Study of SD-101 in Combination With Localized Low-dose Radiation in Patients With Untreated Low-grade B-cell Lymphoma

NCT02266147 | Terminated Phase 1 Results

• 1 other identifier: DV3-LYM-01
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 5

Brief Summary

To assess the safety and tolerability of escalating doses of SD-101 in combination with localized low-dose radiation therapy in adult subjects with untreated low-grade B-cell lymphoma.

Conditions

B-cell Lymphoma

Keywords

Low Grade B-cell Lymphoma

Outcome Measures

Primary Outcomes (4)

• Number of Participants Experiencing Dose-limiting Toxicities (DLTs) and Maximum Tolerated Dose (MTD).

  Up to Day 36

• Number of Participants Experiencing Injection-site Reactions (ISRs)

  Injection site reaction 1 = Redness, Injection site reaction 2 = Swelling, Injection site reaction 3 = Pain

  Up to Day 36

• Number of Participants Experiencing Serious Adverse Events (SAEs)

  Up to 38 weeks

• Pharmacodynamic Profile - Expression of IFN-responsive Genes (GBP-1, ISG-54, MCP-1, and MxB)

  Fold change of IFN-responsive gene expression relative to Day 8

  Change from Day 8 to Day 9

Secondary Outcomes (2)

• Number of Participants With Preliminary Response - Local (Injected Lesions)

  Up to 38 weeks

• Number of Participants With Preliminary Response - Systemic (Non-injected Lesions)

  Up to 38 weeks

Study Arms (1)

SD-101 in combination with low-dose radiation

EXPERIMENTAL

PART 1 * Radiation: 2 fractions of 2 Gy over 2 days at Days -1 and 1 * COHORT 1: 1 mg/mL at Days 1, 8, 15, 22, and 29 * COHORT 2: 2 mg/mL at Days 1, 8, 15, 22, and 29 * COHORT 3: 4 mg/mL at Days 1, 8, 15, 22, and 29 * COHORT 4: 8 mg/mL at Days 1, 8, 15, 22, and 29 PART 2 Cycle 1: Required * Radiation: 2 fractions of 2 Gy over 2 days at Days -1 and 1 * COHORT 1: 1 mg/mL at Days 1, 8, 15, 22, and 29 * COHORT 2: 8 mg/mL at Days 1, 8, 15, 22, and 29 Cycle 2: Optional * Radiation: 2 fractions of 2 Gy over 2 days at Days 180 and 181 * COHORT 1: 1 mg/mL at Days 181, 188, 195, 202, and 209 * COHORT 2: 8 mg/mL at Days 181, 188, 195, 202, and 209

Drug: SD-101; Radiation: Radiation therapy

Interventions

SD-101 DRUG

SD-101 in combination with low-dose radiation

Radiation therapy RADIATION

SD-101 in combination with low-dose radiation

Eligibility Criteria

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

You may qualify if:

• Biopsy confirmed, untreated, low-grade B-cell lymphoma, including follicular (Grade 1, 2, or 3A) \[Harris, Swerdlow et al. 2008\] or marginal, or CLL/SLL with lymph node involvement.
• At least 2 sites of measurable disease per Cheson criteria (must measure at least 1.5 cm in any diameter or 1.0 cm in the shortest diameter if one of the diameters is not ≥ 1.5 cm), one of which must be palpable and easily accessible in a low-risk site (eg, inguinal, axillary, cervical, subcutaneous) for intratumoral injection (denoted as "Lesion A" in Treatment Cycle 1) and at least one additional untreated lesion that is located outside the radiation field of the treated lesion (Lesion A) and is accessible for an FNA aspirate.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1
• Aged 18 years and older
• Absolute neutrophil count (ANC) ≥ 1500/mm3
• Platelet count \> 100,000/µL
• Serum creatinine (Cr) ≤ 1.5 x upper limit of normal (ULN).
• Serum total bilirubin ≤ 1.5 x the ULN.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
• International normalized ratio or prothrombin time (PT) ≤ 1.5 x ULN unless subject is receiving anticoagulant therapy and the PT or partial thromboplastin time (PTT) must be within the therapeutic range of the intended use of anticoagulants.
• Activated PTT (aPTT) ≤ 1.5 x ULN unless subject is receiving anticoagulant therapy, and the PT or PTT is within therapeutic range of intended use of anticoagulants.
• Female subjects must have a negative urine or serum pregnancy test within 72 hours prior to taking study medication if of childbearing potential as defined in this protocol. Women of childbearing potential (WOCBP) must be willing to use 2 medically acceptable method of contraceptive from Day 1 through 120 days after the last dose of trial treatment. The 2 medically acceptable birth control methods can be either 2 barrier methods or a barrier method plus a hormonal method to prevent pregnancy. The following are considered adequate barrier methods of contraception: diaphragm, condom (by the partner), cooper intrauterine device, sponge, or spermicide as per local regulations or guidelines. Appropriate hormonal contraceptives will include any registered and marketed contraceptive agent that contains an estrogen and/or a progestational agent (including oral, subcutaneous, intrauterine, or intramuscular agents).
• Ability to understand and sign informed consent form (ICF) and comply with treatment protocol

You may not qualify if:

• Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy (including immune modulators or systemic corticosteroids) within 7 days prior to study enrollment.
• Positive for hepatitis B (HBsAg reactive), HCV ribonucleic acid (RNA) qualitative, or human immunodeficiency virus (HIV)( HIV 1/2 antibodies)
• Diagnosis of mantle or diffuse large-cell lymphoma, Grade 3B follicular lymphoma \[Harris, Swerdlow et al. 2008\] or gastric mucosa-associated lymphoid tissue (MALT) lymphoma
• Clinically significant pleural effusion
• Active infection including cytomegalovirus
• Pregnant or breast feeding within the projected duration of trial participation through 4 months after the last dose of study treatment.
• Autoimmune disease including systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjӧgren's syndrome, autoimmune thrombocytopenia, history of uveitis, or other if clinically significant
• Lymphoma involvement of the central nervous system
• Received any prior therapy for lymphoma
• Use of any investigational agent within the last 28 days
• Serious, non-healing wound, ulcer, or bone fracture.
• If a subject received major surgery, must have recovered adequately from the toxicity and/or complications from the intervention prior to enrollment.
• Clinically significant cardiovascular disease (eg, uncontrolled hypertension, myocardial infarction, unstable angina), New York Heart Association (NYHA) Grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication within 1 year prior to Day -1 (Visit 1); Grade II or greater peripheral vascular disease at study entry
• Any other significant medical or psychiatric condition, laboratory abnormality, or difficulty complying with protocol requirements that may increase the risk associated with study participation or study drug administration that may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for this study
• History of sensitivity to any component of SD-101

Sponsors & Collaborators

• Dynavax Technologies Corporation: lead

Study Sites (5)

Stanford University School of Medicine

Stanford, California, 94305-5151, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Related Publications (1)

• Mooney KL, Czerwinski DK, Shree T, Frank MJ, Haebe S, Martin BA, Testa S, Levy R, Long SR. Serial FNA allows direct sampling of malignant and infiltrating immune cells in patients with B-cell lymphoma receiving immunotherapy. Cancer Cytopathol. 2022 Mar;130(3):231-237. doi: 10.1002/cncy.22531. Epub 2021 Nov 15.

  PMID: 34780125 DERIVED

MeSH Terms

Conditions

Lymphoma, B-Cell

Interventions

Radiotherapy

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

Intervention Hierarchy (Ancestors)

Therapeutics

Limitations and Caveats

The sponsor terminated the trial early because there was sufficient data to make a decision about SD-101 in the lymphoma development program.

Results Point of Contact

• Title: Robert Janssen MD \ VP & Chief Medical Officer
• Organization: Dynavax Technologies, Inc.

rjanssen@dynavax.com

510-665-0414

Study Officials

• Abraham Leung, MD

  Dynavax Technologies Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2014
• First Posted: October 16, 2014
• Study Start: October 1, 2014
• Primary Completion: April 1, 2017
• Study Completion: April 1, 2017
• Last Updated: September 4, 2020
• Results First Posted: September 4, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)