Study of the Safety and Efficacy of STI-6129 in Patients With Relapsed or Refractory Systemic AL Amyloidosis

NCT ID: NCT04316442

Last Updated: 2023-01-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1/PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-04-01

Study Completion Date

2024-12-31

Brief Summary

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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

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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

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Light Chain (AL) Amyloidosis

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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STI-6129 infusion

Intravenous infusion to be given with prophylaxis for infusion reactions if necessary.

Group Type EXPERIMENTAL

STI-6129

Intervention Type BIOLOGICAL

Four cycles of intravenous infusion of STI-6129 will be given (one infusion every four weeks).

Interventions

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STI-6129

Four cycles of intravenous infusion of STI-6129 will be given (one infusion every four weeks).

Intervention Type BIOLOGICAL

Other Intervention Names

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anti-CD38-Duostatin 5.2 antibody-drug conjugate (ADC)

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sorrento Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Vaishali Sanchorawala, MD

Role: PRINCIPAL_INVESTIGATOR

Boston Medical Center

Michael Rosenzweig, MD

Role: PRINCIPAL_INVESTIGATOR

City of Hope National Medical Center

Jeffrey Zonder, MD

Role: PRINCIPAL_INVESTIGATOR

Barbara Ann Karmanos Cancer Institute Wertz Clinic

Anita D'Souza, MD

Role: PRINCIPAL_INVESTIGATOR

Froedtert Hospital & the Medical College of Wisconsin

Locations

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City of Hope National Medical Center

Duarte, California, United States

Site Status RECRUITING

Boston Medical Center

Boston, Massachusetts, United States

Site Status RECRUITING

Barbara Ann Karmanos Cancer Institute Wertz Clinic

Detroit, Michigan, United States

Site Status RECRUITING

Froedtert Hospital & the Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Ying Yan, MD MS

Role: CONTACT

858-203-4100 ext. 4183

Mike Royal, MD JD MBA

Role: CONTACT

858-203-4100 ext. 4146

Facility Contacts

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Anju Nair

Role: primary

972-997-8000

Melissa Difuntorum

Role: primary

617-638-8434

Silva Pregja

Role: primary

313-576-8766

Althea Thomas

Role: primary

414-805-2588

Nicholas Mohrdieck

Role: backup

414-805-6402

Other Identifiers

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STI-6129-001

Identifier Type: -

Identifier Source: org_study_id

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