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

August 20, 2020 updated by: Dynavax Technologies Corporation

A Phase 1/2, Non-randomized, Open-label, Multicenter, Dose Escalation and Expansion Study of Intratumoral Injections of SD-101 in Combination With Localized Low-dose Radiation in Patients With Untreated Low-grade B-cell Lymphoma

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

29

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Stanford, California, United States, 94305-5151
        • Stanford University School of Medicine
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Hospitals and Clinics
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • New York
      • Rochester, New York, United States, 14642
        • University of Rochester Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • A diagnosis of cancer within the last 3 years prior to enrollment or any known additional malignancy that is progressing or requires active treatment. Exceptions are B-cell lymphoma, basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, and in situ cervical cancer.
  • Is taking systemic corticosteroids (more than 3 consecutive days) or other immunomodulators or immune suppressive medication

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: SD-101 in combination with low-dose radiation

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
Radiation: Radiation therapy
Drug: SD-101

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Experiencing Dose-limiting Toxicities (DLTs) and Maximum Tolerated Dose (MTD).
Time Frame: Up to Day 36
Up to Day 36
Number of Participants Experiencing Injection-site Reactions (ISRs)
Time Frame: Up to Day 36
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)
Time Frame: Up to 38 weeks
Up to 38 weeks
Pharmacodynamic Profile - Expression of IFN-responsive Genes (GBP-1, ISG-54, MCP-1, and MxB)
Time Frame: Change from Day 8 to Day 9
Fold change of IFN-responsive gene expression relative to Day 8
Change from Day 8 to Day 9

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Preliminary Response - Local (Injected Lesions)
Time Frame: Up to 38 weeks
Subjects with maximum decrease of 50% or greater in sum of products of diameters of lesions.
Up to 38 weeks
Number of Participants With Preliminary Response - Systemic (Non-injected Lesions)
Time Frame: Up to 38 weeks
Subjects with maximum decrease of 50% or greater in sum of products of diameters of lesions.
Up to 38 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Dynavax Technologies Corporation

Investigators

  • Study Director: Abraham Leung, MD, Dynavax Technologies Corporation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2014

Primary Completion (Actual)

April 1, 2017

Study Completion (Actual)

April 1, 2017

Study Registration Dates

First Submitted

October 13, 2014

First Submitted That Met QC Criteria

October 13, 2014

First Posted (Estimate)

October 16, 2014

Study Record Updates

Last Update Posted (Actual)

September 4, 2020

Last Update Submitted That Met QC Criteria

August 20, 2020

Last Verified

August 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DV3-LYM-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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