plasma cel myeloom Ziekte van Kahler
Conditions
Interventions
Infusion of AMG 701, (prolonged) hospitalization, blood samples, tumor biopsy
Sponsors
Amgen
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: • Age >= 18 years at the time of signing the informed consent • Multiple Myeloma meeting the following criteria: - Pathologically-documented diagnosis of multiple myeloma that has is relapsed after or is refractory (see section 12.14) as defined by the following: o Relapsed after >= 3 lines of prior therapy that must include all approved and available therapies deemed eligible by the investigator, including at a minimum of a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and where approved and available, a CD38-directed cytolytic antibody in combination in the same line or separate lines of treatment OR refractory to PI, IMiD and CD38-directed cytolytic antibody. o Note: Subjects enrolled in the phase 1b AMG 701 monotherapy dose-confirmation part, Group 2 must be relapsed or intolerant to BCMA targeting agent. - Measurable disease, defined by one or more of the following at time of screening: o a serum M protein > 0.5 g/dl measured by serum protein electrophoresis o urinary M protein excretion > 200 mg/24 hours o involved serum free light chain (sFLC) measurement > 10 mg/dl, provided that the sFLC ratio is abnormal ( 1.65) as per IMWG response criteria • ECOG Performance Status of = 1.0 x 109/L (without growth factor support) - platelet count >= 50 x 109/L (without transfusions within 7 days from screening assessment); platelet count between 25 and 50 x 109/L at time of enrollment requires agreement by both the Investigator and Amgen Medical Monitor of acceptability before enrollment can be approved - hemoglobin > 8 g/dL • 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 • Hepatic function as follows: - aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
Exclusion criteria
Exclusion criteria: • Known extramedullary relapse in the absence of any measurable medullary involvement (exception: this exclusion criteria only applies to phase 1a (dose escalation) study.) • Known central nervous system involvement by multiple myeloma • Previously received an allogeneic stem cell transplant and the occurrence of one or more of the following: - received the transplant within 6 months prior to study day 1 - received immunosuppressive therapy within the last 3 months prior to study day 1 - any active acute graft versus host disease (GvHD) requiring systemic therapy within the last 4 weeks prior to start of study treatment - any systemic therapy against GvHD within 4 weeks prior to start of IP treatment • Autologous stem cell transplantation less than 90 days prior to study day 1 • Recent history of primary plasma cell leukemia (within last 6 months prior to enrollment) or evidence of primary or secondary plasma cell leukemia at the time of screening • Waldenstrom*s macroglobulinemia • Prior amyloidosis (patients with multiple myeloma with asymptomatic deposition of amyloid plaques found on biopsy would be eligible if all othercriteria are met) • Treatment with systemic immune modulators including, but not limited to, nontopical systemic corticosteroids (unless the dose is 470 msec (applying Fridericia correction), defined as the average of individual baseline ECGs • History of malignancy other than multiple myeloma within the past 3 years with exceptions listed in the protocol section 6.2. • Current or known history of autoimmune diseases requiring systemic treatment in past 5 years, excluding autoimmune thyroid disease, for which treatment should be completed 6 months prior to enrollment. Refer to section 6.2 of the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase 1 - AMG 701 dose-exploration as monotherapy Primary Endpoint: -Dose limiting toxicities (DLTs), treatment-emergent adverse events, treatment-related adverse events -Clinically-significant changes in vital signs, physical examinations, electrocardiogram (ECG)s and clinical laboratory tests Phase 1b - AMG 701 dose-confirmation as monotherapy Primary Endpoint: -Dose-limiting toxicities (DLTs), treatment-emergent adverse events, treatment-related adverse events, and changes in vital signs, electrocardiograms (ECGs), and clinical laboratory tests Phase 1/1b - AMG 701 in combination with pomalidomide, with and without Dexamethasone (AMG 701-P±d) Primary Endpoint: -DLTs, treatment-emergent adverse events, treatment-related adverse events, disease related events -Clinically-significant changes in vital signs, physical examinations, ECGs, and clinical laboratory tests For more information, please refer to protocol section 4. | — |
Secondary
| Measure | Time frame |
|---|---|
| Phase 1 - AMG 701 dose-exploration as monotherapy Secondary Endpoints: * AMG 701 PK parameters including, but not limited to, maximum concentration (Cmax), time of maximum concentration (Tmax) and area under the concentration-time curve (AUC), and steady state concentration (Css) for extended IV. * Efficacy parameters: o Overall response (OR) according to International Myeloma Working Group (IMWG) response criteria, BOR of stringent CR [sCR], complete response [CR], very good partial response [VGPR], or partial response [PR]) Phase 1b - AMG 701 dose-confirmation as monotherapy Secondary Endpoints: * OR according to IMWG response criteria (BOR of sCR, CR, VGPR, or PR) Phase 1/1b - AMG 701 in combination with pomalidomide, with and without Dexamethasone (AMG 701-P±d) Secondary Endpoints: * AMG 701 PK parameters including, but not limited to: Cmax, Tmax, AUC, and Css for extended IV For more information, please refer to protocol section 4. | — |
Countries
Netherlands
Outcome results
None listed