Brief description of trial (Data source: BASEC)
In der Phase1b der Studie soll geprüft werden ob eine Behandlung mit AMG420 sicher und gut verträglich ist. Ausserdem, es wird die anti-Myelom Aktivität von AMG420 untersucht. Die Studie wird sich voraussichtlich über insgesamt etwa 6 Jahre erstrecken. Es wird damit gerechnet, dass insgesamt rund 22 Patienten an der Phase 1b der Studie teilnehmen werden.
Health conditions investigated(Data source: BASEC)
Rezidiviertes und/oder refraktäres multiples Myelom
Health conditions
(Data source: WHO)
Relapsed and/or Refractory Multiple Myeloma
Rare disease
(Data source: BASEC)
No
Intervention investigated (e.g. drug, therapy or campaign)
(Data source: BASEC)
AMG420 wird als i.v.-Infusionslösung in Infusionsbeuteln vorbereitet und über eine Infusionsleitung verabreicht. Die kontinuierliche Verabreichung der i.v.-Infusionslösung erfolgt über eine Pumpe, die der Patient über den gesamten 4-wöchigen Zeitraum der kontinuierlichen Infusion mit sich trägt. Die Gabe von AMG420 erfolgt in einer Dosierung von 600ug/Tag.
Interventions
(Data source: WHO)
Drug: AMG 420
Criteria for participation in trial
(Data source: BASEC)
Patienten mit einer pathologisch dokumentierten Diagnose von multiplem Myelom, die nach mindestens drei vorausgegangenen Behandlungslinien, einschliesslich eines Proteasom-Inhibitors, eines Immunmodulators und eines gegen CD38 gerichteten monoklonalen Antikörpers, ein Rezidiv erlitten haben oder gegenüber diesen Arzneimitteln refraktär sind, sind für diese Studie geeignet.
Die Krankheit muss ausserdem, zum Zeitpunkt des Screeinings, messbar sein, mit einem oder mehreren der folgenden Merkmale: Serum M-Protein > 0.5g/dl (gemessen durch Serumproteinelektophorese); Ausscheidung von M-Protein im Urin > 200mg/24 Stunden; Beteiligte sFLC Messung >10mg/dl, sofern das sFLC Verhältnis gemäss der IMWG-response Kriterien anormal ist (<0.26 oder >1.65).
Exclusion criteria
(Data source: BASEC)
Patienten, bei denen das multiple Myelom mit einer Beteiligung des Nervensystems einhergeht oder bei denen in den Voruntersuchungen eine primäre oder sekundäre Plasmazellleukämie festgestellt wird, oder die an Morbus Waldenström leiden, dürfen nicht an der Studie Teilnehmen.
Inclusion/Exclusion Criteria
(Data source: WHO)
Key Inclusion Criteria:
1. Subject has provided informed consent prior to initiation of any study specific
activities/procedures
2. Multiple myeloma meeting the following criteria:
3. Pathologically-documented diagnosis of multiple myeloma that is relapsed or is
refractory as defined by the following: Relapsed after 3 or more lines of prior
therapy that must include a proteasome inhibitors (PI), an immunomodulators (IMiD),
and a CD38-directed monoclonal antibody in any order during the course of treatment OR
refractory to a PI, IMiD, and CD38-directed monoclonal antibody.
-Measurable disease, defined by 1 or more of the following at time of screening: 1)
serum M-protein > 0.5 g/dL measured by serum protein electrophoresis (SPEP); 2)
urinary M-protein excretion > 200 mg/24 hours; 3) Involved serum free light chain
(sFLC ) measurement > 10 mg/dL, provided that the sFLC ratio is abnormal (<0.26 or
>1.65) as per IMWG response criteria
4. . ECOG performance status of less than or equal to 2
5. Life expectancy of at least 3 months per PI judgement at screening
6. Hematological function without transfusion support (within 7 days from screening
assessment) as follows:
- ANC = 1.0 x 10^9/L (without growth factor support)
- platelet count = 25 x 10^9/L (without transfusions)
- hemoglobin = 7.0 g/dL (transfusions permitted no later than 48 hours before
screening)
7. 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
8. Hepatic function as follows: AST and ALT < 3x upper limit of normal (ULN); TBIL <1.5 x
ULN (unless considered due to Gilbert's syndrome)
Key Exclusion Criteria:
1. Known central nervous system involvement by multiple myeloma
2. Evidence of primary or secondary plasma cell leukemia at the time of screening
3. Waldenstrom's macroglobulinemia
4. Unresolved toxicities from prior anticancer therapy, defined as not having resolved to
CTCAE version 5.0 grade 1 or to levels dictated in the eligibility criteria with the
exception of grade 2 peripheral neuropathy, alopecia, or toxicities from prior
anticancer therapy that are considered irreversible (defined as having been present
and stable for > 4 weeks) which may be allowed if they are not otherwise described in
the exclusion criteria and there is agreement to allow by the PI and Amgen medical
monitor
5. History of other malignancy within the past 3 years, with the following exceptions: 1.
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; 2. adequately-treated non-melanoma skin cancer or lentigo maligna without
evidence of disease; 3. adequately-treated cervical carcinoma in situ without evidence
of disease; 4. breast ductal carcinoma in situ with full surgical resection (ie,
negative margins) and without evidence of disease; 5. prostate cancer with a Gleason
score < 6 with undetectable PSA over 12 months; 6. treated medullary or papillary
thyroid cancer; 7. adequately-treated urothelial papillary noninvasive carcinoma or
carcinoma in situ; similar neoplastic conditions with an expectation of > 95%
five-year disease-free survival; 8. see exclusion criterion # 2 for exclusion of
subjects with evidence of primary or secondary plasma cell leukemia at the time of
screening
6. Known history of amyloidosis
7. 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.
8. 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
9. Symptomatic peripheral sensory or motor neuropathy of grade =3
10. 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
11. Active hepatitis B and C based on the following results: a) Positive for HepBsAg; b)
Negative HepBsAg and positive for hepatitis B core antibody; c) Positive Hepatitis C
virus antibody (HepCAb)
12. Known or suspected HIV infection or subjects who are HIV seropositive
13. Baseline ECG QTc > 470 msec (applying Fridericia correction)
14. Previously received an allogeneic stem cell transplant and the occurrence of 1 or more
of the following: a) received the transplant within 6 months prior to study day 1; b)
received immunosuppressive therapy within the last 3 months prior to study day 1; c)
any active acute graft versus host disease (GvHD), grade 2 to 4, according to the
Glucksberg criteria or active chronic GvHD requiring systemic treatment; d) any
systemic therapy against GvHD within 2 weeks prior to start of investigational product
treatment
15. Autologous stem cell transplantation < 90 days prior to study day 1
16. Treatment with systemic immune modulators including, but not limited to, nontopical
systemic corticosteroids (unless the dose is = 10 mg/day prednisone or equivalent),
cyclosporine, and tacrolimus within 2 weeks before study day 1
17. Last anticancer treatment < 2 weeks prior to study day 1
18. Last treatment with a therapeutic antibody less than 4 weeks prior to study day 1
19. Systemic radiation therapy within 28 days prior to study day 1. Focal radiotherapy
within 14 days prior to study day 1.
20. Major surgery defined as surgery requiring general anesthesia with endotracheal
intubation within 28 days prior to study day 1, unless discussed with and eligibility
approved by Amgen medical monitor
21. Prior treatment with any drug that specifically targets BCMA on tumor cells (eg, other
bi-specific antibody constructs, antibody drug conjugates, or CAR T-cells, except for
subjects who were previously treated with AMG 420 in this study and who are candidates
for second-course treatment
22. Treatment with medications known to cause QTc interval prolongation within the washout
periods described in Section 12.10 unless approved by the Amg
-
Further information on trial
Date trial registered
Feb 5, 2019
Incorporation of the first participant
Mar 4, 2019
Recruitment status
Completed
Academic title
(Data source: WHO)
A Phase 1b Multicenter, Open-label, Expansion Study to Assess the Safety and Efficacy of AMG 420 as Monotherapy in Subjects With Relapsed and/or Refractory Multiple Myeloma
Type of trial
(Data source: WHO)
Interventional
Design of the trial
(Data source: WHO)
Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
Phase
(Data source: WHO)
Phase 1
Primary end point
(Data source: WHO)
Subject incidence of dose-limiting toxicities;Subject incidence of treatment emergent adverse events;Subject incidence of treatment related adverse events;Subject incidence of changes in vital signs;Subject Incidence of Changes in ECGs;Subject incidence of Changes in clinical laboratory tests
Secundary end point
(Data source: WHO)
Overall Response Rate;Duration of Response;Minimal Residual Disease negativity at the time of CR;Half-life;Time to response;Clearance;Apparent Css;Progression Free Survival (PFS);Overall Survival;Best Overall Response;Treatment-free Interval
Contact information
(Data source: WHO)
Please refer to primary and secondary sponsors
Trial results
(Data source: WHO)
Results summary
no information available yet
Link to the results in the primary register
no information available yet
Information on the availability of individual participant data
no information available yet
Trial sites
Trial sites in Switzerland
(Data source: BASEC)
St. Gallen
Countries
(Data source: WHO)
Australia, Belgium, Japan, Switzerland, United States
Contact for further information on the trial
Details of contact in Switzerland
(Data source: BASEC)
Thomas Schwaller
+41 41 3692520
tschwall@amgen.com
Contact for general information
(Data source: WHO)
MD
Amgen
Contact for scientific information
(Data source: WHO)
MD
Amgen
Authorisation by the ethics committee (Data source: BASEC)
Name of the authorising ethics committee (for multicentre studies only the lead committee)
Ethikkommission Ostschweiz (EKOS)
Date of authorisation by the ethics committee
11.07.2019
Further trial identification numbers
Trial identification number of the ethics committee (BASEC-ID)
(Data source: BASEC)
2019-00553
Secondary ID (Data source: WHO)
20160370
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