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JOURNAL ONKOLOGIE – STUDIE

A Study to Evaluate the Effectiveness and Safety of CAEL-101 in Patients With Mayo Stage IIIb AL Amyloidosis

Rekrutierend

NCT-Nummer:
NCT04504825

Studienbeginn:
August 2020

Letztes Update:
06.01.2021

Wirkstoff:
CAEL-101, cyclophosphamide, bortezomib, and dexamethasone (CyBorD)

Indikation (Clinical Trials):
Immunoglobulin Light-chain Amyloidosis, Paraproteinemias, Amyloidosis

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
Caelum Biosciences

Collaborator:
IQVIA Biotech

Kontakt

Studienlocations (3 von 79)

Charité Universitätsmedizin Berlin (CBF)
12203 Berlin
(Berlin)
GermanyNoch nicht rekrutierend» Google-Maps
Heinrich-Heine-Universität Düsseldorf
40225 Düsseldorf
(Nordrhein-Westfalen)
GermanyNoch nicht rekrutierend» Google-Maps
Kinderonkologisches Zentrum Universitätsklinikum Essen
Hufelandstraße 55
45147 Essen
DeutschlandNoch nicht rekrutierend» Google-Maps
Hämatologisch-Onkologische Praxis Altona (HOPA)
22767 Hamburg
(Hamburg)
GermanyNoch nicht rekrutierend» Google-Maps
Universitätsklinikum Heidelberg
69120 Heidelberg
(Baden-Württemberg)
GermanyNoch nicht rekrutierend» Google-Maps
Medizinischen Klinik A Universitätsklinikum Münster
48149 Münster
(Nordrhein-Westfalen)
GermanyNoch nicht rekrutierend» Google-Maps
University Hospital Würzburg
97080 Würzburg
(Bayern)
GermanyNoch nicht rekrutierend» Google-Maps
Mayo Clinic - Arizona
85054 Scottsdale
United StatesNoch nicht rekrutierend» Google-Maps
City of Hope Medical Center
91010 Duarte
United StatesRekrutierend» Google-Maps
Stanford Amyloid Center
94305 Stanford
United StatesRekrutierend» Google-Maps
Colorado Blood Cancer Institute
80218 Denver
United StatesNoch nicht rekrutierend» Google-Maps
Mayo Clinic - Jacksonville
32224 Jacksonville
United StatesNoch nicht rekrutierend» Google-Maps
Loyola University Health System
60153 Maywood
United StatesNoch nicht rekrutierend» Google-Maps
Indiana University School of Medicine Amyloid Research and Treatment
46202 Indianapolis
United StatesRekrutierend» Google-Maps
Boston University Amyloidosis Center
02118 Boston
United StatesRekrutierend» Google-Maps
Dana-Farber Cancer Institute
02215 Boston
United StatesNoch nicht rekrutierend» Google-Maps
University of Michigan
48109 Ann Arbor
United StatesNoch nicht rekrutierend» Google-Maps
Karmanos Cancer Institute
48201 Detroit
United StatesRekrutierend» Google-Maps
Mayo Clinic - Rochester
55905 Rochester
United StatesNoch nicht rekrutierend» Google-Maps
Washington University School of Medicine
63110 Saint Louis
United StatesRekrutierend» Google-Maps
Columbia University Medical Center - Herbert Irving Pavillion
10032 New York
United StatesRekrutierend» Google-Maps
Weill Cornell Medical Center
10065 New York
United StatesNoch nicht rekrutierend» Google-Maps
University of Rochester- Wilmot Cancer Center
14642 Rochester
United StatesNoch nicht rekrutierend» Google-Maps
UNC Lineberger Comprehensive Cancer Center
27599-7295 Chapel Hill
United StatesNoch nicht rekrutierend» Google-Maps
Duke University
27705 Durham
United StatesNoch nicht rekrutierend» Google-Maps
Wake Forest Baptist Health
27157 Winston-Salem
United StatesNoch nicht rekrutierend» Google-Maps
Cleveland Clinic Amyloidosis Center
44195 Cleveland
United StatesRekrutierend» Google-Maps
The Ohio State University
43210 Columbus
United StatesRekrutierend» Google-Maps
Oregon Health & Science University
97239 Portland
United StatesNoch nicht rekrutierend» Google-Maps
Hospital of the University of Pennsylvania, Perelman Center for Advanced Medicine
19104 Philadelphia
United StatesRekrutierend» Google-Maps
Tennessee Oncology
37203-1625 Nashville
United StatesNoch nicht rekrutierend» Google-Maps
Vanderbilt University Medical Center
37232 Nashville
United StatesNoch nicht rekrutierend» Google-Maps
University of Texas Southwestern Medical Center
75390 Dallas
United StatesNoch nicht rekrutierend» Google-Maps
Houston Methodist Hospital
77030 Houston
United StatesNoch nicht rekrutierend» Google-Maps
The University of Texas MD Anderson Cancer Center
77030 Houston
United StatesRekrutierend» Google-Maps
University of Utah Huntsman Cancer Institute
84112 Salt Lake City
United StatesNoch nicht rekrutierend» Google-Maps
Seattle Cancer Care Alliance
98109 Seattle
United StatesRekrutierend» Google-Maps
Medical College of Wisconsin
53226 Milwaukee
United StatesNoch nicht rekrutierend» Google-Maps
Royal Adelaide Hospital
SA 5000 Adelaide
AustraliaNoch nicht rekrutierend» Google-Maps
Eastern Health (Box Hill Hospital)
VIC 3128 Box Hill
AustraliaNoch nicht rekrutierend» Google-Maps
Fiona Stanley Hospital
WA 6150 Murdoch
AustraliaNoch nicht rekrutierend» Google-Maps
Westmead Hospital
NSW 2145 Westmead
AustraliaNoch nicht rekrutierend» Google-Maps
Princess Alexandra Hospital
QLD 4102 Woolloongabba
AustraliaNoch nicht rekrutierend» Google-Maps
Universite Libre de Bruxelles (ULB) - Institut Jules Bordet
1000 Bruxelles
BelgiumNoch nicht rekrutierend» Google-Maps
Tom Baker Cancer Centre
T2N 4N2 Calgary
CanadaNoch nicht rekrutierend» Google-Maps
Cross Cancer Institute
T6G 1Z2 Edmonton
CanadaNoch nicht rekrutierend» Google-Maps
Princess Margaret Cancer Centre
M5G 2M9 Toronto
CanadaNoch nicht rekrutierend» Google-Maps
Hôpital Henri Mondor
94010 Créteil
FranceNoch nicht rekrutierend» Google-Maps
Hopital Claude Huriez
59037 Lille
FranceNoch nicht rekrutierend» Google-Maps
CHU Limoges National Refferral Center of Amyloidosis- AL Amyloidosis
87042 Limoges
FranceNoch nicht rekrutierend» Google-Maps
Institut Paoli Calmettes
13009 Marseille
FranceNoch nicht rekrutierend» Google-Maps
Assistance Publique - Hopitaux de Paris - Hopital Saint-Louis
75010 Paris
FranceNoch nicht rekrutierend» Google-Maps
Hospices Civils de Lyon (HCL) - Centre Hospitalier Lyon-Sud
69310 Pierre-Bénite
FranceNoch nicht rekrutierend» Google-Maps
CHU de Poitiers Néphrologie et transplantation rénale
86021 Poitiers
FranceNoch nicht rekrutierend» Google-Maps
Centre Hospitalier Universitaire (CHU) de Rennes - Hopital de Pontchaillou
35033 Rennes
FranceNoch nicht rekrutierend» Google-Maps
National and Kapodistrian University of Athens
11528 Athens
GreeceNoch nicht rekrutierend» Google-Maps
University General Hospital of Patras
26504 Patras
GreeceNoch nicht rekrutierend» Google-Maps
AHEPA University Hospital of Thessaloniki
546 36 Thessaloníki
GreeceNoch nicht rekrutierend» Google-Maps
Hadassah University Hospital - Ein Kerem
911200 Jerusalem
IsraelNoch nicht rekrutierend» Google-Maps
The Tel Aviv Sourasky Medical Center - Hematology Institute
Tel Aviv-Yafo
IsraelNoch nicht rekrutierend» Google-Maps
Universita degli Studi di Pavia - Fondazione IRCCS Policlinico San Matteo
27100 Pavia
ItalyNoch nicht rekrutierend» Google-Maps
Jikei University Kashiwa Hospital
277-8567 Chiba
JapanNoch nicht rekrutierend» Google-Maps
Fukushima Medical University School of Medicine
960-1295 Fukushima
JapanNoch nicht rekrutierend» Google-Maps
Kumamoto University Hospital
860-8556 Kumamoto
JapanNoch nicht rekrutierend» Google-Maps
Kyoto Kuramaguchi Medical Center
603-8151 Kyoto
JapanNoch nicht rekrutierend» Google-Maps
Nagoya City University Hospital
467-8602 Nagoya
JapanNoch nicht rekrutierend» Google-Maps
Japanese Red Cross Medical Center
150-8935 Tokyo
JapanNoch nicht rekrutierend» Google-Maps
Magodent Sp. z o.o, Szpital Elbląska, Oddział Onkologii Klinicznej i Chemiotera
01-748 Warszawa
PolandNoch nicht rekrutierend» Google-Maps
Pavlov State Medical University
197022 Petersburg
Russian FederationNoch nicht rekrutierend» Google-Maps
Almazov National Medical Research Center
197341 Saint Petersburg
Russian FederationNoch nicht rekrutierend» Google-Maps
Hospital Universitari Vall d'Hebron
08035 Barcelona
SpainNoch nicht rekrutierend» Google-Maps
Hospital Clinic de Barcelona
08036 Barcelona
SpainNoch nicht rekrutierend» Google-Maps
Programa de Amiloidosis Cardiaca Hospital Universitario Puerto de Hierro Majadah
28222 Madrid
SpainNoch nicht rekrutierend» Google-Maps
University of Navarra
31192 Pamplona
SpainNoch nicht rekrutierend» Google-Maps
University College London Hospital
NW1 2PG London
United KingdomNoch nicht rekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Detailed Description:

This is a double-blind, randomized, multicenter international Phase 3 study of CAEL-101

combined with the standard of care (SoC) for plasma cell dyscrasia (PCD) versus placebo

combined with standard of care PCD treatment in patients with Mayo stage IIIb AL amyloidosis

that have not received prior treatment. The minimum planned treatment time for each patient

will be at least 50 weeks or until the patient's death. It is planned that all patients will

continue their double-blind treatment until the last patient completes at least 50 weeks of

treatment.

Approximately 111 patients will be enrolled using a 2:1 randomization ratio of CAEL-101:

placebo and will involve approximately 70 investigator sites.

The primary objective of this study is to assess the effects of CAEL-101 versus placebo on

all-cause mortality.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Each patient must meet the following criteria to be enrolled in this study.

1. Provide written informed consent and be willing and able to comply with all study

procedures

2. Adult, 18 years and older

3. AL amyloidosis Mayo stage IIIb based on the 2013 European Modification of the

2004 Standard Mayo Clinic Staging in patients with advanced cardiac involvement

at the time of Screening

4. Measurable hematologic disease at Screening as defined by at least one of the

following:

1. Involved/Uninvolved Free Light Chain Difference (dFLC) > 4 mg/dL or

2. Involved Free Light Chain (iFLC) > 4 mg/dL with abnormal ratio or

3. Serum Protein Electrophoresis (SPEP) m-spike > 0.5 g/dL

5. Histopathological diagnosis of amyloidosis AND confirmation of AL derived amyloid

deposits by at least one of the following:

1. Immunohistochemistry or

2. Mass spectrometry or

3. Characteristic electron microscopy appearance

6. Cardiac involvement as defined by:

1. Documented clinical signs and symptoms supportive of a diagnosis of heart

failure in the setting of a confirmed diagnosis of AL amyloidosis in the

absence of an alternative explanation for heart failure AND

2. At least one of the following:

i. Endomyocardial biopsy demonstrating AL cardiac amyloidosis or

ii. Echocardiogram demonstrating a mean left ventricular wall thickness > 12 mm

at diastole in the absence of other causes (e.g., severe hypertension, aortic

stenosis), which would adequately explain the degree of wall thickening or

iii. Cardiac MRI with gadolinium contrast agent diagnostic or cardiac amyloidosis

7. Planned first-line treatment for plasma cell disorder is CyBorD administered as

Standard of Care (SoC)

8. Adequate bone marrow reserve and hepatic and renal function as demonstrated by:

1. Absolute neutrophil count ≥ 1.0 x 109/L

2. Platelet count ≥ 75 x 109/L

3. Hemoglobin ≥ 9 g/dL

4. Total direct bilirubin ≤ 2 times the upper limit of normal (x ULN) unless

due to Gilbert's syndrome.

5. Aspartate aminotransferase (AST) ≤ 3 x ULN

6. Alanine aminotransferase (ALT) ≤ 3 x ULN

7. Alkaline phosphatase (ALP) ≤ 5 x ULN (except for patients with hepatomegaly

and isozymes specific to liver, rather than bone)

8. Estimated glomerular filtration rate (eGFR) ≥ 15 mL/min

9. Women of childbearing potential (WOCBP) must have a negative pregnancy test

during Screening and must agree to use effective physician approved contraception

from Screening to 90 days following the last study drug administration

10. Men must be surgically sterile or must agree to use effective physician approved

contraception from Screening to 90 days following the last study drug

administration

Exclusion Criteria:

- Patients who meet any of the following criteria will not be permitted entry to the

study.

1. Have any other form of amyloidosis other than AL amyloidosis

2. Received prior therapy for AL amyloidosis or multiple myeloma. A maximum exposure

of 160 mg dexamethasone (or equivalent corticosteroid) since diagnosis of AL

amyloidosis and prior to randomization is allowed.

3. Meets the International Myeloma Working Group (IMWG) definition of multiple

myeloma or POEMS syndrome

4. Have supine systolic blood pressure < 90 mmHg or symptomatic orthostatic

hypotension, defined as a decrease in systolic blood pressure upon standing of >

30 mmHg despite medical management (e.g., midodrine, fludrocortisones) in the

absence of volume depletion

5. Taking prednisone or its equivalent > 10 mg/day

6. Taking doxycycline

7. Receiving dialysis

8. Planned stem cell transplant during the first 6 months of protocol therapy. Stem

cell collection during the protocol therapy is permitted.

9. Have had myocardial infarction, uncontrolled angina, severe uncontrolled

ventricular arrhythmias within 6 months prior to screening or percutaneous

cardiac intervention with recent stent or coronary artery bypass grafting within

4 months prior to screening

10. Left Ventricular Ejection Fraction (LVEF) is < 40% by echocardiogram at Screening

11. Have severe valvular stenosis (e.g., aortic or mitral stenosis with a valve area

< 1.0 cm2) or severe congenital heart disease

12. Have history of sustained ventricular tachycardia or aborted ventricular

fibrillation or a history of atrioventricular nodal or sinoatrial nodal

dysfunction for which a pacemaker/implantable cardioverter-defibrillator (ICD) is

indicated but not placed. (Participants who do have a pacemaker or ICD are

allowed in the study.)

13. QT corrected by Fridericia (QTcF) is > 550 msec. Participants who have a

pacemaker may be included regardless of calculated QTc interval.

14. There is evidence of acute ischemia or active conduction system abnormalities

with the exception of any of the following:

1. First degree Atrioventricular (AV)-block

2. Second degree AV-block Type 1 (Mobitz Type 1/Wenckebach type)

3. Right or left bundle branch block

4. Atrial fibrillation with a controlled ventricular rate. (An uncontrolled

ventricular rate [i.e., > 110 beats per minute] determined by an average of

three beats in lead II or representative beats in lead II is not allowed)

15. Have had major surgery within 4 weeks of randomization or is planning major

surgery during the study. Patients with surgical procedures conducted under local

anesthesia may participate

16. There is active malignancy (including lymphoma) with the exception of any of the

following:

1. Adequately treated basal cell carcinoma, squamous cell carcinoma, or in situ

cervical cancer

2. Adequately treated stage I cancer from which the patient is currently in

remission and has been in remission for > 2 years

3. Low-risk prostate cancer with Gleason score < 7 and prostate-specific

antigen < 10 mg/mL

4. Other localized and/or low risk malignancies may be permitted with Medical

Monitor approval.

17. Have received an investigational drug/device in another clinical investigational

study within 60 days before Screening

18. Women who are breast feeding

Studien-Rationale

Primary outcome:

1. Time from the first dose of study drug until death or end of study. (Time Frame - 50 weeks)

2. Number of patients with treatment emergent adverse events as assessed by CTCAE v5.0 (Time Frame - 50 weeks)

Secondary outcome:

1. Change in distance walked (in meters) during a six-minute walk test (Time Frame - 50 weeks)

2. Quality of Life (QOL) by the Kansas City Cardiomyopathy Questionnaire-Overall Score (KCCQ-OS) (Time Frame - 50 weeks):
A 23-item self-administered questionnaire that quantifies physical function, symptoms, social function, self-efficacy and knowledge and quality of life. It requires an average of 4-6 minutes to complete and uses an ordinal, adjectival (Likert) scale

3. Quality of Life (QOL) by the Short Form-36 (SF-36) v2 Physical Component Score (PCS) (Time Frame - 50 weeks):
A self-administered questionnaire containing 36 items that measures health on functional status, well-being and overall evaluation of health in 8 domains. It requires approximately 5 minutes to complete and uses scaled, ordinal responses (e.g., All of the time, Most of the time, A good bit of the time, etc.)

4. Cardiac Improvement by Global Longitudinal Strain (GLS%) (Time Frame - 50 weeks):
To assess improvement in heart function as measured by percent Global Longitudinal Strain (GLS%). GLS% is a non-invasive imaging technique to assess heart function where a higher/lower percentage is indicative of improvement.

Studien-Arme

  • Experimental: CAEL-101 combined with SoC plasma cell dyscrasia
    CAEL-101 is administered as an intravenous (IV) infusion over approximately 2 hours. The minimum planned treatment time for each patient will be at least 50 weeks or until the patient's death. It is planned that all patients will continue their double-blind treatment until the last patient completes at least 50 weeks of treatment. As this is an event driven study, the study will continue, and all patients will continue to receive study treatment until at least 54 deaths have been observed.
  • Placebo Comparator: Placebo combined with SoC plasma cell dyscrasia
    Patients randomized to receive placebo will receive 0.9% normal saline in an equivalent volume to a CAEL-101 infusion (approximately 250 cc). The minimum planned treatment time for each patient will be at least 50 weeks or until the patient's death. It is planned that all patients will continue their double-blind treatment until the last patient completes at least 50 weeks of treatment. As this is an event driven study, the study will continue, and all patients will continue to receive study treatment until at least 54 deaths have been observed.
  • Other: Concurrent Plasma Cell Dyscrasia Treatment
    All patients will also receive concurrent treatment for Plasma Cell Dyscrasia (PCD) with CyBorD according to institutional SoC. Patients should initiate their CyBorD chemotherapy regimen within 7 days of receiving the first dose of study drug. It is the intent of this protocol that patients will receive CyBorD per institution SoC in the study, as long as they are tolerating it. However, after two cycles of CyBorD, if the patient is not benefiting from or tolerating CyBorD in the Investigator's judgement, the investigator may change the CyBorD regimen or stop it.

Geprüfte Regime

  • CAEL-101:
    The investigational product, CAEL-101, is formulated as a sterile liquid solution of protein plus excipients for dilution in a single-use, stoppered, glass vial. Each 10 mL vial contains 300 mg of CAEL-101 at a concentration of 30 mg/mL. CAEL-101 will be diluted with commercially available 0.9% Normal Saline.
  • Placebo:
    Commercially available 0.9% Normal Saline will be used as the placebo.
  • cyclophosphamide, bortezomib, and Dexamethasone (CyBorD):
    According to institutional standard of care.

Quelle: ClinicalTrials.gov


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