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Official Title

Phase 1b/2 Study of NXC-201 for the Treatment of Patients With Relapsed or Refractory AL Amyloidosis

Phase
Phase 1/Phase 2
Sponsor
Nexcella Inc.
Enrollment
40
Timeline
Jun 2024 → Jan 2039
About This Study

Open-label Phase 1b Dose Escalation/Dose Expansion study exploring the safety and efficacy of NXC-201 in patients with relapsed or refractory light chain amyloidosis (AL).

Eligibility Criteria

Inclusion Criteria

  • 1≥18 years of age.
  • 2Voluntarily signed informed consent form (ICF).
  • 3Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
  • 4Histologically proven systemic AL amyloidosis confirmed by positive Congo red staining with green birefringence on polarized light microscopy in an organ outside the bone marrow and evidence of a measurable clonal plasma cell disease that requires active treatment.
  • 5An underlying plasma cell disorder can be identified by one of the following: clonal plasma cells in the BM, monoclonal protein in the serum or urine, or abnormal free light chain ratio.
  • 6Because AL amyloidosis may present with low volumes of bone marrow plasma cells, prior biopsies demonstrating clonal plasma cell populations may be used to determine eligibility.
  • 7Measurable hematologic disease: difference between involved and uninvolved FLC \> 20 mg/L (or 2mg/dl) with an abnormal k/l ratio; or M-spike \> 0.5mg/dl.
  • 8Patients should have received at least one line of therapy with a CD38 monoclonal antibody and a proteosome inhibitor and not be in VGPR or CR at the time of inclusion. Patients who did not reach VGPR after two cycles of initial therapy or patients who did achieve VGPR or better but with a hematological relapse can be included.
  • 9Symptomatic organ involvement (heart, kidney, liver/GI tract, peripheral nervous system).
  • 10Women of child-bearing potential (WCBP) must have a negative serum pregnancy test prior to treatment. All sexually active WCBP and all sexually active male subjects must agree to use effective methods of birth control throughout the study.
  • 11Recovery to ≤Grade 2 or baseline of any non-hematologic toxicities due to prior treatments, excluding alopecia and Grade 3 neuropathy.
  • 12Absence of any psychological, familial, sociological, or geographical conditions potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before trial entry.
  • 13Able to swallow pills.

Exclusion Criteria

  • 1Prior treatment with CAR T therapy directed at any target.
  • 2Any therapy that is targeted to BCMA.
  • 3Stroke or seizure within 6 months of signing ICF.
  • 4Bone marrow plasma cells \>30% and clinically symptomatic multiple myeloma with end organ damage (i.e. lytic bone lesions).
  • 5New York Heart Association Heart Failure Class III or Class IV.
  • 6Any prior systemic therapy for AL amyloidosis within 14 days prior to leukapheresis.
  • 7Therapeutic doses of steroids within 2 weeks prior to leukapheresis (Physiological replacement doses of steroids are allowed up to 12 mg/m2/d hydrocortisone or equivalent).
  • 8Any prior systemic therapy for AL amyloidosis within 14 days of leukapheresis.
  • 9Wash-out period of at least 4 weeks from previous investigational treatment prior to leukapheresis.
  • 10Inadequate hepatic function:
  • 11Aspartate aminotransferase (AST \[SGOT\] or alanine aminotransferase (ALT \[SGPT\]) \>3 x upper limit of normal (ULN) value
  • 12Alkaline phosphatase \>2 times ULN
  • 13Serum direct bilirubin \>2 times ULN
  • 14Inadequate renal function: creatinine clearance (CRCL) \<20 mL/min.
  • 15Inadequate bone marrow function prior to leukapheresis or lymphodepletion, without transfusion or growth factor support within 5 days prior defined by absolute neutrophil count (ANC) \<1000 cells/mm3, platelet count \<50,000/mm3, or hemoglobin \<8 g/dL (blood transfusions are allowed), absolute lymphocyte count \< 300 cells/mm3.
  • 16Presence of active infection within 72 hours prior to lymphodepletion.
  • 17Significant co-morbid condition/s or disease/s which in the judgment of the Investigator would place the subject at undue risk or interfere with the study.
  • 18Known human immunodeficiency virus (HIV) positive status subjects who have not achieved undetectable viral load on highly active anti-retroviral therapy/combination anti-retroviral therapy (HAART/cART) within 6 months of lymphodepletion (previously treated HIV with undetectable viral load can be included)
  • 19Patients with active Hepatitis B or Hepatitis C with detectable viral load (previously treated Hepatitis B or Hepatitis C with undetectable viral load can be included)
  • 20Subjects with a history of stroke, unstable angina, or myocardial infarction requiring medication or mechanical control within 3 months.
  • 21Evidence of clinically significant ventricular arrhythmias on 7-day Zio® patch (or equivalent device) monitoring despite anti-arrhythmic treatment, except if a pacemaker or automated implantable cardioverter defibrillator (AICD) has been implanted.
  • 22Stage IIIb patients:
  • 23NT-proBNP \>8500 ng/L and
  • 24hs-troponin I ≥100 ng/L or troponin I ≥0.1 mcg/L or troponin T ≥ 0.035 mcg/L or hs-troponin T ≥50 ng/L
  • 25Left ventricular ejection fraction \<35%.
  • 26Heart failure which is, in the opinion of the Investigator, related to ischemic heart disease.
  • 27Presence of other active malignancy that requires treatment with the exception of non-melanoma skin cancer, cervical cancer, treated early-stage prostate cancer provided that prostate specific antigen is within normal limit, or any completely resected carcinoma in situ; other indolent/completely resected malignancies may be discussed with the Principal Investigator (PI) and/or Co-PI.
  • 28Subjects who have had a venous thromboembolic event requiring anticoagulation and who meet any of the following criteria:
  • 29Have been on a stable dose of anticoagulation for \< 1 month (except for acute line insertion induced thrombosis).
  • 30Have had a Grade 2, 3, or 4 hemorrhage in the last 30 days.
  • 31Are experiencing continued symptoms from their venous thromboembolic event (e.g., continued dyspnea or oxygen requirement).
  • 32Presence of non-AL amyloidosis.
  • 33AL amyloidosis with isolated soft tissue involvement.
  • 34Supine systolic blood pressure \<100 mmHg or postural symptoms despite medical therapy.
  • 35Subject is a woman who is pregnant, or breast-feeding, or planning to become pregnant.
  • 36Subjects with known/underlying medical conditions that, in the investigator's opinion would make the administration of the study drug hazardous (i.e., chronic obstructive pulmonary disease, persistent asthma, uncontrolled diabetes or uncontrolled coronary artery disease).
  • 37Chronic atrial fibrillation with uncontrolled heart rate.
  • 38Unwillingness to practice effective birth control.
  • 39Inability to comply with other requirements of the protocol.

Locations

18 sites participating in this study

Winship Cancer Institute, Emory University

Atlanta, Georgia 30322

Recruiting

Jonathan Kaufman, MD

Sutter Health Alta Bates

Berkeley, California 94704

Recruiting

Oleg Krijanovski, MD

City of Hope

Duarte, California 91010

Recruiting

Michael A Rosenzweig, MD

Data sourced from ClinicalTrials.govView on ClinicalTrials.gov →