- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04316442
Study of the Safety and Efficacy of STI-6129 in Patients With Relapsed or Refractory Systemic AL Amyloidosis
A Phase 1b/2a, Open-Label, Dose-Escalation Study of the Safety and Efficacy of an Anti-CD38 Antibody Drug Conjugate (STI-6129) in Patients With Relapsed or Refractory Systemic AL Amyloidosis
The STI-6129-001 study is a three-stage, multicenter, open-label, dose-finding, phase 1b/2a trial. It is designed primarily to identify the recommended phase 2 dose (RP2D) of STI-6129 by assessing the safety, preliminary efficacy and pharmacokinetics of this anti-CD38-Duostatin 5.2 antibody-drug conjugate (ADC) for the treatment of relapsed or refractory systemic AL amyloidosis.
The patients that will be treated with STI-6129 in this trial are relapsed or refractory systemic AL amyloidosis patients who have received prior lines of treatment.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This study is composed of three dosing plan stages. The initial stage of this trial is the dose-escalation stage. A modified dose-escalation 3+3 design will be utilized to identify a safe maximum tolerated dose (MTD) of STI-6129 in patients with relapsed or refractory systemic AL amyloidosis. After identification of the MTD, or the finding that the last dosing cohort is tolerated well (i.e., the maximum practical dose [MPD]), 12 patients will be enrolled to receive STI-6129 treatment at the MTD/MPD level to collect pharmacokinetic data ( the pharmacokinetic (PK) stage) to model a treatment schedule that achieves a stable effective serum concentration. Results from the dose-escalation stage and the pharmacokinetic stage will be analyzed to develop a treatment dose/schedule for treating 30 additional patients enrolled in the expansion stage.
Each patient enrolled will receive up to three 4-week cycles of STI-6129, unless a longer intermission is required. After the treatment period, patients will be monitored for up to a year.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Ying Yan, MD MS
- Phone Number: 4183 858-203-4100
- Email: yyan@sorrentotherapeutics.com
Study Contact Backup
- Name: Mike Royal, MD JD MBA
- Phone Number: 4146 858-203-4100
- Email: mroyal@sorrentotherapeutics.com
Study Locations
-
-
California
-
Duarte, California, United States, 91010
- Recruiting
- City of Hope National Medical Center
-
Contact:
- Anju Nair
- Phone Number: 972-997-8000
- Email: annair@coh.org
-
Principal Investigator:
- Michael Rosenzweig, MD
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02118
- Recruiting
- Boston Medical Center
-
Contact:
- Melissa Difuntorum
- Phone Number: 617-638-8434
- Email: melissa.difuntorum@bmc.org
-
Principal Investigator:
- Vaishali Sanchorawala, MD
-
-
Michigan
-
Detroit, Michigan, United States, 48201
- Recruiting
- Barbara Ann Karmanos Cancer Institute Wertz Clinic
-
Contact:
- Silva Pregja
- Phone Number: 313-576-8766
- Email: pregjas@karmanos.org
-
Principal Investigator:
- Jeffrey Zonder, MD
-
-
Wisconsin
-
Milwaukee, Wisconsin, United States, 53226
- Recruiting
- Froedtert Hospital & the Medical College of Wisconsin
-
Contact:
- Althea Thomas
- Phone Number: 414-805-2588
- Email: athomas@mcw.edu
-
Contact:
- Nicholas Mohrdieck
- Phone Number: 414-805-6402
- Email: nmohrdieck@mcw.edu
-
Principal Investigator:
- Anita D'Souza, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Confirmed diagnosis of AL amyloidosis by tissue biopsy of an involved organ, or a surrogate site such as abdominal fat demonstrating amyloid deposition by mass spectrometry
- The presence of a monoclonal light chain protein in serum
- Relapsed or refractory AL amyloidosis is defined as patients who have received ≥ 2 lines of treatment. Patients must have received at least one proteasome inhibitor during their prior therapy. Patients who have received prior daratumumab treatment or prior stem cell transplantation remain eligible. Patients may have relapsed with disease progression or have been refractory to their last prior line of treatment. Progression of disease that develops > 60 days after the last dose of a treatment regimen in a patient who achieved at least a partial response (PR) defines a relapse. Refractory systemic AL amyloidosis is defined as the development of disease progression during therapy with an anti-AL amyloidosis treatment regimen or within 60 days of the last dose of an anti-AL amyloidosis treatment regimen or the achievement of less than a PR after ≥ 2 cycles
- Measurable disease defined as the finding by serum-free light chain (FLC) assay that the difference between the involved and uninvolved FLC (dFLC) is ≥ 50 mg/L
- Pulse oximetry ≥ 92% on room air
- ECOG performance status of 0, 1, or 2
- Willing to comply with the study schedule and all other protocol requirements
- Females of childbearing potential (FCBP) must have 2 negative pregnancy tests prior to treatment. All heterosexually active FCBP and all heterosexually active male patients must agree to use effective methods of birth control throughout the study
Exclusion Criteria:
- Isolated vascular amyloid in a bone marrow biopsy or a plasmacytoma specimen or isolated soft tissue involvement (localized AL amyloidosis)
- Presence of non-AL amyloidosis
- A diagnosis of multiple myeloma
- A diagnosis of other malignancies if the malignancy has required therapy within the last 3 years or is not in complete remission. Exceptions are non-metastatic basal cell or squamous cell carcinomas of the skin or prostate cancer that does not require treatment
- Treatment with an allogeneic hematopoietic stem cell transplantation (HSCT) within 6 months prior to the planned infusion of STI-6129, or active graft-versus-host disease (GVHD) following the allogeneic transplant, or a requirement for currently receiving immunosuppressive therapy following the allogeneic transplant
- Revised Mayo Clinic AL amyloidosis stage > 3
- New York Heart Association (NYHA) class > 2
- Left ventricular ejection fraction (LVEF) < 40%
- Patients with mean left ventricular wall thickness ≥ 12 mm and/or intraventricular septal thickness > 25 mm by echocardiogram in the absence of hypertension or valvular heart disease
- Patients with NT-proBNP ≥ 1800 ng/L or BNP ≥ 400 ng/L, or cTNT ≥ 0.025 μg/L will be excluded in the dose-escalation stage of the study and can only be included in the PK and expansion stages after evaluation by cardiology and discussion with the principle investigator regarding the risk associated with the treatment
Abnormal baseline hematological laboratory results at Screening:
- Hemoglobin < 8.0 g/dL
- Platelet count < 50,000/μL
- Absolute neutrophil count (ANC) < 1000/μL
Abnormal baseline chemistry laboratory results at Screening:
- Serum creatinine ≥ 2.0 mg/dL or estimated creatinine clearance < 60 mL/min (using the Cockcroft-Gault equation)
- Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3x the upper limit of normal (ULN) or serum total bilirubin > 1.5x ULN (except for patients in whom hyperbilirubinemia is attributed to Gilbert's Syndrome)
- INR or aPTT > 1.5x ULN within 1 week prior to the infusion of STI-6129, unless on a stable dose of an anticoagulant
- Pregnant or breastfeeding
- Active bacterial, viral, or fungal infection within 72 hours of the infusion of STI-6129; patients with ongoing use of prophylactic antibiotics, antifungal agents, or antiviral agents remain eligible as long as there is no evidence of active infection
- Have human immunodeficiency virus (HIV) infection, human T-cell leukemia virus type 1 (HTLV1) infection, or hepatitis B virus (HBV) or hepatitis C virus (HCV) viremia or are at risk for HBV reactivation (at risk for HBV reactivation is defined as being HBs antigen positive, or anti-HBc-antibody positive), or are positive for HBV deoxyribonucleic acid (DNA). HCV ribonucleic acid (RNA) must be undetectable by laboratory test
- QTcF > 470 msec on a baseline ECG
- Any condition including the presence of laboratory abnormalities that places the patient at unacceptable risk if the patient was to participate in the study
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: STI-6129 infusion
Intravenous infusion to be given with prophylaxis for infusion reactions if necessary.
|
Four cycles of intravenous infusion of STI-6129 will be given (one infusion every four weeks).
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety and tolerability of STI-6129 in AL amyloidosis patients
Time Frame: Baseline through study completion at up to 14 months
|
Types, frequencies, and severities of adverse events (AEs) and the relationships of AEs to study drug; includes serious adverse events (SAEs), neurotoxicity, dose-limiting toxicities (DLTs), and laboratory abnormalities
|
Baseline through study completion at up to 14 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall hematological response rate according to the 2012 Consensus Round Table response criteria
Time Frame: Baseline through study completion at up to 14 months
|
Proportion of subjects with Complete Response (CR), Very Good Partial Response (VGPR), Partial Response (PR), No Response (NR) and Progressive Disease (PD)
|
Baseline through study completion at up to 14 months
|
Organ response rates (cardiac, renal, hepatic, peripheral nervous system) according to the 2012 Consensus Round Table response criteria
Time Frame: Baseline through study completion at up to 14 months
|
Organ response rates (cardiac, renal, hepatic, peripheral nervous system) according to the 2012 Consensus Round Table response criteria
|
Baseline through study completion at up to 14 months
|
Correlation of treatment response (organ responses and hematological response) with disease severity based on the 2012 revised Mayo Clinic staging system for AL amyloidosis
Time Frame: Baseline through study completion at up to 14 months
|
Correlation of treatment response (organ responses and hematological response) with disease severity based on the 2012 revised Mayo Clinic staging system for AL amyloidosis
|
Baseline through study completion at up to 14 months
|
Plasma levels of the total antibody plus conjugated toxin (STI-6129) and the free toxin (Duostatin 5.2)
Time Frame: Day 1 to day 63
|
Plasma levels of the total antibody plus conjugated toxin (STI-6129) and the free toxin (Duostatin 5.2) by ELISA and mass spectrophotometry assays, respectively, at pre-dose and various time points post-dose
|
Day 1 to day 63
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Michael Rosenzweig, MD, City of Hope National Medical Center
- Principal Investigator: Jeffrey Zonder, MD, Barbara Ann Karmanos Cancer Institute Wertz Clinic
- Principal Investigator: Anita D'Souza, MD, Froedtert Hospital & the Medical College of Wisconsin
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Metabolic Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Paraproteinemias
- Proteostasis Deficiencies
- Neoplasms, Plasma Cell
- Immunoglobulin Light-chain Amyloidosis
- Amyloidosis
- Physiological Effects of Drugs
- Immunologic Factors
- Immunoconjugates
Other Study ID Numbers
- STI-6129-001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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.
Clinical Trials on Light Chain (AL) Amyloidosis
-
Peking Union Medical College HospitalRecruitingLight Chain (AL) Amyloidosis | Venetoclax | CCND1 TranslocationChina
-
Tufts Medical CenterSanofiWithdrawnAmyloidosis | Light Chain (AL) Amyloidosis
-
Alfred Chung, MDAbbVie; Janssen PharmaceuticalsRecruitingAL Amyloidosis | Light Chain (AL) Amyloidosis | Systemic Light Chain DiseaseUnited States
-
Sorrento Therapeutics, Inc.WithdrawnLight Chain (AL) Amyloidosis
-
European Myeloma NetworkJanssen PharmaceuticaActive, not recruitingLight Chain (AL) Amyloidosis, Stage 3BNetherlands, Greece, France, Italy
-
Nexcella Inc.Not yet recruitingLight Chain (AL) AmyloidosisUnited States
-
Prothena Biosciences Ltd.RecruitingLight Chain (AL) AmyloidosisUnited States, Korea, Republic of, Australia, Denmark, France, Italy, Spain, Israel, Taiwan, Austria, Canada, Czechia, Germany, Greece, Hungary, Ireland, Japan, Netherlands, Poland, Portugal, Turkey, United Kingdom, Belgium
-
Air Force Military Medical University, ChinaNot yet recruitingImmunoglobulin Light-chain Amyloidosis
-
AbbVieNot yet recruiting
-
Florian MichelGerman Federal Ministry of Education and ResearchCompletedLight Chain (AL) Amyloidosis | Cardiac InvolvementGermany
Clinical Trials on STI-6129
-
M.D. Anderson Cancer CenterWithdrawnSTI-6129 CD38 ADC for the Treatment of Patients With Relapsed or Refractory Systemic ALL AmyloidosisAcute Myeloid Leukemia (AML) | Refractory T Acute Lymphoblastic LeukemiaUnited States
-
Zhejiang ACEA Pharmaceutical Co. Ltd.RecruitingRelapsed or Refractory Multiple MyelomaChina
-
Sorrento Therapeutics, Inc.Active, not recruitingMultiple MyelomaUnited States
-
Sorrento Therapeutics, Inc.Not yet recruitingAdvanced Solid TumorUnited States
-
Sorrento Therapeutics, Inc.WithdrawnLight Chain (AL) Amyloidosis
-
Zhejiang ACEA Pharmaceutical Co. Ltd.Completed
-
Zhejiang ACEA Pharmaceutical Co. Ltd.Recruiting
-
Children's Hospital Medical Center, CincinnatiEunice Kennedy Shriver National Institute of Child Health and Human Development... and other collaboratorsActive, not recruitingChlamydia | GonorrheaUnited States
-
Columbia UniversityCompletedSexually Transmitted InfectionsUnited States
-
Sorrento Therapeutics, Inc.RecruitingMultiple MyelomaUnited States