Renal AL Amyloid Involvement and NEOD001

• Status: Terminated
• Trial end date: 2019-02-06
• Target enrollment: 0
• Participant gender: All

Summary

This is a multicenter, Phase 2b, randomized, double-blind, placebo-controlled, two-arm, parallel-group efficacy and safety study of NEOD001 as a single agent administered intravenously in adults with AL amyloidosis who have a maintained hematologic response to their most recent treatment for AL amyloidosis (e.g., chemotherapy, autologous stem cell transplant [ASCT]) and have persistent renal dysfunction.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Tufts Medical Center

Criteria

Inclusion Criteria:

1. 18 years of age or older

2. Biopsy-proven diagnosis of AL amyloidosis by immunohistochemistry or mass spectroscopy of a tissue biopsy excluding bone marrow

3. Screening renal biopsy for RAIN confirming AL amyloidosis as exclusive or dominant cause of renal damage

4. Persistent renal involvement from diagnosis with proteinuria (predominantly albumin) > 500mg/day in a 24-hour urine collection

5. CKD 1 to 3 (eGFR > 30)

6. ≥1 prior systemic hematologic therapy for a free light chain (FLC) producing hematologic malignancy underlying the initial diagnosis of AL amyloidosis with at least a partial FLC response (PR, VGPR, CR) to treatment deemed stable and not requiring further treatment

7. ECOG Performance Status ≤ 2

8. Clinical laboratory values:

1. Absolute neutrophil count > 1000/μL

2. Platelet count > 75,000/μL

3. Total bilirubin ≤ 1.5X ULN

4. Alkaline phosphatase ≤ 5X ULN

5. NT-proBNP < 1800 pg/mL

9. Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care

Exclusion Criteria:

1. Amyloidosis due to mutations of the transthyretin gene or presence of other non-AL amyloidosis

2. Female patients who are lactating, breastfeeding, or pregnant

3. Patients who have not been treated or who have received chemotherapy within 6 months, or SCT within 12 months, for the light-chain producing hematologic disease causing AL amyloidosis, at the time of the first dose of NEOD001 (month 1 day 1)

4. Patients who at initial diagnosis or later met the International Myeloma Working Group (IMWG) definition of active multiple myeloma requiring therapy (Appendix 3)

5. Patients whose screening renal biopsies for RAIN show dominant causes of renal damage not related to AL amyloidosis

6. Medically documented cardiac syncope, uncompensated congestive heart failure, myocardial infarction within the previous 6 months, unstable angina pectoris, clinically significant repetitive atrial or ventricular arrhythmias despite antiarrhythmic treatment, or severe orthostatic hypotension or clinically significant uncompensated autonomic insufficiency

7. Comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens

8. Ongoing or active infection, known HIV positive, known to be hepatitis B surface antigen-positive or has known or suspected active hepatitis C infection.

9. Psychiatric illness/social situations that would limit compliance with study requirements