HOVON HO150 AML

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Main info

Identifier:
HOVON 150 AML / AMLSG 29-18
Sponsor:
HOVON
Working group party:
Leukemia
Age:
>= 18
Stage:
1st Line
Echelon:
Level C-HIC&C-SCT
Included patients:
590
(of 968)
Active sites:
185
(of 219)
8 sites are pending
Title:

A phase 3, multicenter, double-blind, randomized, placebo-controlled study of ivosidenib or enasidenib in combination with induction therapy and consolidation therapy followed by maintenance therapy in patients with newly diagnosed acute myeloid leukemia or myelodysplastic syndrome with excess blasts-2, with an IDH1 or IDH2 mutation, respectively, eligible for intensive chemotherapy.

Timeline

Scheduled
Actual
2017
01 Mar
Opportunity
2017
01 Sep
Development
2018
01 Jan
Development
2018
30 Jul
Submission in Progress
2018
20 Sep
Submission in Progress
2018
15 Oct
Activated
2018
15 Oct
EC Approval
2018
01 Nov
First Site
2018
01 Dec
FPI
2019
01 Mar
EC Approval
2019
01 Mar
Activated
2019
19 Jun
First Site
2019
19 Jun
FPI
2024
15 Mar
ClosedForInclusionScheduledStart
2034
15 Mar
CloseoutInProgressLastPtOutScheduledStart
2035
15 Mar
Archived

News

News 02 June 2022: The IDH2 cohort accrual will reopen at 07 JUN 2022

11MAR2022 New lab manual
The new lab manual has been sent to all paricipating sites.

03 March 2022: Updated CRF instructions are available.

News 07APR2021: implementation Amendment 02
As of April 7th, 2021, Amendment 02 has been implemented. The following documents have been updated on the website:

  • Protocol v5, 15JUN2020
  • Protocol signature page, v5
  • Template ICF v4, 15JUN2020
  • Screening ICF, 09MAY2020
  • Statement of Expenses form
  • Pharmacy Manual, 31MAR2021
  • Lab Manual, 11FEB2021
  • REGRAND form, 25JUN2020

Update October 2019
The following documents have been updated after release:

  • Site lab manual (current date 01OCT2019), reason for update: further clarification on sending of samples.

Flow

Flow

Details

Phase:
Prospective double-blind randomized phase III study
Monitoring Type:
Study Specific
Objectives:

Primary study objective:

  • To compare event-free survival (EFS) between ivosidenib/enasidenib and placebo in combination with induction therapy and consolidation therapy followed by maintenance therapy in patients with newly diagnosed AML or MDS-EB2, with an IDH1 or IDH2 mutation, eligible for intensive chemotherapy.

Secondary study objectives:

  • Key secondary study objective:
    • To determine if treatment with ivosidenib/enasidenib, as compared to placebo prolongs overall survival (OS).
  • Other secondary study objectives:
    • To compare relapse-free survival (RFS), cumulative incidence of relapse (CIR) and cumulative incidence of death (CID) after CR/CRi between treatment including ivosidenib/enasidenib and treatment including placebo.
    • To evaluate minimal residual disease (MRD) status at sequential time points throughout treatment and CRMRD− rate between treatment including ivosidenib/enasidenib vs. placebo, using molecular and/or flow cytometric techniques.
    • To assess the safety and tolerability of treatment including ivosidenib/enasidenib vs. placebo by comparing the frequency and severity of adverse events according to CTCAE.
    • To compare complete remission (CR/CRi) rates for treatment including ivosidenib/enasidenib vs. placebo.
    • To assess the time to hematopoietic recovery (ANC 0.5 and 1.0x109/l; platelets 50 and 100x109/l) after each chemotherapy treatment cycle.
    • To determine quality of life (QoL) during maintenance treatment with ivosidenib/enasidenib vs. placebo.
  • Exploratory objective:
    • To study the pharmacokinetics of treatment including ivosidenib/enasidenib in a small subset of patients.

See protocol section 13 for endpoint definitions and appendices B and C for definitions of response criteria and outcome measures.

Eligibility

Inclusion Criteria:
  • Age ≥18 years
  • Newly diagnosed AML or MDS-EB2 defined according to WHO criteria, with a documented IDH1 or IDH2 gene mutation (as determined by the clinical trial assay) at a specific site (IDH1 R132, IDH2 R140, IDH2 R172). AML may be secondary to prior hematological disorders, including MDS, and/or therapy-related (in which prior disease should have been documented to have existed for at least 3 months). Patients may have had previous treatment with hypomethylating agents (HMAs) for MDS. HMAs have to be stopped at least four weeks before registration
  • Patients with dual mutant FLT3 and IDH1 or IDH2 mutations may be enrolled only if, for medical or other reasons, treatment with a FLT3 inhibitor is not considered.
  • Considered to be eligible for intensive chemotherapy.
  • ECOG/WHO performance status ≤ 2
  • Adequate hepatic function as evidenced by:
    • Serum total bilirubin ≤ 2.5 × upper limit of normal (ULN) unless considered due to Gilbert’s disease (e.g. a mutation in UGT1A1) (only for patients in IDH2 cohort), or leukemic involvement of the liver – following written approval by the (Co)Principal Investigator.
    • Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤ 3.0 × ULN, unless considered due to leukemic involvement of the liver, following written approval by the Principal Investigator.
  • Adequate renal function as evidenced by creatinine clearance > 40 mL/min based on the Cockroft-Gault formula for glomerular filtration rate (GFR).
  • Able to understand and willing to sign an informed consent form (ICF).
  • Written informed consent
  • Female patient must either:
    • Be of nonchildbearing potential:
      • Postmenopausal (defined as at least 1 year without any menses) prior to screening, or
      • Documented surgically sterile or status posthysterectomy (at least 1 month prior to screening)
    • Or, if of childbearing potential,
      • Agree not to try to become pregnant during the study and for 6 months after the final study drug administration
      • And have a negative urine or serum pregnancy test at screening
      • And, if heterosexually active, agree to consistently use highly effective* contraception per locally accepted standards in addition to a barrier method starting at screening and throughout the study period and for 6 months after the final study drug administration.

Highly effective forms of birth control include:

  • Consistent and correct usage of established hormonal contraceptives that inhibit ovulation,
  • Established intrauterine device (IUD) or intrauterine system (IUS),
  • Bilateral tubal occlusion,
  • Vasectomy (A vasectomy is a highly effective contraception method provided the absence of sperm has been confirmed. If not, an additional highly effective method of contraception should be used.)
  • Male is sterile due to a bilateral orchiectomy.
  • Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual activity during the entire period of risk associated with the study drug. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient.

List is not all inclusive. Prior to enrollment, the investigator is responsible for confirming patient will utilize highly effective forms of birth control per the requirements of the CTFG Guidance document ‘Recommendations related to contraception and pregnancy testing in clinical trials’, September 2014 (and any updates thereof) during the protocol defined period.

  • Female patient must agree not to breastfeed starting at screening and throughout the study period, and for 2 months and 1 week after the final study drug administration.
    • Female patient must not donate ova starting at screening and throughout the study period, and for 6 months after the final study drug administration.
  • Male patient and their female partners who are of childbearing potential must be using highly effective contraception per locally accepted standards in addition to a barrier method starting at screening and continue throughout the study period and for 4 months and 1 week after the final study drug administration
  • Male patient must not donate sperm starting at screening and throughout the study period and for 4 months and 1 week after the final study drug administration.
  • Subject agrees not to participate in another interventional study while on treatment.
Exclusion Criteria:
  • Prior chemotherapy for AML or MDS-EB2 (with the exception of HMA). Hydroxyurea is allowed for the control of peripheral leukemic blasts in patients with leukocytosis (e.g., white blood cell [WBC] counts > 30x109/L).
  • Dual IDH1 and IDH2 mutations.
  • Acute promyelocytic leukemia (APL) with PML-RARA or one of the other pathognomonic variant fusion genes/chromosome translocations.
  • Blast crisis after chronic myeloid leukemia (CML).
  • Known allergy or suspected hypersensitivity to Ivosidenib or Enasidenib and/or any exipients.
  • Taking medications with narrow therapeutic windows with potential interaction with investigational medication (see protocol Appendix I), unless the patient can be transferred to other medications prior to enrolling or unless the medications can be properly monitored during the study.
  • Taking P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) transporter-sensitive substrate medications (see protocol Appendix J) unless the patient can be transferred to other medications within ≥ 5 half-lives prior to administration of ivosidenib or enasidenib, or unless the medications can be properly monitored during the study.
  • Breast feeding at the start of study treatment.
  • Active infection, including hepatitis B or C or HIV infection that is uncontrolled at randomization. An infection controlled with an approved or closely monitored antibiotic/antiviral/antifungal treatment is allowed.
  • Patients with a currently active second malignancy. Patients are not considered to have a currently active malignancy if they have completed therapy and are considered by their physician to be at < 30% risk of relapse within one year. However, patients with the following history/concurrent conditions are allowed:
    • Basal or squamous cell carcinoma of the skin
    • Carcinoma in situ of the cervix
    • Carcinoma in situ of the breast
    • Incidental histologic finding of prostate cancer
  • Significant active cardiac disease within 6 months prior to the start of study treatment, including New York Heart Association (NYHA) Class III or IV congestive heart failure (protocol appendix G); myocardial infarction, unstable angina and/or stroke; or left ventricular ejection fraction (LVEF) < 40% by ultrasound or MUGA scan obtained within 28 days prior to the start of study treatment.
  • QTc interval using Fridericia’s formula (QTcF) ≥ 450 msec or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, family history of long QT interval syndrome). Prolonged QTc interval associated with bundle branch block or pacemaking is permitted with written approval of the (co) Principal Investigator.
  • Taking medications that are known to prolong the QT interval (see Appendix K), unless deemed critical and without a suitable alternative. In those cases, they may be administered, but with proper monitoring (see section 10.2, Table 13).
  • Dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of orally administered drugs.
  • Clinical symptoms suggestive of active central nervous system (CNS) leukemia or known CNS leukemia. Evaluation of cerebrospinal fluid (CSF) during screening is only required if there is a clinical suspicion of CNS involvement by leukemia during screening.
  • A known medical history of progressive multifocal leukoencephalopathy (PML).
  • Immediately life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or severe disseminated intravascular coagulation
  • Any other medical condition deemed by the Investigator to be likely to interfere with a patient’s ability to give informed consent or participate in the study.
  • Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

Registration Details

  • Patients who are possibly eligible for this trial should first be screened to determine the IDH1/2 mutation status. This can only be done after the patient has provided a written informed consent for the screening. Screening is done through a separate screening database. There are two screening databases for this trial, one managed by HOVON and one managed by AMLSG. Each group/institute that is participating in this trial is assigned one of the two screening databases.
  • Eligible patients should be registered before start of treatment. Patients need to be registered at the HOVON Data Center by one of the following options:
  • By ALEA; Use goto eCRF button > select the [Patient tab] and click the [Add new patient] button. Complete all items and click the [Submit] button
  • By faxing the completed registration/randomization CRF +31 (0)10 704 1028 Monday through Friday, from 09:00 to 17:00 CET
  • By phone +31 (0)10 704 1560 Monday through Friday, from 09:00 to 17:00 CET

The first Interim Analysis will be performed when the first 50 patients have either completed two cycles of induction therapy or discontinued the induction treatment.

Go to eCRF

Participating Sites

Ziekenhuizen die deelnemen aan het onderzoek staan benoemd op de HOVON website bij het onderzoek. Het kan zijn dat uw ziekenhuis niet genoemd wordt, maar wel aan het onderzoek deelneemt. Informeer hiernaar bij uw arts.

Site
193 results
Order by
Accrual rate
Activation date
DE-Ulm-UNIKLINKULM
37
27 May 2020
FR-Toulouse-CHUTOULOUSE
26
03 Jun 2020
FR-Pessac Cedex-CHUBORDEAUX
18
06 May 2020
NO-Oslo-OSLOUH
17
04 Sep 2020
NL-Rotterdam-ERASMUSMC
16
09 May 2019
LT-Vilnius-SANTA
15
28 Aug 2019
CH-Zürich-USZ
12
30 Dec 2019
FR-Rouen cedex-BECQUEREL
11
18 May 2020
NL-Amsterdam-VUMC
11
29 Apr 2019
DE-Oldenburg-KLINIKUMOLDENBURG
11
26 Oct 2020
FR-Marseille-IPC
10
14 Oct 2020
FR-Nantes-CHUNANTES
10
23 Jun 2020
CH-Bern-INSEL
10
09 Jan 2020
FR-Grenoble cedex 9-CHUGRENOBLE
8
28 Jul 2020
FR-Villejuif-GUSTAVEROUSSY
8
21 Jul 2020
NL-Zwolle-ISALA
8
18 Oct 2019
FR-Rennes cedex 9-CHURENNES
8
25 Mar 2020
CH-St. Gallen-KSSG
8
18 Dec 2019
FR-Nice-CAL
7
28 Apr 2020
FR-Lille-CHULILLE
7
23 Jun 2020
FR-Clamart-HIAPERCY
7
18 Jun 2020
NL-Groningen-UMCG
7
30 Dec 2019
FI-Helsinki-HUS
7
15 Apr 2020
NL-Amsterdam-AMC
7
28 Nov 2019
NL-Breda-AMPHIA
7
05 Sep 2019
BE-Haine-Saint-Paul-JOLIMONT
6
29 Jul 2020
CH-Basel-USB
6
08 Jan 2020
DE-Mainz-UNIMEDIZINMAINZ
6
18 Mar 2021
FR-Paris cedex 10-SAINTLOUIS
6
24 Jun 2020
FR-Bayonne-CHCOTEBASQUE
6
29 Jan 2021
CH-Bellinzona-IOSI
5
15 Jan 2020
FR-Lyon-LEONBERARD
5
11 Nov 2020
DE-Minden-MUEHLENKREISKLINKEN
5
29 Jul 2021
NL-Den Haag-HAGA
5
10 Dec 2019
BE-Yvoir-MONTGODINNE
5
30 Jun 2020
FR-Lyon Pierre Benite cedex-LYONSUD
5
02 Apr 2020
NL-Dordrecht-ASZ
5
18 Sep 2019
NL-Amsterdam-OLVG
5
04 Nov 2019
NL-Eindhoven-MAXIMAMC
5
11 Nov 2019
FR-Limoges-CHULIMOGES
4
23 Jun 2020
AU-Sydney-CONCORD
4
04 Nov 2020
DE-Braunschweig-KLINIKUMBRAUNSCHWEIG
4
28 Jun 2021
AU-Melbourne-RMELBOURNE
4
16 Oct 2020
AU-Douglas-TOWNSVILLE
4
14 Oct 2020
AU-Brisbane-PAH
4
05 Aug 2020
FR-Amiens-CHUAMIENS
4
21 Aug 2020
FR-Strasbourg cedex-HAUTEPIERRE
4
15 Sep 2020
ES-Barcelona-ICODURANREYNALS
4
27 Sep 2021
NL-Enschede-MST
4
31 Jul 2020
NL-Utrecht-UMCUTRECHT
4
10 Aug 2019
NL-Maastricht-MUMC
3
16 Dec 2019
NL-Amersfoort-MEANDERMC
3
28 Aug 2019
DE-Düsseldorf-MEDUNIDUESSELDORF
3
02 Dec 2020
DE-Bonn-UNIBONN
3
22 Jan 2021
NL-Arnhem-RIJNSTATE
3
26 Nov 2019
FR-Angers-CHUANGERS
3
11 Jun 2020
NL-Leiden-LUMC
3
02 Mar 2020
DE-Essen-KEM
3
17 Nov 2020
DE-Lemgo-KLINIKUMLIPPE
3
15 Mar 2021
FR-Vandoeuvre Les Nancy-CHRUNANCY
3
03 Jun 2020
DE-Flensburg-MALTESER
3
21 Oct 2020
FR-Le Chesnay cedex-CHVERSAILLES
3
05 Aug 2020
DE-Bochum-RUB
3
15 Dec 2020
FR-Tours cedex-BRETONNEAU
3
17 Feb 2021
FR-Créteil cedex-CHUMONDOR
3
08 Sep 2020
BE-Roeselare-AZDELTA
3
03 Jun 2020
AU-Perth-FSH
3
07 Aug 2020
DE-München-IRZTUM
3
12 Aug 2021
DE-Hannover-MHHANNOVER
3
02 Aug 2021
CH-Geneve (14)-HCUGE
3
04 Feb 2020
CH-Luzern-LUKS
3
19 Dec 2019
FR-Clermont Ferrand-ESTAING
3
27 May 2021
DE-Homburg-UNIKLINIKSAARLAND
3
10 Feb 2021
ES-Barcelona-SANTPAU
3
21 Jun 2021
DE-Hamburg-UKE
3
01 Sep 2021
FR-Paris cedex 12-SAINTANTOINE
3
23 Jul 2020
SE-Lund-SUH
3
09 Apr 2021
FR-Bobigny-AVICENNE
2
18 Jun 2020
AU-Camperdown-RPA
2
05 Nov 2020
BE-Brussel-UZBRUSSEL
2
15 Dec 2020
DE-Magdeburg-OVGU
2
01 Mar 2021
SE-Stockholm-KAROLINSKAHUDDINGE
2
12 Jan 2021
AU-Sydney-RNSH
2
24 Dec 2020
AT-Vienna-HANUSCH
2
29 Oct 2021
AU-Melbourne-ALFRED
2
19 Oct 2020
DE-Hamburg-ASKLEPIOSSTGEORG
2
04 Mar 2021
DE-Berlin-CAMPUSVIRCHOW
2
25 Aug 2021
DE-Meschede-HOCHSAUERLAND
2
16 Oct 2020
EE-Tartu-TARTU
2
05 Jun 2020
DE-Bad Saarow-HELIOSBADSAAROW
2
18 May 2021
FR-Besançon Cedex-JEANMINJOZ
2
04 Mar 2021
DE-Villingen-Schwenningen-SBKVS
2
18 May 2021
DE-Herne-MARIENHOSPITALHERNE
2
19 Feb 2021
FR-Nice-LARCHET
2
03 Mar 2020
FR-Paris cedex 15-NECKER
2
04 Jun 2020
NO-Tromsø-NORTHNOORWEGEN
2
16 Oct 2020
DE-Offenburg-ORTENAUKLINIKUM
2
03 Nov 2020
ES-Girona-ICSTRUETA
2
10 Aug 2021
DE-Karlsruhe-KLINIKUMKARLSRUHE
2
14 Jan 2021
DE-Passau-KLINIKUMPASSAU
2
16 Feb 2021
NL-Nieuwegein-ANTONIUS
2
16 Aug 2019
DE-Hannover-SILOAHKRH
2
16 Dec 2020
BE-Leuven-UZLEUVEN
2
02 Nov 2020
BE-Gent-UZGENT
2
11 Nov 2020
BE-Brugge-AZBRUGGE
2
25 May 2021
NL-Den Bosch-JBZ
2
18 Sep 2019
NL-Leeuwarden-MCL
2
23 Dec 2019
DE-Stuttgart-DIAKSTUTTGART
2
11 Nov 2020
IE-Dublin 8-STJAMES
2
02 Apr 2021
NL-Nijmegen-RADBOUDUMC
1
02 Sep 2019
DE-Hamburg-ASKLEPIOS
1
26 Jan 2021
SE-Uppsala-UPPSALAUH
1
02 Mar 2020
AU-Sydney-WSAH
1
01 Feb 2021
NL-Delft-RDGG
1
16 Dec 2019
DE-Ludwigshafen-KLILU
1
08 Jun 2021
DE-Aschaffenburg-KLINIKUMAB
1
16 Nov 2021
BE-Liege-CHULIEGE
1
19 Aug 2020
DE-Goch-KKLE
1
28 Apr 2021
AU-Adelaide-RAH
1
13 Nov 2020
NO-Trondheim-STOLAV
1
26 Oct 2020
ES-Barcelona-CLINICUB
1
18 Oct 2021
ES-Barcelona-MUTUATERRASSA
1
15 Nov 2021
FR-Chambery-CHMETROPOLESAVOIE
1
09 Jun 2020
NO-Bergen-HELSEBERGEN
1
21 Oct 2020
AU-Melbourne-SVHM
1
26 Oct 2020
AU-Perth-SCGH
1
20 Aug 2021
ES-Valencia-MALVARROSA
1
16 Feb 2022
AU-Adelaide-FLINDERS
1
29 Jan 2021
BE-Hasselt-VIRGAJESSE
1
09 Aug 2021
DE-Berlin-CAMPUSBENFRANKLIN
1
25 Aug 2021
DE-Darmstadt-KLINIKUMDARMSTADT
1
16 Aug 2021
IE-Cork-CUH
1
14 Jul 2021
CH-Fribourg-HFR
1
05 Dec 2019
AU-Perth-RPH
1
01 Dec 2021
IE-Galway-UHGALWAY
1
14 Mar 2022
AU-Waratah-CALVARYMATER
1
16 Nov 2021
AU-Launceston TAS-LAUNCESTON
1
21 Dec 2021
DE-Bremen-KBM
1
06 Apr 2021
DE-Hamm-EVKHAMM
1
26 Jul 2021
DE-Tübingen-MEDUNITUEBINGEN
1
23 Jun 2021
FR-Reims-CHREIMS
1
19 May 2021
DE-Berlin-CAMPUSMITTE
1
13 Apr 2022
DK-Aarhus N-AUH
DK-Aalborg-AALBORGUH
CH-Lausanne-CHUV
14 Apr 2020
CH-Aarau-KSA
BE-Brussel-BORDET
08 Dec 2020
AT-Linz-KEPLER
DE-Frankfurt-KLINIKUMFRANKFURT
18 Mar 2022
FR-Lens-CHLENS
01 Apr 2020
BE-Bruxelles-STLUC
29 Jun 2020
BE-Liege-CHRCITADELLE
11 May 2021
DE-Göttingen-MEDUNIGOETTINGEN
16 Feb 2022
AT-Salzburg-SALK
18 Nov 2021
BE-Antwerpen-ZNASTUIVENBERG
19 May 2020
LU-Luxembourg-CHL
27 Oct 2021
DE-Saarlouis-MARIENSAARLOUIS
DE-Berlin-VIVANTESNEUKOLLN
22 Jan 2021
DE-Berlin-VIVANTESURBAN
11 Oct 2021
DE-Dortmund-JOHODORTMUND
18 Dec 2020
DE-Düsseldorf-MARIENLDUSSELDORF
23 May 2022
DK-Odense-OUH
DK-Copenhagen-RIGSHOSPITALET
FR-Mulhouse-GHRMSA
11 Feb 2021
DE-Traunstein-TSSOB
21 Oct 2020
DE-Hanau-KLINIKUMHANAU
19 Nov 2021
ES-Barcelona-PARCDESALUTMAR
11 Oct 2021
DE-Lübeck-UKSHLUBECK
22 Dec 2021
ES-Barcelona-VHEBRON
30 Dec 2021
DE-Esslingen-KLINIKUMESSLINGEN
18 Mar 2021
ES-Lleida-ICSVILANOVA
08 Aug 2022
ES-Tarragona-JOAN
27 Oct 2021
FR-Argenteuil-CHARGENTEUIL
01 Jul 2020
FR-Poitiers-CHUPOITERS
09 Jul 2020
DE-Wuppertal-HELIOSGESUNDHEIT
07 Jan 2022
IE-Dublin 9-BEAUMONT
01 Apr 2021
FR-Montpellier-STELOI
29 Jun 2021
FR-Orléans-CHORLEANS
23 Feb 2021
ES-Barcelona-GERMANTRIALS
30 Jun 2021
ES-Madrid-CSGREGORIOMARANON
22 Dec 2021
FI-Tampere-TAYS
24 Jun 2021
ES-Palma-HSLL
DE-Trier-MUTTERHAUS
08 Apr 2022
AT-Linz-ORDENSKLINIKUM
07 Feb 2022
NO-Stavanger-HELSESTAVANGER
27 Oct 2020
DE-Kaiserslautern-WESTPFALZ
15 Jun 2022
AU-Melbourne-MONASH
26 Jul 2021
AU-Melbourne-AUSTIN
18 Nov 2020
AU-Hobart TAS-RHOBART
26 Oct 2020
DE-Giessen-UKGM
03 Feb 2022
DE-Luedenscheid-KLINIKUMLUEDENSCHEID
19 Jan 2021
ES-Palma-SSIB
08 Jul 2021
DE-Heilbronn-SLK
08 Jul 2021
= Active hospitals
= Inactive hospitals

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