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

NCT04995536 | Withdrawn Phase 1 DMC FDA Drug

• 5 other identifiers: 20589NCI-2021-06965P30CA033572P50CA107399Scopus Biopharma
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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). 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.

Conditions

Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Grade 3a Follicular Lymphoma; Recurrent Grade 3b Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Grade 1 Follicular Lymphoma; Refractory Grade 2 Follicular Lymphoma; Refractory Grade 3 Follicular Lymphoma; Refractory Grade 3a Follicular Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Marginal Zone Lymphoma; Refractory Small Lymphocytic Lymphoma; Refractory Grade 3b Follicular Lymphoma

Outcome Measures

Primary Outcomes (2)

• 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.

  Up to 6 months

• Dose Limiting Toxicity

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

  Up to 56 days

Secondary Outcomes (5)

• Overall response

  From 56 days through 6 months

• Response duration

  Up to 6 months

• Suppression of STAT3 expression

  up to 56 days

• Suppression of STAT3 activation of downstream targets.

  Up to 19 days

• Activation of immune cells

  Up to 56 days

Study Arms (1)

Treatment (radiation therapy, CAS3/SS3)

EXPERIMENTAL

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.

Biological: CpG-STAT3 siRNA CAS3/SS3; Radiation: Radiation Therapy

Interventions

CpG-STAT3 siRNA CAS3/SS3 BIOLOGICAL

Given intratumorally

Also known as: CAS3/SS3, CpG ODN/STAT3 siRNA CAS3/SS3, CpG Oligodeoxynucleotide/STAT3 siRNA CAS3/SS3, CpG/Anti-STAT3 siRNA CAS3/SS3, CpG/STAT3 siRNA CAS3/SS3, TLR9 Agonist/STAT3 siRNA Conjugate CAS3/SS3

Treatment (radiation therapy, CAS3/SS3)

Radiation Therapy RADIATION

Undergo radiation therapy

Also known as: Cancer Radiotherapy, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Treatment (radiation therapy, CAS3/SS3)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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
• 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
• 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

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Lymphoma, B-Cell, Marginal Zone; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

CPG-oligonucleotide; Radiotherapy; Radiation

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutics; Physical Phenomena

Study Officials

• Lihua E Budde

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2021
• First Posted: August 9, 2021
• Study Start: July 27, 2021
• Primary Completion: January 4, 2024
• Study Completion: January 4, 2024
• Last Updated: April 25, 2024

Record last verified: 2024-04