Safety and Efficacy of AMG 420 in Subjects with With Relapsed and/or Refractory Multiple Myeloma

Phase 1

• Conditions: Relapsed or Refractory Multiple Myeloma; MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-002879-17-FR
• Lead Sponsor: Amgen Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-08-05
• Last Update Posted: 25 November 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 120

Inclusion Criteria

Subject has provided informed consent prior to initiation of any study specific activities/procedures.
Age ? 18 years at the time of the signing of informed consent.
Multiple myeloma meeting the following criteria:
•Pathologically-documented diagnosis of multiple myeloma that is relapsed or is refractory as defined by the following:
?Relapsed after ? 3 lines of prior therapy that must include a PI, an IMiD, and a CD38-directed monoclonal antibody in any order during the course of treatment OR refractory to PI, IMiD, and CD38-directed monoclonal antibody.
•Measurable disease, defined by 1 or more of the following at time of screening:
?serum M-protein > 0.5 g/dL measured by serum protein electrophoresis (SPEP)
?urinary M-protein excretion > 200 mg/24 hours
?Involved sFLC measurement > 10 mg/dL, provided that the sFLC ratio is abnormal (< 0.26 or > 1.65) as per IMWG response criteria.
Eastern Cooperative Oncology Group (ECOG) performance status of ? 2.
Life expectancy of at least 3 months as per investigator`s judgment at time of screening.
Hematological function without transfusion support (within 7 days from screening assessment) as follows:
•ANC ? 1.0 x 109/L (without growth factor support)
•platelet count ? 25 x 109/L (without transfusions)
•hemoglobin ? 7.0 g/dL (transfusions permitted no later than 48 hours before screening).
Renal function as follows:
• calculated or measured creatinine clearance ? 30 mL/min using the Cockcroft-Gault equation or via 24-hour urine collection with plasma and urine creatinine concentrations, respectively.
Hepatic function as follows:
•aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x upper limit of normal (ULN)
• total bilirubin (TBIL) < 1.5 x ULN (unless considered due to Gilbert’s syndrome).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 80

Exclusion Criteria

Disease Related:
Known central nervous system involvement by multiple myeloma.
Evidence of primary or secondary plasma cell leukemia at the time of screening.
Waldenstrom’s macroglobulinemia.
Unresolved toxicities from prior anticancer therapy.
Other Medical Conditions
History of other malignancy within the past 3 years, with the following exceptions:
•malignancy treated with curative intent and with no known active disease present for ? 1 year before enrollment and felt to be at low risk for recurrence by the treating physician
•adequately-treated non-melanoma skin cancer or lentigo maligna without evidence of disease
•adequately-treated cervical carcinoma in situ without evidence of disease
•breast ductal carcinoma in situ with full surgical resection (ie, negative margins) and without evidence of disease
•prostate cancer with a Gleason score < 6 with undetectable prostate specific antigen (PSA) over 12 months
•treated medullary or papillary thyroid cancer
•adequately-treated urothelial papillary noninvasive carcinoma or carcinoma in situ
•similar neoplastic conditions with an expectation of > 95% five-year disease-free survival
• see exclusion criterion 202 (Evidence of primary or secondary plasma cell leukemia at the time of screening) for exclusion of subjects with evidence of primary or secondary plasma cell leukemia at the time of screening.
Known history of amyloidosis.
Current or known history of autoimmune diseases requiring systemic treatment in past 5 years except vitiligo, resolved childhood asthma/atopy, or subjects with history of hypothyroidism after completing treatment for autoimmune thyroid disease, stable on hormone replacement therapy.
Clinically not-controlled chronic or ongoing infectious disease requiring treatment at the time of study day 1 or within the 14 days before study day 1
Symptomatic peripheral sensory or motor neuropathy of grade ? 3.
History or presence of clinically relevant central nervous system (CNS) pathology as uncontrolled epilepsy or seizure disorder, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, and psychosis.
Active hepatitis B and C based on the following results:
•Positive for hepatitis B surface antigen (HepBsAg) (indicative of chronic hepatitis B or recent acute hepatitis B).
•Negative HepBsAg and positive for hepatitis B core antibody: hepatitis B virus DNA by polymerase chain reaction (PCR) is necessary. Detectable hepatitis B virus DNA suggests occult hepatitis B.
•Positive Hepatitis C virus antibody (HepCAb): hepatitis C virus RNA by PCR is necessary. Detectable hepatitis C virus RNA suggests chronic hepatitis C.
Known or suspected HIV infection or subjects who are HIV seropositive.
Baseline ECG QTc > 470 msec (applying Fridericia correction), defined as the average of individual baseline ECGs.
Prior/Concomitant Therapy
Previously received an allogeneic stem cell transplant and the occurrence of 1 or more of the followin

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified