Light Chain (AL) AmyloidosisPhase 1/2NCT04316442
Study of the Safety and Efficacy of STI-6129 in Patients With Relapsed or Refractory Systemic AL Amyloidosis
A Phase 1/2 study testing STI-6129 in people with Light Chain (AL) Amyloidosis, run by Sorrento Therapeutics, Inc. at 4 sites in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Light Chain (AL) Amyloidosis
- What is being tested?
- STI-6129
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 4 sitesUnited States
- Study dates
- 1 Apr 2021to Dec 2024
- Phase
- Phase 1/2
- 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
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
4 sites in 1 country.
United States4 sites, 4 recruiting
- Recruiting
Boston Medical Center
Boston, Massachusetts, 02118
Melissa Difuntorum, 617-638-8434, melissa.difuntorum@bmc.org
Vaishali Sanchorawala, MD
- Recruiting
Barbara Ann Karmanos Cancer Institute Wertz Clinic
Detroit, Michigan, 48201
Silva Pregja, 313-576-8766, pregjas@karmanos.org
Jeffrey Zonder, MD
- Recruiting
City of Hope National Medical Center
Duarte, California, 91010
Anju Nair, 972-997-8000, annair@coh.org
Michael Rosenzweig, MD
- Recruiting
Froedtert Hospital & the Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Althea Thomas, 414-805-2588, athomas@mcw.edu
Nicholas Mohrdieck, 414-805-6402, nmohrdieck@mcw.edu
About this study
Official title: 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.
Read the 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.
- Conditions
- Light Chain (AL) Amyloidosis
- Being tested
- STI-6129
- Medical subject headings
- Amyloidosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
STI-6129Biological
Also called anti-CD38-Duostatin 5.2 antibody-drug conjugate (ADC)
Four cycles of intravenous infusion of STI-6129 will be given (one infusion every four weeks).
| Study group | Role | What they receive |
|---|---|---|
| STI-6129 infusion | Experimental | Intravenous infusion to be given with prophylaxis for infusion reactions if necessary. Receives: Biological: STI-6129 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of STI-6129 in AL amyloidosis patients
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
Measured: Baseline through study completion at up to 14 months
Secondary outcomes (4)
Overall hematological response rate according to the 2012 Consensus Round Table response criteria
Proportion of subjects with Complete Response (CR), Very Good Partial Response (VGPR), Partial Response (PR), No Response (NR) and Progressive Disease (PD)
Measured: 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
Organ response rates (cardiac, renal, hepatic, peripheral nervous system) according to the 2012 Consensus Round Table response criteria
Measured: 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
Correlation of treatment response (organ responses and hematological response) with disease severity based on the 2012 revised Mayo Clinic staging system for AL amyloidosis
Measured: 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)
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
Measured: Day 1 to day 63
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2020
- Study start1 Apr 2021
- Primary completionSep 2024 (estimated)
- Study completionDec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Light Chain (AL) AmyloidosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sorrento Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Vaishali Sanchorawala, MD, Principal investigator, Boston Medical CenterMichael Rosenzweig, MD, Principal investigator, City of Hope National Medical CenterJeffrey Zonder, MD, Principal investigator, Barbara Ann Karmanos Cancer Institute Wertz ClinicAnita D'Souza, MD, Principal investigator, Froedtert Hospital & the Medical College of Wisconsin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04316442
- Sponsor's protocol ID
- STI-6129-001
- Status last verified
- Jan 2023
- First submitted
- 16 Mar 2020
- Last updated
- 17 Jan 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04316442
- Acronym / sponsor ID
- STI-6129-001
- Conditions
- Light Chain (AL) Amyloidosis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Sorrento Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 1 Apr 2021 (actual)
- Primary completion
- Sep 2024 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 20 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| STI-6129 infusion | Experimental | Biological: STI-6129Intravenous infusion to be given with prophylaxis for infusion reactions if necessary. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (23 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| STI-6129Also: anti-CD38-Duostatin 5.2 antibody-drug conjugate (ADC)Four cycles of intravenous infusion of STI-6129 will be given (one infusion every four weeks). | Biological | STI-6129 infusion |
Primary outcome
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
4 secondary outcomes
Overall hematological response rate 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
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
Time frame: 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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jan 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vaishali Sanchorawala, MD principal investigator
Boston Medical Center
Michael Rosenzweig, MD principal investigator
City of Hope National Medical Center
Jeffrey Zonder, MD principal investigator
Barbara Ann Karmanos Cancer Institute Wertz Clinic
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing STI-6129 in people with Light Chain (AL) Amyloidosis, run by Sorrento Therapeutics, Inc. at 4 sites in United States.
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 8 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: status not confirmed, as of the sponsor's last update on 17 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ying Yan, MD MS (858-203-4100 ext. 4183, yyan@sorrentotherapeutics.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability of STI-6129 in AL amyloidosis patients (time frame: Baseline through study completion at up to 14 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 17 Jan 2023.