Study of GC012F, CAR-T Therapy Targeting CD19 and BCMA in Chinese Participants With Relapsed or Refractory AL Amyloidosis

Inclusion Criteria

• Inclusion Criteria:
• 1. Confirmed histopathological diagnosis of AL amyloidosis
• 2. One or more organs currently or historically impacted by AL amyloidosis according to consensus guidelines
• 3. Measurable hematologic disease: dFLC > 20 mg/L or serum M-protein > 5g/L
• 4. Relapsed disease or refractory disease defined as a need for additional therapy after at least 1 line of anti-plasma cell-directed therapy.
• 5. ECOG performance status of 0 to 1
• 6. Must be able and willing to adhere to the study visit schedule and other protocol requirements
• 7. Women 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.
• Exclusion Criteria:
• 1. Have any other form of amyloidosis other than AL amyloidosis
• 2. Mayo Stage IIIb AL amyloidosis
• 3. Oxygen saturation < 95% on room air
• 4. Systolic blood pressure <100mmHg
• 5. Cardiac exclusion criteria:
• a. Mayo Stage IIIb AL amyloidosis (Wechalekar, 2013)
• b. NT-proBNP levels as follows:
• NT-proBNP ≥ 2000 ng/L (for dose escalation portion)
• NT-proBNP < 2000 and > 5000 ng/L (for dose extension portion)
• c. High-sensitivity cardiac troponin T > 75 ng/L
• d. NYHA class III or IV
• 5. Extensive GI involvement with evidence of active GI bleeding/risk of bleeding as determined by Investigator
• 6. Prior therapies:
• 1) CAR T cell therapy directed at any target
• 2) Prior BCMA-targeting therapy
• 3) Prior treatment with any approved or investigational T cell engaging therapies (including T cell-directed bispecific or trispecific therapies) at any target within the last 6 months.
• 7. Toxicity from previous anti-cancer or anti-PC-directed therapy did not resolve to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy.
• 8. Active plasma cell leukemia at the time of screening
• 9. Multiple myeloma defined as clonal bone marrow PCs ≥10% and any one or more of the following myeloma defining events (deemed as attributable to multiple myeloma by Investigator) (Rajkumar, 2014)
• 10. Seropositive for HIV
• 11. Serologic status reflecting active hepatitis B or C:
• a. Positive HBsAg, or
• b. Patients with positive core antibody (anti-HBc) and HBV-DNA positive.
• c. Patients with positive hepatitis C antibody and HCV RNA positive.