| Eligibility |
Inclusion Criteria:
- 1. Age = 18 years.
- 2. 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
- 3. The presence of a monoclonal light chain protein in serum and/or urine
- 4. Relapsed or refractory (R/R) AL amyloidosis is patients who have exhausted standard
of care treatment. Patients who have received prior CD38-directed monoclonal antibody
(e.g. daratumumab, isatuximab) 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. 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
- 5. Measurable disease defined by the following: the finding by serum FLC assay that
the difference between the involved and uninvolved FLC (dFLC) is = 40 mg/L
- 6. Pulse oximetry = 92% on room air
- 7. ECOG performance status of 0, 1, or 2
- 8. Be willing and able to comply with the study schedule and all other protocol
requirements
- 9. Willing to follow contraception guidelines: c. If a female, be sterile (surgically
or biologically)* or at least one year post-menopausal, or have a monogamous partner
who is surgically sterile, or have a same sex partner, or if in a heterosexual
relationship, must agree to do the following during the study after completing IP
dosing:
- Practice abstinence (only considered an acceptable method of contraception when
it is in line with the participants' usual and preferred lifestyle)
- Use at least one of the following medically acceptable methods of birth control:
- Hormonal methods as follows:
- Combined estrogen and progestogen containing hormonal contraception associated
with inhibition of ovulation (oral, intravaginal, transdermal)
- Progestogen only hormonal contraception associated with inhibition of ovulation
(oral, injectable, implantable)
- Intrauterine devices
- Intrauterine hormone-releasing systems
- Vasectomized partner
- Barrier contraception
- Defined as having had a hysterectomy and/or bilateral oophorectomy, bilateral
salpingectomy or bilateral tubal ligation/occlusion at least 6 weeks prior to
screening; or having a congenital or acquired condition that prevents
childbearing.
d. If a male of reproductive potential, unless he has a same sex partner, must
agree to do the following during the study after completing IP dosing:
- Refrain from donating sperm
- Practice abstinence from heterosexual activity (only considered an
acceptable method of contraception when it is in line with the participants'
usual and preferred lifestyle), OR
- Use (or have their partner use) acceptable contraception (see criterion
above) during heterosexual activity, such as barrier contraception
Exclusion Criteria:
- 1. Isolated vascular amyloid in a bone marrow biopsy or a plasmacytoma specimen or
isolated soft tissue involvement (localized AL amyloidosis)
- 2. Presence of non-AL amyloidosis
- 3. A diagnosis of multiple myeloma
- 4. 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 or in situ cancer that does
not require treatment or is well under control
- 5. 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
- 6. Revised Mayo Clinic AL amyloidosis stage > 3
- 7. New York Heart Association (NYHA) class > 3
- 8. Left ventricular ejection fraction (LVEF) < 40%.
- 9. Patients with mean left ventricular wall thickness = 15 mm and/or intraventricular
septal thickness > 25 mm by echocardiogram in the absence of hypertension or valvular
heart disease
- 10. Patients with NT-proBNP = 1800 ng/L or BNP = 400 ng/L, cTnT = 0.025 mcg/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
- 11. The following baseline hematological laboratory results at Screening (these
results must be independent of blood product or hematopoietic growth factor support):
1. Hemoglobin < 8.0 g/dL
2. Platelet count < 50,000/µL
3. Absolute neutrophil count (ANC) < 1000/ µL
- 12. The following baseline chemistry laboratory results at Screening:
1. Serum creatinine > 2.0 x the upper limit of normal (ULN), or estimated creatinine
clearance < 45 mL/min (using the Cockcroft-Gault equation).
2. Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3x ULN
or serum total bilirubin > 1.5x ULN (except for patients in whom
hyperbilirubinemia is attributed to Gilbert's Syndrome)
- 13. INR or aPTT > 1.5x ULN within 1 week prior to the infusion of STI-6129, unless on
a stable dose of an anticoagulant
- 14. Are pregnant or breastfeeding
- 15. Patients with = Grade 3 neuropathy or Grade 2 neuropathy with associated pain
- 16. 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,
or the STI-6129 treatment would put the patient at risk for a meaningful safety event.
- 17. Have a prolongation in QTcF (Fridericia correction formula) > 480 msec on a
baseline ECG
- 18. Any condition including the presence of laboratory abnormalities that places the
patient at an unacceptable risk if the patient was to participate in the study
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