Trial on the Effect of Isatuximab to Lenalidomide/Bortezomib/Dexamethasone (RVd) Induction and Lenalidomide Maintenance in Patients With Newly Diagnosed Myeloma (GMMG HD7)

Phase 3

Active, not recruiting

• Conditions: Multiple Myeloma
• Interventions: Drug: Lenalidomide; Drug: Bortezomib; Drug: Dexamethasone; Drug: Isatuximab

• Registration Number: NCT03617731
• Lead Sponsor: University of Heidelberg Medical Center

Brief Summary

Trial in patients with newly diagnosed myeloma to evaluate the effect of isatuximab in induction therapy with lenalidomide/bortezomib/dexamethasone (RVd) and in lenalidomide maintenance treatment

Detailed Description

Prospective, multicentre, randomised, parallel group, open, phase III clinical trial, for patients with confirmed diagnosis of untreated multiple myeloma requiring systemic therapy.

Investigational Medicinal Products: Isatuximab, Lenalidomide

1. Randomization: Patients are randomized in one of 2 study arms (IA or IB) before induction therapy. Patients randomized in arm IA will receive 3 cycles RVd (Bortezomib (Velcade®), Lenalidomide (Revlimid®, each cycle is 42 days), Dexamethasone). Patients in arm IB will additionally receive the monoclonal antibody Isatuximab in the 3 cycles RVd. After induction therapy patients undergo intensifying therapy according to GMMG standard (usually mobilization therapy followed by stem cell collection and autologous stem cell transplantation).

2. Randomization: Before maintenance treatment patients are randomized in one of 2 study arms (IIA and IIB): Patients in arm IIA receive Lenalidomide maintenance therapy for three years, patients in arm IIB receive additional Isatuximab.

There are two primary objectives:

1. to compare the induction regimen (IA vs IB) regarding minimal residual disease (MRD) negativity after induction (assessed by flow cytometry; sensitivity at least 1e-5)

2. to compare the maintenance strategies (arms IIA vs IIB) regarding progression-free survival (PFS), defined as time from 2nd randomization (prior to maintenance therapy) to progression or death from any cause whichever occurs first.

The duration of the trial for each patients is expected to be 45-48 months (induction and intensification treatment: 6-9 months, 3 months rest between intensification and start of maintenance phase 36 months).

Study Timeline

• Study First Submitted: 2018-07-24
• Study First Submitted QC: 2018-07-31
• Study First Posted: 2018-08-06
• Study Start: 2018-10-18
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-11
• Last Update Posted: 2023-05-12
• Primary Completion: 2025-05
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 662

Inclusion Criteria

1. Confirmed diagnosis of untreated multiple myeloma requiring systemic therapy (diagnostic criteria (IMWG updated criteria (2014)1) see appendix IA. For some patients systemic therapy may be required though these diagnostic criteria are not fulfilled. In this case the GMMG study office has to be consulted prior to inclusion.)

2. Patient is eligible for high dose therapy and autologous stem cell transplantation.

3. Measurable disease, defined as any quantifiable monoclonal protein value, defined by at least one of the following three measurements:2

   • Serum M-protein ≥ 10g/l (for IgA ≥ 5g/l)
   • Urine light-chain (M-protein) of ≥ 200 mg/24 hours
   • Serum FLC assay: involved FLC level ≥ 10 mg/dl provided sFLC ratio is abnormal

4. Age 18 - 70 years inclusive

5. WHO performance status 0-2

6. Negative pregnancy test at inclusion (females of childbearing potential)

7. All patients must agree on the requirements regarding the lenalidomide pregnancy prevention plan described in section 6. For all men and females of childbearing potential: patients must be willing and capable to use adequate contraception during the complete therapy.

8. All patients must

   • agree to abstain from donating blood while taking lenalidomide and for 28 days following discontinuation of lenalidomide therapy
   • agree not to share study drug lenalidomide with another person and to return all unused study drug to the investigator or pharmacist

9. Ability of patient to understand character and individual consequences of the clinical trial

10. Provide written informed consent (must be available before enrolment in the trial)

Exclusion Criteria

1. Patient has known hypersensitivity (or contraindication) to dexamethasone, sucrose histidine (as base and hydrochloride salt), boron, mannitol, and polysorbate 80 or any of the components of study therapy that are not amenable to premedication with steroids or H2 blockers that would prohibit further treatment with these agents.
2. Systemic AL amyloidosis (except for AL amyloidosis of the skin or the bone marrow)
3. Plasma cell leukemia
4. Previous chemotherapy or radiotherapy during the past 5 years except local radiotherapy in case of local myeloma progression. (Note: patients may have received a cumulative dose of up to 160 mg of dexamethasone or equivalent as emergency therapy.) Previous therapy due to smouldering myeloma may be acceptable. In this case the GMMG study office has to be consulted prior to inclusion
5. Severe cardiac dysfunction (NYHA classification III-IV), ejection fraction < 40%
6. Significant hepatic dysfunction (ASAT and/or ALAT ≥ 3 times normal level and/or serum bilirubin ≥ 1.5 times normal level if not due to hereditary abnormalities as Gilbert's disease), unless related to myeloma.
7. Patients with active or history of hepatitis B or C
8. HIV positivity
9. Patients with active, uncontrolled infections
10. Patients with severe renal insufficiency (Creatinine Clearance < 30ml/min)
11. Patients with peripheral neuropathy or neuropathic pain, CTC grade 2 or higher (as defined by the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0)
12. Patients with a history of active malignancy during the past 5 years with the exception of following malignancies after curative therapy: basal cell carcinoma of the skin, squamous cell skin carcinoma, stage 0 cervical carcinoma or any in situ malignancy
13. Patients with acute diffuse infiltrative pulmonary and/or pericardial disease
14. Autoimmune hemolytic anemia with positive Coombs test or immune thrombocytopenia
15. Platelet count < 75 x 109/l
16. Haemoglobin < 8.0 g/dl, unless related to myeloma
17. Absolute neutrophil count (ANC) < 1.0 x 109/l (the use of colony stimulating factors within 14 days before the test is not allowed)
18. Corrected serum calcium > 14 mg/dl (> 3.5 mmol/l)
19. Unable or unwilling to undergo thromboprophylaxis
20. Pregnancy and lactation
21. Participation in other clinical trials. This does not include long-term follow-up periods without active drug treatment of previous studies during the last 6 months.
22. Prisoners or subjects who are legally institutionalized, or those unwilling or unable to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions.

No patients will be allowed to enrol in this trial more than once.

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
IB	Dexamethasone	Patients in arm IB are treated with 3 cycles RVd + Isatuximab (lenalidomide 25 mg/d p.o. d1 - 14 and d22 - 35; bortezomib 1.3 mg/m2 s.c. d1, 4, 8, 11, 22, 25, 29, 32;dexamethasone p.o. 20 mg/d d1-2, 4-5, 8-9, 11-12, 15, 22-23, 25-26, 29-30, 32-33).Isatuximab (10 mg/kg i.v. C1: d 1, 8, 15, 22, 29; C2-3: d 1, 15, 29).Treatment repeats every 42 days (d43 = cycle 2 d1). Standard intensification: For all patients, stem cells are mobilized by GMMG Standard protocols (CAD: cyclophosphamide, doxorubicin, dexamethasone) and G-CSF. At least 7.5x106 CD34+ cells/kg body weight are harvested. High dose treatment (melphalan 200mg/m², HDT) followed by autologous stem cell transplantation (ASCT) is started 4 - 6 weeks after CAD. For patients not in CR after HDT1, a second HDT is performed within 3 months.
IA	Lenalidomide	Patients in arm IA are treated with 3 cycles RVd (lenalidomide 25 mg/d p.o. d1 - 14 and d22 - 35; bortezomib 1.3 mg/m2 s.c. d1, 4, 8, 11, 22, 25, 29, 32; dexamethasone p.o. 20 mg/d d1-2, 4-5, 8-9, 11-12, 15, 22-23, 25-26, 29-30, 32-33).Treatment repeats every 42 days (d43 = cycle 2 d1). Standard intensification: For all patients, stem cells are mobilized by GMMG Standard protocols (CAD: cyclophosphamide, doxorubicin, dexamethasone) and G-CSF. At least 7.5x106 CD34+ cells/kg body weight are harvested. High dose treatment (melphalan 200mg/m², HDT) followed by autologous stem cell transplantation (ASCT) is started 4 - 6 weeks after CAD. For patients not in CR after HDT1, a second HDT is performed within 3 months.
IA	Bortezomib	Patients in arm IA are treated with 3 cycles RVd (lenalidomide 25 mg/d p.o. d1 - 14 and d22 - 35; bortezomib 1.3 mg/m2 s.c. d1, 4, 8, 11, 22, 25, 29, 32; dexamethasone p.o. 20 mg/d d1-2, 4-5, 8-9, 11-12, 15, 22-23, 25-26, 29-30, 32-33).Treatment repeats every 42 days (d43 = cycle 2 d1). Standard intensification: For all patients, stem cells are mobilized by GMMG Standard protocols (CAD: cyclophosphamide, doxorubicin, dexamethasone) and G-CSF. At least 7.5x106 CD34+ cells/kg body weight are harvested. High dose treatment (melphalan 200mg/m², HDT) followed by autologous stem cell transplantation (ASCT) is started 4 - 6 weeks after CAD. For patients not in CR after HDT1, a second HDT is performed within 3 months.
IIA	Lenalidomide	maintenance treatment with Lenalidomide 10mg/d (increased to 15mg/d after 3 months) repeated every 28d. Maintenance treatment is planned for up to 36 months or until progression if progression occurs first.
IB	Isatuximab	Patients in arm IB are treated with 3 cycles RVd + Isatuximab (lenalidomide 25 mg/d p.o. d1 - 14 and d22 - 35; bortezomib 1.3 mg/m2 s.c. d1, 4, 8, 11, 22, 25, 29, 32;dexamethasone p.o. 20 mg/d d1-2, 4-5, 8-9, 11-12, 15, 22-23, 25-26, 29-30, 32-33).Isatuximab (10 mg/kg i.v. C1: d 1, 8, 15, 22, 29; C2-3: d 1, 15, 29).Treatment repeats every 42 days (d43 = cycle 2 d1). Standard intensification: For all patients, stem cells are mobilized by GMMG Standard protocols (CAD: cyclophosphamide, doxorubicin, dexamethasone) and G-CSF. At least 7.5x106 CD34+ cells/kg body weight are harvested. High dose treatment (melphalan 200mg/m², HDT) followed by autologous stem cell transplantation (ASCT) is started 4 - 6 weeks after CAD. For patients not in CR after HDT1, a second HDT is performed within 3 months.
IIB	Isatuximab	maintenance treatment with Lenalidomide 10mg/d (increased to 15mg/d after 3 months) + Isatuximab (10 mg/kg; C1: d1, 8, 15, 22; C2-C3: d1 + 15; C4-39:d1, repeated every 28d). Within the trial, maintenance treatment is planned for up to 36 months or until progression if progression occurs first.
IA	Dexamethasone	Patients in arm IA are treated with 3 cycles RVd (lenalidomide 25 mg/d p.o. d1 - 14 and d22 - 35; bortezomib 1.3 mg/m2 s.c. d1, 4, 8, 11, 22, 25, 29, 32; dexamethasone p.o. 20 mg/d d1-2, 4-5, 8-9, 11-12, 15, 22-23, 25-26, 29-30, 32-33).Treatment repeats every 42 days (d43 = cycle 2 d1). Standard intensification: For all patients, stem cells are mobilized by GMMG Standard protocols (CAD: cyclophosphamide, doxorubicin, dexamethasone) and G-CSF. At least 7.5x106 CD34+ cells/kg body weight are harvested. High dose treatment (melphalan 200mg/m², HDT) followed by autologous stem cell transplantation (ASCT) is started 4 - 6 weeks after CAD. For patients not in CR after HDT1, a second HDT is performed within 3 months.
IB	Lenalidomide	Patients in arm IB are treated with 3 cycles RVd + Isatuximab (lenalidomide 25 mg/d p.o. d1 - 14 and d22 - 35; bortezomib 1.3 mg/m2 s.c. d1, 4, 8, 11, 22, 25, 29, 32;dexamethasone p.o. 20 mg/d d1-2, 4-5, 8-9, 11-12, 15, 22-23, 25-26, 29-30, 32-33).Isatuximab (10 mg/kg i.v. C1: d 1, 8, 15, 22, 29; C2-3: d 1, 15, 29).Treatment repeats every 42 days (d43 = cycle 2 d1). Standard intensification: For all patients, stem cells are mobilized by GMMG Standard protocols (CAD: cyclophosphamide, doxorubicin, dexamethasone) and G-CSF. At least 7.5x106 CD34+ cells/kg body weight are harvested. High dose treatment (melphalan 200mg/m², HDT) followed by autologous stem cell transplantation (ASCT) is started 4 - 6 weeks after CAD. For patients not in CR after HDT1, a second HDT is performed within 3 months.
IB	Bortezomib	Patients in arm IB are treated with 3 cycles RVd + Isatuximab (lenalidomide 25 mg/d p.o. d1 - 14 and d22 - 35; bortezomib 1.3 mg/m2 s.c. d1, 4, 8, 11, 22, 25, 29, 32;dexamethasone p.o. 20 mg/d d1-2, 4-5, 8-9, 11-12, 15, 22-23, 25-26, 29-30, 32-33).Isatuximab (10 mg/kg i.v. C1: d 1, 8, 15, 22, 29; C2-3: d 1, 15, 29).Treatment repeats every 42 days (d43 = cycle 2 d1). Standard intensification: For all patients, stem cells are mobilized by GMMG Standard protocols (CAD: cyclophosphamide, doxorubicin, dexamethasone) and G-CSF. At least 7.5x106 CD34+ cells/kg body weight are harvested. High dose treatment (melphalan 200mg/m², HDT) followed by autologous stem cell transplantation (ASCT) is started 4 - 6 weeks after CAD. For patients not in CR after HDT1, a second HDT is performed within 3 months.
IIB	Lenalidomide	maintenance treatment with Lenalidomide 10mg/d (increased to 15mg/d after 3 months) + Isatuximab (10 mg/kg; C1: d1, 8, 15, 22; C2-C3: d1 + 15; C4-39:d1, repeated every 28d). Within the trial, maintenance treatment is planned for up to 36 months or until progression if progression occurs first.

Primary Outcome Measures

Name	Time	Method
MRD negativity after induction Treatment (comparison of arms IA and IB)	18 weeks after start of study treatment	Detection of minimal residual disease by flow cytometry (sensitivity at least 1e-5)
Progression Free Survival (PFS) after second randomization (arms IIA and IIB)	time from 2. randomization to progression or death from any cause whichever comes first, censored after three years of maintenance therapy	Response Evaluation by IMWG criteria

Secondary Outcome Measures

Name	Time	Method
Toxicity during induction and maintenance with respect to adverse events of CTC grade >3 (and specific adverse events of CTC grade > 2 as defined in the protocol and serious adverse events	: from first administration of study drug until 30 days after last administration of study drug or any drug of the study treatment or upon start of a new subsequent chemotherapy, whichever occurs first	toxicity according CTCAE Version v5.0
Quality of Life Assessment	assessed at baseline, after ca. 4.5 months, 9 months, (additionally after 12 months,if a second high dose therapy is administered) after 12 months of maintenance and at end of study (up to 50 months)	EORTC (European Organization of Research and Treatment of Cancer) -QLQC30 Questionnaire to assess the quality of life of cancer patients. Impairment of daily life is asked in 4 scales from "not at all" (best) to "very much" (worst scale), EORTC-QLQMY20 questionnaire to assess health-related quality of life in patients with multiple myeloma with 4 scales from "not at all (best scale) to "very much" (worst scale); EQ(EuroQol Group)-5D-5L Health questionnaire comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. Additionally a visual analogue scale from 100 (best) to 0 (worst scale) is used to assess the quality of health questionnaires.
Pharmakokinetic analyses of Isatuximab in induction treatment of patients in Arm IB (selected sites only)	Up to 18 weeks in induction treatment (C1: D1, before infusion, at end of infusion, 1 h after infusion, C1 D8,15,22,29 before infusion; C2 and 3:D1 before infusion	Determination of serum concentration of isatuximab at different timepoints before, during and after isatuximab infusion
MRD negativity after high dose therapy	After high dose therapy (9 or 12 months after start of therapy)	Detection of minimal residual disease by flow cytometry (sensitivity at least 1e-5)
Best response to treatment during the trial	response assessment after 3 months, 4,5 months, 5,5 months, 9 months (if applicable: 3 months later after 2. high dose therapy) subsequently every 3 months during maintenance treatment, up to 48 months after start of study treatment	Response evaluation by IMWG criteria
PFS 2 (PFS after next line of therapy) from 2. randomization	time from 2. randomization to time of overall end of trial (up to 75 months)	Response evaluation by IMWG criteria
Pharmakokinetic analyses of Isatuximab in maintenance treatment of patients in Arm IIB (selected sites only)	Up to 9 months (C1: D1, before infusion, at end of infusion, 1 h after infusion, C1 D8,15,22 before infusion, C2 -9, D1: before infusion	Determination of serum concentration of isatuximab at different timepoints
to compare the four treatment arms (IA-IIA, IA-IIB, IB-IIA, IB-IIB) regarding Progression free survival (PFS)	time from 1. randomization (study inclusion) to progression or death whichever comes first (assessed up to 79 months)	Response evaluation by IMWG criteria
to compare all 4 treatment arms (IA-IIA, IA-IIB, IB-IIA, IB-IIB) regarding overall survival (OS) from time of 1.randomization	time from randomisation to time of death from any cause (assessed up to 79 months)	survival status
Overall survival from second randomization	time from 2. randomization to time of death from any cause (assessed up to 75 months)	survival status
Complete Response (CR) rates after induction therapy	After induction treatment (18 weeks after start of treatment)	Response Evaluation by IMWG criteria
Complete Response (CR) after high dose therapy	After high dose therapy (9 or 12 months after start of therapy)	Response Evaluation by IMWG criteria
Complete Response (CR) during/after maintenance therapy	During/after maintenance therapy (6 months after start of therapy up to 36 months of maintenance therapy)	Response Evaluation by IMWG criteria
MRD negativity during and after maintenance therapy	up to 36 months after start of maintenance therapy	Detection of minimal residual disease by flow cytometry (sensitivity at least 1e-5)

Trial Locations

Locations (73)

Helios Klinikum Bad Saarow, Klinik für Hämatologie, Onkologie und Palliativmedizin; 🇩🇪 Bad Saarow, Germany

Uniklinik RWTH Aachen, Klinik für Hämatologie, Onkologie, Hämostaseologie und Stammzelltransplantation; 🇩🇪 Aachen, Germany

Klinikum Darmstadt, Med. Klinik V, Hämatologie/Onkologie; 🇩🇪 Darmstadt, Germany

Klinikum Bielefeld, Klinik für Hämatologie, Onkologie und Palliativmedizin; 🇩🇪 Bielefeld, Germany

Medizinische Universitätsklinik, Knappschaftskrankenhaus; 🇩🇪 Bochum, Germany

Universitätsklinikum Düsseldorf, Klinik für Hämatologie,Onkologie und Klin. Immunologie; 🇩🇪 Düsseldorf, Germany

Universitätsklinikum Essen, Klinik für Hämatologie; 🇩🇪 Essen, Germany

Carl-Thiem-Klinikum Cottbus gGmbH, II. Medizinische Klinik; 🇩🇪 Cottbus, Germany

Vivantes Klinikum Neukölln, Klinik für Hämatologie und Onkologie; 🇩🇪 Berlin, Germany

Charité, Campus Benjamin Franklin , III. Medizinische Abteilung (Hämatologie/Onkologie); 🇩🇪 Berlin, Germany

HELIOS Klinikum, Klinik für Hämatologie, Onkologie und Immunologie; 🇩🇪 Berlin, Germany

KRH Klinikum Siloah, Klinik für Hämatologie und Onkologie; 🇩🇪 Hannover, Germany

Kath. Krankenhaus Hagen gGmbH, Abt. Hämatologie/Onkologie; 🇩🇪 Hagen, Germany

Med. Klinik A, Klinikum der Stadt Ludwigshafen am Rhein gGmbH; 🇩🇪 Ludwigshafen am Rhein, Germany

Studienzentrum Aschaffenburg; 🇩🇪 Aschaffenburg, Germany

Johanniter Krankenhaus Bonn; 🇩🇪 Bonn, Germany

Klinikum Chemnitz GmbH, Innere Medizin III; 🇩🇪 Chemnitz, Germany

Onkologisches Studienzentrum Darmstadt; 🇩🇪 Darmstadt, Germany

Marien Hospital Düsseldorf GmbH, Klinik für Onkologie, Hämatologie und Palliativmedizin; 🇩🇪 Düsseldorf, Germany

Universitätsklinik Erlangen; 🇩🇪 Erlangen, Germany

Gemeinschaftspraxis Prof. Dr. Michael Kiehl und Dipl. Med. Wolfgang Stein; 🇩🇪 Frankfurt (Oder), Germany

Universitätsklinikum des Saarlandes, Innere Medizin I; 🇩🇪 Homburg (Saar), Germany

Klinikum Fulda, Klinisches Studienzentrum GmbH; 🇩🇪 Fulda, Germany

Klinikum Osnabrück GmbH; 🇩🇪 Osnabrück, Germany

Universitätsklinikum Hamburg Eppendorf, Zentrum für Onkologie, Studienzentrale der II. Medizinischen Klinik; 🇩🇪 Hamburg, Germany

Centrum für Hämatologie und Onkologie Bethanien; 🇩🇪 Frankfurt am Main, Germany

Agaplesion Markus Krankenhaus, Med. Klinik I; 🇩🇪 Frankfurt am Main, Germany

Krankenhaus St. Vincentius der evangelischen Stadtmission Heidelberg, Abt. Hämatologie, Onkologie, Rheumatologie; 🇩🇪 Heidelberg, Germany

Studiengesellschaft Onkologie Bielefeld GbR; 🇩🇪 Bielefeld, Germany

Universitätsklinikum Bonn, Medizinische Klinik und Poliklinik III, Schwerpunkt Onkologie, Hämatologie und Rheumatologie; 🇩🇪 Bonn, Germany

Städtisches Klinikum Braunschweig, Med. Klinik III, Hämatologie und Onkologie; 🇩🇪 Braunschweig, Germany

HELIOS St. Johannes Klinik, Akademisches Krankenhaus der Heinrich-Heine-Universität Düsseldorf; 🇩🇪 Duisburg, Germany

Universitätsklinikum Frankfurt, Goethe-Universität Medizinische Klinik II; 🇩🇪 Frankfurt am Main, Germany

Asklepios Klinik Hamburg St. Georg; 🇩🇪 Hamburg, Germany

Katholisches Karl-Leisner-Klinikum gGmbH, Wilhelm-Anton-Hospital Goch, Klinik für Hämatologie - Onkologie; 🇩🇪 Goch, Germany

Universitätsklinik der Justus-Liebig-Universität, Medizinische Klinik IV; 🇩🇪 Gießen, Germany

Immunologisch-onkologisches MVZ am Siloah Krankenhaus; 🇩🇪 Hannover, Germany

Marien Hospital Herne; 🇩🇪 Herne, Germany

SLK Kliniken Heilbronn, Med. Klinik III; 🇩🇪 Heilbronn, Germany

Westpfalz-Klinikum GmbH, Klinik für Innere Medizin I; 🇩🇪 Kaiserslautern, Germany

Uniklinik Köln, Klinik I für Innere Medizin; 🇩🇪 Köln, Germany

Gemeinschaftspraxis für Hämatologie und Onkologie am Caritas Krankenhaus; 🇩🇪 Lebach, Germany

Städtisches Klinikum Karlsruhe; 🇩🇪 Karlsruhe, Germany

Universitätsmedizin der Johannes Gutenberg-Universität Mainz, III. Med. Klinik; 🇩🇪 Mainz, Germany

III. Medizinische Klinik Hämatologie und Internistische Onkologie; 🇩🇪 Mannheim, Germany

Philipps-Universität Marburg, Hämatologie/Onkologie/Immunologie; 🇩🇪 Marburg, Germany

Mannheimer Onkologie Praxis; 🇩🇪 Mannheim, Germany

Mühlenkreiskliniken (AöR) Johannes Wesling Klinikum Minden, Hämatologie/Onkologie, Hämostaseologie und Palliativmedizin; 🇩🇪 Minden, Germany

Krankenhaus Maria Hilf GmbH, Franziskuskrankenhaus, Med. Klinik I; 🇩🇪 Mönchengladbach, Germany

Krankenhaus Barmherzige Brüder, Klinik für Onkologie und Hämatologie; 🇩🇪 Regensburg, Germany

Brüderkrankenhaus St. Josef Paderborn, Klinik für Hämatologie und Onkologie; 🇩🇪 Paderborn, Germany

Klinikum Mutterhaus der Borromäerinnen gGmbH; 🇩🇪 Trier, Germany

ZAHO-Zentrum für ambulante Hämatologie und Onkologie, Standort Siegburg; 🇩🇪 Siegburg, Germany

Klinikum Stuttgart, Stuttgart Cancer Center, Tumorzentrum Eva Mayr-Stihl; 🇩🇪 Stuttgart, Germany

Onkologische Schwerpunktpraxis Speyer; 🇩🇪 Speyer, Germany

University Hospital Tübingen, Med. Klinik und Poliklinik, Abt. II; 🇩🇪 Tübingen, Germany

Schwarzwald-Baar Klinikum, Innere Medizin II; 🇩🇪 Villingen-Schwenningen, Germany

Ev. Krankenhaus Essen-Werden gGmbH, Zentrum für Innere Medizin, Klinik für Hämatologie, Onkologie und Stammzelltransplantation; 🇩🇪 Essen, Germany

Zentrum für ambulante Hämatologie und Onkologie (ZAHO); 🇩🇪 Bonn, Germany

Diakonie-Klinikum Schwäbisch Hall gGmbH, Innere Medizin III; 🇩🇪 Schwäbisch Hall, Germany

Rems-Murr-Kliniken gGmbH; 🇩🇪 Winnenden, Germany

Asklepios Klinik Hamburg Altona, II. Med. Klinik; 🇩🇪 Hamburg, Germany

Universitätsklinikum Carl Gustav Carus Dresden, an der Technischen Universität Dresden, Medizinische Klinik und Poliklinik I; 🇩🇪 Dresden, Germany

St. Antonius-Hospital Eschweiler, Klinik für Hämatologie / Onkologie; 🇩🇪 Eschweiler, Germany

Klinikum Frankfurt (Oder) GmbH; 🇩🇪 Frankfurt (Oder), Germany

Onkologische Schwerpunktpraxis Heidelberg; 🇩🇪 Heidelberg, Germany

Universitätsklinikum Leipzig AöR, Medizinische Klinik und Poliklinik I-Hämatologie und Zelltherapie, Internistische Onkologie, Hämostaseologie; 🇩🇪 Leipzig, Germany

Krankenhaus Nordwest, Institut für Klinisch-Onkologische Forschung; 🇩🇪 Frankfurt am Main, Germany

Gemeinschaftspraxis für Hämatologie und Onkologie, Onkologisches Zentrum; 🇩🇪 Saarlouis, Germany

University Hospital Heidelberg, Med. Klinik V; 🇩🇪 Heidelberg, Germany

Universitätsklinikum Münster, Med. Klinik A; 🇩🇪 Münster, Germany

Bundeswehrkrankenhaus Ulm, Abteilung Innere Medizin - Hämatologie und internistische Onkologie; 🇩🇪 Ulm, Germany

Praxisklinik für Hämatologie und Onkologie; 🇩🇪 Koblenz, Germany