SS3)ExperimentalPatients undergo radiation therapy on days 1 and 2 tumor-bearing lymph node, and receive CAS3/SS3 intratumorally on days 2, 4, 16, and 18. Patients assigned to dose level 3 also receive CAS3/SS3 intratumorally on days 9, 11, 23, and 25.
Receives: Biological: CpG-STAT3 siRNA CAS3/SS3; Radiation: Radiation Therapy

What is being measured

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

  1. Incidence of adverse events

    Toxicity will be graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events version 5. Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, attribution, time of onset, duration, and reversibility or outcome.

    Measured: Up to 6 months

  2. Dose Limiting Toxicity

    Grade 3 or higher toxicities at least possibly related to study treatment as assessed by CTCAE, with noted exceptions.

    Measured: Up to 56 days

Secondary outcomes (5)

  1. Overall response

    Will be categorized using the 2014 Lugano response criteria for malignant lymphoma.

    Measured: From 56 days through 6 months

  2. Response duration

    Time interval from the date of first documented response (CR or PR) to documented disease relapse, progression or death whichever occurs first, assessed up to 2 years

    Measured: Up to 6 months

  3. Suppression of STAT3 expression

    Measurement of STAT3 mRNA cleavage in lymph node tissue and peripheral blood mononuclear cells using RACE

    Measured: up to 56 days

  4. Suppression of STAT3 activation of downstream targets.

    Suppression of STAT3 activation of downstream target genes and immune genes as assessed by Nanostring in lymph node tissue

    Measured: Up to 19 days

  5. Activation of immune cells

    Serum IFNs, IP-10, MCP1 levels will be evaluated as evidence for systemic effects of CAS3/SS3 injections.

    Measured: Up to 56 days

Timeline

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

  1. First posted9 Aug 2021
  2. Study start27 Jul 2021
  3. Primary completion4 Jan 2024
  4. Study completion4 Jan 2024

Why it stopped: no accrual

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
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04995536
Sponsor's protocol ID
20589
Other IDs
NCI-2021-06965, 20589, P30CA033572, P50CA107399, Scopus Biopharma
Status last verified
Apr 2024
First submitted
20 Jul 2021
Last updated
25 Apr 2024
Results posted
No
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 study testing CpG-STAT3 siRNA CAS3/SS3 and Radiation Therapy in people with Recurrent B-Cell Non-Hodgkin Lymphoma and Recurrent Diffuse Large B-Cell Lymphoma, run by City of Hope Medical Center.

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 35 inclusion and 23 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: withdrawn, as of the sponsor's last update on 25 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

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 withdrawn before enrolling participants, so there are no results.

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 adverse events (time frame: Up to 6 months). 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 NCT04995536.

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 25 Apr 2024.

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