A Study of Modakafusp Alfa in Adult Participants With Multiple Myeloma

Sponsor

Takeda (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05556616

Collaborator

(none)

144

Enrollment

Locations

Arms

62.9

Anticipated Duration (Months)

2.7

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The main aims of this study is to test for any side effects from modakafusp alfa in combination therapy and to determine the recommended dose of combination therapy with modakafusp. The dose of modakafusp alfa will be increased a little at a time until the highest dose that does not cause harmful side effects is found. Participants will be given modakafusp alfa through a vein.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Modakafusp alfa Drug: Lenalidomide Drug: Bortezomib Drug: Carfilzomib Drug: Daratumumab Drug: Pomalidomide	Phase 1

Detailed Description

The drug being tested in this study is called modakafusp alfa (TAK-573). The study will evaluate the safety, tolerability and determine the recommended dose of modakafusp alfa in combination with lenalidomide in participants with newly diagnosed multiple myeloma (NDMM), or in combination with pomalidomide, bortezomib, carfilzomib, or daratumumab in participants with relapsed/refractory multiple myeloma (RRMM).

The study consists of 3 Groups: Group 1: NDMM Maintenance Therapy, Group 2: RRMM Doublets, Group 3: RRMM Triplets.

The study will enroll approximately 18 participants in Group 1, 54 in Group 2, and 72 in Group 3. Participants will be assigned to one of the following treatment groups as given below:

Group 1 (NDMM Maintenance) Arm 1: Modakafusp alfa + Lenalidomide
Group 2 (RRMM Doublets) Arm 2: Modakafusp alfa + Pomalidomide
Group 2 (RRMM Doublets) Arm 3: Modakafusp alfa + Bortezomib
Group 2 (RRMM Doublets) Arm 4: Modakafusp alfa + Carfilzomib
Group 3 RRMM Triplets) Arm A: Modakafusp alfa + Pomalidomide + Bortezomib
Group 3 (RRMM Triplets) Arm B: Modakafusp alfa + Carfilzomib + Pomalidomide
Group 3 (RRMM Triplets) Arm C: Modakafusp alfa + Daratumumab + Carfilzomib
Group 3 (RRMM Triplets) Arm D: Modakafusp alfa + Daratumumab + Pomalidomide

The study will be conducted worldwide. The maximum treatment duration in this study for Group 1 is until disease progression or unacceptable toxicity, or up to 2 years for minimal/measurable residual disease (MRD) negative participants, whichever occurs first. The maximum treatment duration in this study for Group 2 and Group 3 is until disease progression or unacceptable toxicity, whichever occurs first. Overall time to participate in the study is approximately up to 5 years.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

144 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1b Open-label Study to Evaluate the Safety and Tolerability of Intravenous Modakafusp Alfa as Part of Combination Therapy in Adult Patients With Multiple Myeloma

Actual Study Start Date :

Oct 27, 2022

Anticipated Primary Completion Date :

Jul 24, 2025

Anticipated Study Completion Date :

Jan 25, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1 (NDMM Maintenance) Arm 1: Modakafusp alfa + Lenalidomide Modakafusp alfa, infusion intravenously (IV), once on Day 1, once every 4 weeks (Q4W), in combination with Lenalidomide capsules orally once daily continuously on Days 1 to 28, in a 28-day (4-week) treatment cycle until disease progression, unacceptable toxicity, any other discontinuation criterion is met, or to a maximum of 2 years for MRD-negative participants, whichever occurs first.	Drug: Modakafusp alfa Modakafusp alfa intravenous infusion. Other Names: TAK-573 Drug: Lenalidomide Lenalidomide capsules orally.
Experimental: Group 2 (RRMM Doublets) Arm 2: Modakafusp alfa + Pomalidomide Modakafusp alfa, infusion IV, once on Day 1, Q4W in combination with Pomalidomide capsules orally once daily on Days 1 to 21 in a 28-day (4-week) treatment cycle until disease progression, unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first.	Drug: Modakafusp alfa Modakafusp alfa intravenous infusion. Other Names: TAK-573 Drug: Pomalidomide Pomalidomide capsules orally.
Experimental: Group 2 (RRMM Doublets) Arm 3: Modakafusp alfa + Bortezomib Modakafusp alfa, infusion IV, once on Day 1, Q4W in combination with Bortezomib injection subcutaneously on Days 1, 8 and 15 for the first 8 cycles and subsequently on Days 1 and 8 of a 28-day (4-week) treatment cycle until disease progression, unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first.	Drug: Modakafusp alfa Modakafusp alfa intravenous infusion. Other Names: TAK-573 Drug: Bortezomib Bortezomib injection subcutaneously.
Experimental: Group 2 (RRMM Doublets) Arm 4: Modakafusp alfa + Carfilzomib Modakafusp alfa, infusion IV, once on Day 1, Q4W in combination with Carfilzomib IV, on Day 1, 8 and 15 of a 28-day (4-week) treatment cycle until disease progression, unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first.	Drug: Modakafusp alfa Modakafusp alfa intravenous infusion. Other Names: TAK-573 Drug: Carfilzomib Carfilzomib intravenous infusion.
Experimental: Group 3 (RRMM Triplets) Arm A: Modakafusp alfa + Pomalidomide + Bortezomib Modakafusp alfa, infusion IV, once on Day 1, Q4W in combination with Pomalidomide capsules orally once daily on Days 1 to 21 in a 28-day (4-week) treatment cycle along with Bortezomib injection subcutaneously on Days 1, 8 and 15 for the first 8 cycles and subsequently on Days 1 and 8 of a 28-day (4-week) treatment cycle until disease progression, unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first.	Drug: Modakafusp alfa Modakafusp alfa intravenous infusion. Other Names: TAK-573 Drug: Bortezomib Bortezomib injection subcutaneously. Drug: Pomalidomide Pomalidomide capsules orally.
Experimental: Group 3 (RRMM Triplets) Arm B: Modakafusp alfa + Carfilzomib + Pomalidomide Modakafusp alfa, infusion IV, once on Day 1, Q4W in combination with Carfilzomib IV, on Days 1, 8 and 15 of a 28-day (4-week) treatment cycle along with Pomalidomide capsules orally once daily on Days 1 to 21 in a 28-day (4-week) treatment cycle until disease progression, unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first.	Drug: Modakafusp alfa Modakafusp alfa intravenous infusion. Other Names: TAK-573 Drug: Carfilzomib Carfilzomib intravenous infusion. Drug: Pomalidomide Pomalidomide capsules orally.
Experimental: Group 3 (RRMM Triplets) Arm C: Modakafusp alfa + Daratumumab + Carfilzomib Modakafusp alfa, infusion IV, once on Day 1, Q4W in combination with Daratumumab injection subcutaneously on Days 1, 8, 15 and 22 of Cycles 1 and 2, further followed by on Days 1 and 15 of Cycles 3 to 6, thereafter on Day 1 on a 28-day (4-week) treatment cycle along with Carfilzomib IV on Day 1, 8 and 15 of treatment cycle along with Pomalidomide capsules orally once daily on Days 1 to 21 in a 28-day (4-week) treatment cycle until disease progression, unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first.	Drug: Modakafusp alfa Modakafusp alfa intravenous infusion. Other Names: TAK-573 Drug: Carfilzomib Carfilzomib intravenous infusion. Drug: Daratumumab Daratumumab injection subcutaneously.
Experimental: Group 3 (RRMM Triplets) Arm D: Modakafusp alfa + Daratumumab + Pomalidomide Modakafusp alfa, infusion IV, once on Day 1, Q4W in combination with Daratumumab injection subcutaneously on Days 1, 8, 15 and 22 of Cycles 1 and 2, further followed by on Days 1 and 15 of Cycles 3 to 6, thereafter on Day 1 on a 28-day (4-week) treatment cycle along with Pomalidomide capsules orally once daily on Days 1 to 21 in a 28-day (4-week) treatment cycle until disease progression, unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first.	Drug: Modakafusp alfa Modakafusp alfa intravenous infusion. Other Names: TAK-573 Drug: Daratumumab Daratumumab injection subcutaneously. Drug: Pomalidomide Pomalidomide capsules orally.

Outcome Measures

Primary Outcome Measures

Number of Participants With Dose-limiting Toxicities (DLTs) [Cycle 1 (Cycle length is 28 days)]
DLT will be defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0: Grade 5 AE; Hematologic toxicity: Nonfebrile Grade 4 neutropenia lasting more than 7 consecutive days/Grade greater than or equal to (>=) 3 febrile neutropenia; Grade 4 thrombocytopenia lasting more than 14 consecutive days, Grade 3 thrombocytopenia with clinically significant bleeding; any other Grade 4 with exceptions; Nonhematologic Grade 3 or higher toxicities unrelated to the underlying disease with exceptions; Delay in Cycle 2 by more than 14 days due to a lack of adequate recovery of treatment-related hematological or nonhematologic toxicities.
Number of Participants Reporting one or More Treatment Emergent Adverse Events (TEAEs) [Up to approximately 5 years]

Secondary Outcome Measures

Progression Free Survival (PFS) [Up to approximately 5 years]
PFS is defined as the time from the date of the first dose administration to the date of first documentation of confirmed progression of disease (PD) or death due to any cause, whichever occurs first. PD will be determined by International Myeloma Working Group (IMWG) criteria. PD: increase of >=25 percent (%) from lowest response value in any one or more of the following: serum M-component increase >=0.5 gram per deciliter (g/dL) or urine M-component increase >=200 milligram (mg)/24-hour; difference between involved and uninvolved free light chains (FLC) levels increase must be greater than (>) 10 milligram per deciliter (mg/dL); bone marrow plasma cell >=10%; definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; development of hypercalcemia that can be attributed solely to plasma cell proliferative disorder.
Overall Response Rate (ORR) [Up to approximately 5 years]
ORR is defined as the percentage of participants who achieved a partial response rate (PR) or better during the study as defined by IMWG Uniform Response Criteria. PR: >=50% reduction of serum M-protein and >=90% reduction in urine M-protein or less than (<) 200 mg/24 hour, or >=50% decrease in uninvolved FLC or >=50% reduction in plasma cells. At baseline, a >=50% decrease in size of soft tissue plasmacytomas is required.
Duration of Response (DOR) [Up to approximately 5 years]
DOR is defined as the time from the date of first documentation of response PR or better to the date of first documentation of PD or death due to any cause. PR: >=50% reduction of serum M-protein and >=90% reduction in urine M-protein or <200 mg/24 hour, or >=50% decrease in uninvolved FLC or >=50% reduction in plasma cells. At baseline, a >=50% decrease in size of soft tissue plasmacytomas is required. PD: increase of >=25% from lowest response value in any one or more of the following: serum M-component increase >=0.5 g/dL or urine M-component increase >=200 mg/24-hour; difference between involved and uninvolved FLC levels increase must be >10 mg/dL; bone marrow plasma cell >=10%; definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; development of hypercalcemia that can be attributed solely to plasma cell proliferative disorder.
Groups 2 and 3: Overall Survival (OS) [Up to approximately 5 years]
OS is defined as the time from the first dose of administration to the date of death, due to any cause. Participants without documentation of death at the time of analysis will be censored at the date last known to be alive.
Groups 2 and 3: Time to Progression (TTP) [Up to approximately 5 years]
TTP is defined as the time from the date of the first dose until the earliest date of confirmed PD per IMWG, or death due to PD. PD: increase of >=25% from lowest response value in any one or more of the following: serum M-component increase >=0.5 g/dL or urine M-component increase >=200 mg/24-hour; difference between involved and uninvolved FLC levels increase must be >10 mg/dL; bone marrow plasma cell >=10%; definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; development of hypercalcemia that can be attributed solely to plasma cell proliferative disorder.
Groups 2 and 3: Time to Next Treatment (TTNT) [Up to approximately 5 years]
TTNT is defined as the time from the date of first dose administration to the date of the first dose initiation of the next line of antineoplastic therapy, for any reason.
Groups 2 and 3: Disease Control Rate (DCR) [Up to approximately 5 years]
DCR is defined as the percentage of participants who achieved a stable disease (SD) or better during the study as defined by IMWG Uniform Response Criteria. SD is defined as no known evidence of progressive disease or new bone lesions.
Groups 2 and 3: Clinical Benefit Rate (CBR) [Up to approximately 5 years]
CBR: as percentage of participants with measurable disease who had response of sCR, CR, VGPR, PR, or minimal response per IMWG criteria.CR: as negative immunofixation of serum and urine, disappearance of any soft tissue plasmacytomas, <5% plasma cells in bone marrow; in participants for whom only measurable disease is by serum FLC level, normal FLC ratio of 0.26 to 1.65 in addition to CR criteria is required.sCR:CR+normal FLC ratio,absence of clonal plasma cells (immunohistochemistry) or 2-to 4-color flow cytometry.VGPR:serum,urine M-protein detectable by immunofixation,not by electrophoresis or >=90%reduction,<100mg/24hrs(in those with only measurable disease by serum FLC levels,requires >90%decrease in involved-uninvolved FLC level difference).PR: >=50% reduction of serum M-protein; >=90% reduction in urine M-protein or <200 mg/24 hour, or >=50% decrease in uninvolved FLC or >=50% reduction in plasma cells.At baseline,>=50% decrease in size of soft tissue plasmacytomas is required.
Groups 2 and 3: Time to Response (TTR) [Up to approximately 5 years]
TTR is defined as the time from the date of the first dose administration to the date of the first documentation of objective response as defined by IMWG criteria.
Group 1: Percentage of Participants with MRD Negativity Status at a Sensitivity of 10^-5 [Up to approximately 2 years after treatment]
MRD negativity at a sensitivity of 10^-5 is defined as the percentage of participants who have achieved MRD negative status in all participants.
Group 3: Percentage of Participants with MRD Negativity Status at a Sensitivity of 10^-5 in Participants Achieving CR [Up to approximately 5 years]
MRD negativity at a sensitivity of 10^-5 is defined as the percentage of participants who have achieved MRD negative status in participants achieving suspected CR. CR is defined as negative immunofixation of serum and urine, disappearance of any soft tissue plasmacytomas, and <5% plasma cells in bone marrow; in participants for whom only measurable disease is by serum FLC level, normal FLC ratio of 0.26 to 1.65 in addition to CR criteria is required.
Group 1: Duration of MRD Negativity Status at a Sensitivity of 10^-5 in Participants Achieving MRD Negativity [Up to approximately 2 years after treatment]
Duration of MRD negativity (10^-5) is defined as the duration from the start of MRD negative status to the time of reappearance of detectable MRD, PD, or death. PD: increase of >=25% from lowest response value in any one or more of the following: serum M-component increase >=0.5 g/dL or urine M-component increase >=200 mg/24-hour; difference between involved and uninvolved FLC levels increase must be >10 mg/dL; bone marrow plasma cell >=10%; definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; development of hypercalcemia that can be attributed solely to plasma cell proliferative disorder.
Group 3: Duration of MRD Negativity Status at a Sensitivity of 10^-5 in Participants Achieving MRD Negativity [Up to approximately 5 years]
Duration of MRD negativity (10^-5) is defined as the duration from the start of MRD negative status to the time of reappearance of detectable MRD, PD, or death. PD: increase of >=25% from lowest response value in any one or more of the following: serum M-component increase >=0.5 g/dL or urine M-component increase >=200 mg/24-hour; difference between involved and uninvolved FLC levels increase must be >10 mg/dL; bone marrow plasma cell >=10%; definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; development of hypercalcemia that can be attributed solely to plasma cell proliferative disorder.
Number of Participants With Positive Anti-drug Antibodies (ADA) and Neutralizing Antibody (NAb) [Up to approximately 5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Group 1 (NDMM maintenance: modakafusp alfa/lenalidomide) only must have:
NDMM based on standard IMWG diagnostic criteria, have undergone standard of care (SOC) induction therapy including an ASCT, and have achieved a major clinical response.
A history of measurable disease documented at time of diagnosis (before induction and ASCT).
Undergone ASCT within the 12 months of the start of induction therapy and completed ASCT within 180 days before enrollment. Time to initiation of maintenance therapy: participants may start maintenance therapy as early as 60 days after transplant and up to 180 days after transplant. Consolidation cycles are allowed.
Post ASCT MRD positive (10^-5 threshold by local SOC methods or central assessment, if a prior local MRD assessment had not been performed).
No prior progression after initial therapy (at any time before starting maintenance). Participants whose induction therapy was changed due to suboptimal response or toxicity will be eligible if they do not meet criteria for progression. In addition, no more than 2 regimens will be allowed before ASCT, excluding dexamethasone alone.
No prior allogeneic hematopoietic stem cell transplant or solid organ transplant.
Recovered to Grade less than or equal to (<=) 1 autologous stem cell transplant (ASCT) -related toxicities from the reversible effects of ASCT (except for alopecia and amenorrhea).
Groups 2 and 3 (RRMM doublets and RRMM triplets) must have:
Measurable disease, defined as at least one of the following:

Serum M-protein >=0.5 g/dL (>=5 g/L) on serum protein electrophoresis (SPEP).
Urine M-protein >=200 mg/24 hours on urine protein electrophoresis (UPEP).
Serum free light chain (FLC) assay result with an involved FLC level >=10 mg/dL (>=100 mg/L), provided the serum FLC ratio is abnormal (per IMWG criteria).

A confirmed diagnosis of MM according to IMWG criteria with documented disease progression in need of additional therapy as determined by the investigator.
For Group 2 RRMM doublet arms only: Participants who have received at least 3 prior lines of antimyeloma therapy, including at least 1 proteasome inhibitor (PI), 1 immunomodulatory (IMiD) and 1 anti-CD38 monoclonal antibody (mAb) drug, or who are triple refractory to a PI, an IMiD, and an anti-CD38 mAb drug regardless of the number of prior line(s) of therapy.

For Group 3 RRMM triplet arms only: Participants who have received 1 to 3 prior lines of antimyeloma therapy including at least 1 PI and, 1 IMiD, and who are not refractory to the combination partners.

For anti-CD38 arms, forced expiratory volume in 1 second >=50% by pulmonary function testing.
For carfilzomib arms, baseline echocardiogram with left ventricular ejection fraction >=50%.

Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 at screening
Has adequate organ function at screening as determined by the laboratory values required for enrollment: Absolute neutrophil count (ANC) >=1000 per cubic millimeter (/mm^{3) (or >=1*10}9/L); Platelets >=75,000/mm^{3 (>=75*10}9/L); Hemoglobin >=8.0 g/dL; estimated creatinine clearance >=30 mL/min (Cockcroft-Gault formula); Total serum bilirubin <=2.0Upper limit of normal (ULN); an exception for participants with Gilbert's syndrome may be granted after discussion with the sponsor; Liver transaminases (alanine aminotransferase [ALT])/aspartate aminotransferase [AST]) <=3.0ULN.
Has recovered from adverse reactions to prior myeloma treatment or procedures (example, chemotherapy, immunotherapy, radiation therapy) to NCI CTCAE Version 5.0 Grade <=1 or baseline treatment or have the toxicity established as sequela, except for sensory or motor neuropathy, which should have recovered to Grade <=2 or baseline; Grade 1 for bortezomib arm.

Exclusion criteria:

Currently participating in another MM interventional study, including other clinical trials with investigational agents (including investigational vaccines or investigational medical device for disease under study) throughout the duration of this study.
Received previous treatment with modakafusp alfa.
Has a diagnosis of primary amyloidosis, Waldenström disease, monoclonal gammopathy of undetermined significance or smoldering MM per IMWG criteria or standard diagnostic criteria, plasma cell leukemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), lymphoplasmacytic lymphoma.
Has had another malignancy within the previous 3 years, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, cervical carcinoma in situ, resected colorectal adenomatous polyps, breast cancer in situ, or other malignancy for which the participant is not on active anticancer therapy and that in the opinion of the local investigator, with concurrence with the principal investigator, is considered cured with minimal risk of recurrence within 3 years.
Has evidence of CNS involvement and/or meningeal involvement due to MM exhibited during screening.
Has a known severe allergic or anaphylactic reactions to human recombinant proteins or excipients used in the modakafusp alfa formulation or to the study combination agents, the study medications, their analogs, or excipients in the various formulations of any agent per the prescribing information.
Is seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Participants with resolved infection (that is, participants who are HBsAg negative but positive for antibodies to hepatitis B core antigen and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION: Participants with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) and, a known history of prior HBV vaccination do not need to be tested for HBV DNA by PCR.
Has a known history of seropositivity for HIV.
Is seropositive for hepatitis C (anti-hepatitis C virus antibody positive or anti-hepatitis C virus-RNA quantitation positive). Exception: Participants with a sustained virologic response with undetectable HCV RNA level at least 12 weeks after completion of antiviral therapy.
For bortezomib arms: participants received a strong cytochromes P450 (CYP3A4) inducer within 5 half-lives prior to randomization.
The participant has a chronic condition requiring the use of systemic corticosteroids

10 mg/dL of prednisone or equivalent, in addition to any required corticosteroids for the treatment of MM.

Has QT interval corrected with Fridericia correction method (QTcF) >480 millisecond (ms) (Grade >=2).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arkansas for Medical Sciences (UAMS) - Winthrop P. Rockefeller Cancer Institute (Arkansas Cancer Research Center)	Little Rock	Arkansas	United States	72205
2	University of California Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
3	Scripps Health	San Diego	California	United States	92121
4	University Of Colorado At Denver and Health Science Center	Aurora	Colorado	United States	80045
5	Miami Cancer Institute at Baptist Health, Inc.	Miami	Florida	United States	33176
6	The University of Iowa Hospitals & Clinics	Iowa City	Iowa	United States	52242
7	Cancer Center of Kansas	Wichita	Kansas	United States	67214
8	Cancer Center At Greater Baltimore Medical Center	Baltimore	Maryland	United States	21153
9	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
10	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
11	Mayo Clinic	Rochester	Minnesota	United States	55905
12	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada	United States	89119
13	New York University School of Medicine	New York	New York	United States	10016
14	Weill Cornell Medicine/New York Presbyterian Hospital	New York	New York	United States	10021
15	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029
16	Memorial Sloan Kettering Cancer Center - Main Campus	New York	New York	United States	10065
17	Novant Health Cancer Institute	Charlotte	North Carolina	United States	28204
18	Gabrail Cancer Center Research	Canton	Ohio	United States	44718
19	Vanderbilt University Medical Center (VUMC)	Nashville	Tennessee	United States	37232
20	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
21	Intermountain Healthcare - Lds Hospital	Salt Lake City	Utah	United States	84103
22	Universitaetsklinikum St. Poelten	St. Poelten	Saint Poelten	Austria	3100
23	Ordensklinikum Linz GmbH Elisabethinen	Linz		Austria	5020
24	Uniklinikum Salzburg, Landeskrankenhaus, Universitatsklinik fur Innere Medizin III der PMU	Salzburg		Austria	5020
25	CHU UCL Namur site Godinne	Yvoir	Namur	Belgium	5530
26	AZ Delta	Roeselare	Roeselare West-Vlaanderen	Belgium	8800
27	University Hospitals Leuven	Leuven		Belgium	3000
28	Centre Hospitalier Universitaire Sart Tilman	Liege		Belgium	4000
29	University Health Network (UHN) - Princess Margaret Cancer Centre - Myeloma Clinic	Toronto	Ontario	Canada	M5G 2M9
30	McGill University Health Centre (MUHC) - The Montreal General Hospital (MGH) - Cedars Cancer Centre	Montreal	Quebec	Canada	H4A 3JL
31	Soroka University Medical Center (Sumc)	Be'er Sheva	Beer Sheva Negev	Israel	84101
32	Assuta Ashdod Medical Center	Ashdod		Israel	7747629
33	Rambam Health Care Campus (RHCC) - Meyer Children's Hospital - Pediatric Diabetes & Obesity Clinic	Haifa		Israel	31999
34	Rabin Medical Center, Beilinson Campus	Petah Tikva		Israel	49100
35	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS	Meldola		Italy	47014
36	IRCCS-Istituto Europeo di Oncologia, Division di Oncoematologia	Milan		Italy	20141
37	Azienda Ospedaliera Niguarda Ca' Granda	Milan		Italy	20162
38	Universita degli Studi di Napoli Federico II	Napoli		Italy	80131
39	Azienda Unita Sanitaria Locale di Ravenna - Ospedale S. Maria delle Croci di Ravenna	Ravenna		Italy	48121
40	Regina Elena National Cancer Institute	Rome		Italy	144
41	Universita Cattolica del Sacro Cuore - Policlinico Universitario Agostino Gemelli, UOC Ematologia	Rome		Italy	168
42	Catalan Institute of Oncology (ICO) Hospitalet	Barcelona	Catalunya	Spain	8907
43	Hospital Universitario de Canarias	Santa Cruz De Tenerife	Tenerife	Spain	38320
44	Hospital Universitario La Fe de Valencia	Valencia	Valecia	Spain	46026
45	Hospital De Cabuenes	Gijon		Spain	33394
46	Hospital Universitario Virgen de la Victoria	Malaga		Spain	29010
47	Clinica Universidad de Navarra, Dept of Oncology	Pamplona		Spain	31008
48	Ente Ospedaliero Cantonale (EOC) Istituto Oncologico della Svizzera Italiana (IOSI)	Bellinzona		Switzerland	6500
49	Inselspital Bern	Bern		Switzerland	3010
50	Geneva University Hospital	Geneve		Switzerland	1211
51	Ambrose King Centre-Royal London Hospital-Barts Health NHS Trust	London	Greater London	United Kingdom	E1 1BB
52	Guy's Hospital - Guy's & St Thomas' NHS Foundation Trust	London		United Kingdom	SE1 9RT
53	Hammersmith Hospital - Imperial College Healthcare NHS Trust	London		United Kingdom	W12 0HS
54	Northern Centre for Cancer Care,The Newcastle Upon Tyne Hospitals NHS Foundation Trust	Newcastle upon Tyne		United Kingdom	NE7 7DN