A Study of Obinutuzumab, Rituximab, Polatuzumab Vedotin, and Venetoclax in Relapsed or Refractory Follicular Lymphoma (FL) or Diffuse Large B-Cell Lymphoma (DLBCL)

Phase 1

Completed

• Conditions: Non-Hodgkin's Lymphoma
• Interventions: Drug: Obinutuzumab; Drug: Rituximab; Drug: Polatuzumab Vedotin; Drug: Venetoclax

• Registration Number: NCT02611323
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

This study will evaluate the safety, efficacy, and pharmacokinetics of induction treatment with obinutuzumab, polatuzumab vedotin, and venetoclax in participants with relapsed or refractory FL, and with rituximab, polatuzumab vedotin, and venetoclax in participants with DLBCL. Participants with FL who achieve complete response (CR), partial response (PR), or stable disease (SD) at the end of induction therapy will receive post-induction treatment with obinutuzumab and venetoclax, and participants with DLBCL who achieve CR or PR at the end of induction (EOI) will receive post-induction treatment with rituximab and venetoclax.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-11-19
• Study First Submitted QC: 2015-11-19
• Study First Posted: 2015-11-20
• Study Start: 2016-03-09
• Primary Completion: 2022-08-04
• Study Completion: 2022-08-04
• Results First Submitted: 2023-07-28
• Status Verified: 2023-09
• Results First Submitted QC: 2023-09-15
• Last Update Submitted: 2023-09-15
• Results First Posted: 2023-10-10
• Last Update Posted: 2023-10-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 133

Inclusion Criteria

• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• For obinutuzumab + polatuzumab vedotin + venetoclax treatment group, relapsed or refractory FL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-cluster of differentiation 20 (CD20) (anti-CD20) monoclonal antibody (mAb) and for which no other more appropriate treatment option exists, as determined by the investigator
• For rituximab + polatuzumab vedotin + venetoclax treatment group, relapsed or refractory DLBCL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-CD20 mAb and for which no curative option exists as determined by the investigator
• At least one bidimensionally measurable lesion

Exclusion Criteria

• Known CD20-negative status at relapse or progression
• Prior allogeneic stem cell transplantation (SCT), or autologous SCT within 100 days prior to Day 1 of Cycle 1
• Grade 3b FL
• History of transformation of indolent disease to DLBCL
• Current use of systemic corticosteroids greater than (>) 20 mg prednisone per day (or equivalent); or prior anti-cancer therapy to include: radioimmunoconjugate within 12 weeks; mAb or antibody-drug conjugate within 4 weeks; or radiotherapy/chemotherapy/hormone therapy/targeted small-molecule therapy within 2 weeks prior to Day 1 of Cycle 1
• Central nervous system (CNS) disease
• Active infection
• Actual or potential cytochrome P450 (CYP) 3A interactions including: requirement for warfarin; use of strong and moderate CYP3A inhibitors or inducers within 7 days prior to first dose of venetoclax; or consumption of grapefruit, Seville oranges, or star fruit within 3 days prior to first dose of venetoclax
• Positive for human immunodeficiency virus (HIV) or hepatitis B or C
• Receipt of a live virus vaccine within 28 days prior to Day 1 of Cycle 1
• Poor hematologic, renal, or hepatic function
• Pregnant or lactating women
• Life expectancy <3 months

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dose-Escalation Cohort: FL	Polatuzumab Vedotin	Participants with relapsed or refractory FL will receive 18 weeks of induction treatment with polatuzumab vedotin and venetoclax at escalating doses to identify the recommended Phase 2 dose (RP2D) for polatuzumab vedotin and venetoclax when combined with a fixed dose of obinutuzumab. Those who achieve CR, PR, or SD at the EOI will be eligible to receive a 24-month maintenance regimen consisting of 8 months of venetoclax and 24 months of obinutuzumab.
Dose-Escalation Cohort: FL	Obinutuzumab	Participants with relapsed or refractory FL will receive 18 weeks of induction treatment with polatuzumab vedotin and venetoclax at escalating doses to identify the recommended Phase 2 dose (RP2D) for polatuzumab vedotin and venetoclax when combined with a fixed dose of obinutuzumab. Those who achieve CR, PR, or SD at the EOI will be eligible to receive a 24-month maintenance regimen consisting of 8 months of venetoclax and 24 months of obinutuzumab.
Dose-Escalation Cohort: FL	Venetoclax	Participants with relapsed or refractory FL will receive 18 weeks of induction treatment with polatuzumab vedotin and venetoclax at escalating doses to identify the recommended Phase 2 dose (RP2D) for polatuzumab vedotin and venetoclax when combined with a fixed dose of obinutuzumab. Those who achieve CR, PR, or SD at the EOI will be eligible to receive a 24-month maintenance regimen consisting of 8 months of venetoclax and 24 months of obinutuzumab.
Dose-Escalation Cohort: DLBCL	Rituximab	Participants with relapsed or refractory DLBCL will receive 18 weeks of induction treatment. Venetoclax will be administered at escalating doses to identify the RP2D of venetoclax when combined with fixed doses of polatuzumab vedotin and rituximab. Those who achieve CR or PR at the EOI will be eligible to receive an 8-month consolidation regimen consisting of venetoclax and rituximab.
Dose-Escalation Cohort: DLBCL	Polatuzumab Vedotin	Participants with relapsed or refractory DLBCL will receive 18 weeks of induction treatment. Venetoclax will be administered at escalating doses to identify the RP2D of venetoclax when combined with fixed doses of polatuzumab vedotin and rituximab. Those who achieve CR or PR at the EOI will be eligible to receive an 8-month consolidation regimen consisting of venetoclax and rituximab.
Dose-Escalation Cohort: DLBCL	Venetoclax	Participants with relapsed or refractory DLBCL will receive 18 weeks of induction treatment. Venetoclax will be administered at escalating doses to identify the RP2D of venetoclax when combined with fixed doses of polatuzumab vedotin and rituximab. Those who achieve CR or PR at the EOI will be eligible to receive an 8-month consolidation regimen consisting of venetoclax and rituximab.
Expansion Cohort: FL	Obinutuzumab	Participants with relapsed or refractory FL will receive 18 weeks of induction treatment with polatuzumab vedotin and venetoclax at the RP2D identified during the dose-escalation phase, in addition to obinutuzumab. Those who achieve CR, PR, or SD at the EOI will be eligible to receive a 24-month maintenance regimen consisting of 8 months of venetoclax and 24 months of obinutuzumab.
Expansion Cohort: FL	Polatuzumab Vedotin	Participants with relapsed or refractory FL will receive 18 weeks of induction treatment with polatuzumab vedotin and venetoclax at the RP2D identified during the dose-escalation phase, in addition to obinutuzumab. Those who achieve CR, PR, or SD at the EOI will be eligible to receive a 24-month maintenance regimen consisting of 8 months of venetoclax and 24 months of obinutuzumab.
Expansion Cohort: FL	Venetoclax	Participants with relapsed or refractory FL will receive 18 weeks of induction treatment with polatuzumab vedotin and venetoclax at the RP2D identified during the dose-escalation phase, in addition to obinutuzumab. Those who achieve CR, PR, or SD at the EOI will be eligible to receive a 24-month maintenance regimen consisting of 8 months of venetoclax and 24 months of obinutuzumab.
Expansion Cohort: DLBCL	Polatuzumab Vedotin	Participants with relapsed or refractory DLBCL will receive 18 weeks of induction treatment. Venetoclax will be administered at the RP2D identified during the dose-escalation phase, in addition to polatuzumab vedotin and rituximab. Those who achieve CR or PR at the EOI will be eligible to receive an 8-month consolidation regimen consisting of venetoclax and rituximab.
Expansion Cohort: DLBCL	Rituximab	Participants with relapsed or refractory DLBCL will receive 18 weeks of induction treatment. Venetoclax will be administered at the RP2D identified during the dose-escalation phase, in addition to polatuzumab vedotin and rituximab. Those who achieve CR or PR at the EOI will be eligible to receive an 8-month consolidation regimen consisting of venetoclax and rituximab.
Expansion Cohort: DLBCL	Venetoclax	Participants with relapsed or refractory DLBCL will receive 18 weeks of induction treatment. Venetoclax will be administered at the RP2D identified during the dose-escalation phase, in addition to polatuzumab vedotin and rituximab. Those who achieve CR or PR at the EOI will be eligible to receive an 8-month consolidation regimen consisting of venetoclax and rituximab.

Primary Outcome Measures

Name	Time	Method
RP2D of Venetoclax	Day 1 of Cycle 1 to Day 1 of Cycle 2 (1 cycle=21 days) in dose-escalation phase	RP2D was defined as the highest dose with acceptable toxicity as determined from dose-escalation phase. The RP2D of venetoclax when given in combination with fixed dose of polatuzumab vedotin in participants with FL and DLBCL was determined.
DLBCL Cohorts: Percentage of Participants With AEs and SAEs	From study start to 3 months after last dose of study drug (approximately 21 months)	An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any new disease or worsening of an existing disease were also considered as AEs. An SAE was defined as any AE that was fatal, life threatening, requires prolonged inpatient hospitalization, resulted in significant disability or resulted in a congenital anomaly to a mother exposed to study treatment. AEs and SAEs were reported based on the NCI-CTCAE, v4.0. Percentages have been rounded off to the first decimal point.
Number of Participants With Dose-Limiting Toxicities (DLTs)	Day 1 of Cycle 1 to Day 1 of Cycle 2 (1 cycle=21 days) in dose-escalation phase	DLT=any one of the events that occurred in first treatment cycle \& per the investigator was related to study treatment. Any AE that lead to a delay of \> 14 days in start of next treatment cycle; Any Grade 3/4 non-hematologic AE with few exceptions; Any increase in hepatic transaminase \>3×baseline(BL) \& increase in direct bilirubin \>2×upper limit of normal (ULN), without any findings of cholestasis/jaundice/signs of hepatic dysfunction \& in absence of other contributory factors; Grade1 alanine transaminase (ALT)/aspartate transaminase (AST) elevation at BL as result of liver metastases, only a Grade ≥3 elevation, also ≥3×BL lasting \>7 days; Hematologic AE meeting protocol specified criteria. Events were graded per NCI CTCAE v4.0. Grade 1:Mild; asymptomatic/mild symptoms; Grade 2:Moderate;minimal,local/non-invasive intervention indicated; Grade 3:Severe/medically significant, but not immediately life-threatening; Grade 4:Life-threatening consequences/urgent intervention indicated.
RP2D of Polatuzumab Vedotin	Day 1 of Cycle 1 to Day 1 of Cycle 2 (1 cycle=21 days) in dose-escalation phase	RP2D was defined as the highest dose with acceptable toxicity as determined from dose-escalation phase. The RP2D of polatuzumab vedotin when given in combination with fixed dose of obinutuzumab in participants with FL was determined.
Percentage of Participants With CR at EOI Determined by an Independent Review Committee (IRC) on the Basis of Positron Emission Tomography (PET) and Computed Tomography (CT) Scans	6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21 days)	CR at EOI was assessed by the IRC according to modified Lugano Response Criteria (MLRC) for Malignant Lymphoma 2014 using PET-CT scan. Per MLRC, CR was defined as complete metabolic response (MR) in lymph nodes and extra lymphatic sites (ELS) with a score of 1, 2, or 3, with or without a residual mass on PET 5-point scale (5-PS), where 1=no uptake above background; 2= uptake ≤mediastinum; 3= uptake \> mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions. No new lesions; no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. 90% confidence interval (CI) for percentage of responders was calculated using Clopper-Pearson method. Percentages have been rounded off to the first decimal point.
FL Cohorts: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	From study start to 24 months after last dose of study drug (approximately 56 months)	An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any new disease or worsening of an existing disease were also considered as AEs. An SAE was defined as any AE that was fatal, life threatening, requires prolonged inpatient hospitalization, resulted in significant disability or resulted in a congenital anomaly to a mother exposed to study treatment. AEs and SAEs were reported based on the National Cancer Institute Common Terminology Criteria for AEs, version 4.0 (NCI-CTCAE, v4.0). Percentages have been rounded off to the first decimal point.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With CR at EOI, Determined by the Investigator on the Basis of CT Scans Alone	6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)	CR at EOI was determined by Investigator according to the MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease; organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. 90% CI for percentage of responders was calculated using Clopper-Pearson method.
Percentage of Participants With OR at EOI, Determined by the Investigator on the Basis of PET and CT Scans	6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)	OR=percentage of participants with CR or PR as assessed by the IRC according to MLRC. Per MLRC CR based on PET-CT=complete MR in lymph nodes \& ELS with score of 1, 2, or 3 with or without residual mass on 5PS, where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake\> mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions;no new lesions \& no evidence of FDG-avid disease in bone marrow. PR based on PET-CT=partial MR in lymph nodes \& ELS with score of 4 or 5 with reduced uptake compared with baseline \& residual masses of any size: at interim (suggest responding disease) or at end of treatment (indicate residual disease), residual uptake higher than uptake in normal bone marrow but reduced compared with baseline (diffuse uptake compatible with reactive changes from chemotherapy allowed). 90% CI was calculated using Clopper-Pearson method. Percentages have been rounded off to the first decimal point.
Observed Serum Obinutuzumab Concentration	Pre-dose & 0.5 hours post-dose on Day 1 Cycles 1, 2, 4, & 6; and pre-dose on Day 1 of Months 2, 8, 14, 20; study drug discontinuation, Day 120 &1 year post-last dose (up to approximately 40 months) (1 cycle = 21 days)
Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE)	Pre-dose and 0.5 hours post-dose on Day 1 of Cycles 1, 2 and 4; post-dose on Days 8 and 15 of Cycle 1; predose on Day 1 of Cycle 6 (1 cycle=21 days)	acMMAE is an analyte of polatuzumab vedotin.
Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE	Pre-dose and 0.5 hours post-dose on Day 1 of Cycles 1, 2 and 4; post-dose on Days 8 and 15 of Cycle 1; predose on Day 1 of Cycle 6 (1 cycle=21 days)	MMAE is an analyte of polatuzumab vedotin.
Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin	Pre-dose on Day 1 of Cycles 1, 2 and 4; study drug discontinuation visit; Day 120 and 1 year post-last dose (up to approximately 16 months) (1 cycle=21 days)	Total antibody is an analyte of polatuzumab vedotin.
Percentage of Participants With OR at EOI, Determined by the Investigator on the Basis of CT Scans Alone	6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)	OR was defined as the percentage of participants with CR or PR, as assessed by the investigator based on MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease; organ enlargement regressing to normal; no new lesions; bone marrow normal by morphology, if indeterminate, IHC negative. PR per CT only was defined as partial remission in lymph nodes and ELS with ≥50% decrease in the SPD of up to 6 target measurable lymph nodes and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal, no new sites of lesions. 90% CI for percentage of responders was calculated using Clopper-Pearson method. Percentages have been rounded off to the first decimal point.
Observed Serum Rituximab Concentration	Pre-dose and 0.5 hours post-dose on Day 1 of Cycles 1 and 6; pre-dose on Day 1 of Cycles 2 and 4; (1 cycle = 21 days)
Percentage of Participants With CR at EOI, Determined by the Investigator on the Basis of PET-CT Scans	6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)	CR at EOI was assessed by Investigator according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass, on 5PS where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake \> mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions; no evidence of FDG-avid disease in bone marrow. 90% CI for percentage of responders was calculated using Clopper-Pearson method. Percentages have been rounded off to the first decimal point.
Percentage of Participants With CR at EOI, Determined by the IRC on the Basis of CT Scans Alone	6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)	CR at EOI was determined by IRC according to the MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 centimeters (cm) in longest transverse diameter (LDi) and no ELS of disease; organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, immunohistochemistry (IHC) negative. 90% CI for percentage of responders was calculated using Clopper-Pearson method. Percentages have been rounded off to the first decimal point.
Percentage of Participants With Objective Response (OR) at EOI, Determined by an IRC on the Basis of PET and CT Scans	6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)	OR=percentage of participants with CR or PR as assessed by the IRC according to MLRC. Per MLRC CR based on PET-CT=complete MR in lymph nodes \& ELS with score of 1, 2, or 3 with or without residual mass on 5PS, where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake\> mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions; no new lesions \& no evidence of FDG-avid disease in bone marrow. PR based on PET-CT=partial MR in lymph nodes \& ELS with score of 4 or 5 with reduced uptake compared with baseline \& residual masses of any size: at interim (suggest responding disease) or at end of treatment (indicate residual disease), residual uptake higher than uptake in normal bone marrow but reduced compared with baseline (diffuse uptake compatible with reactive changes from chemotherapy allowed). 90% CI was calculated using Clopper-Pearson method. Percentages have been rounded off to the first decimal point.
Percentage of Participants With OR at EOI, Determined by an IRC on the Basis of CT Scans Alone	6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)	OR was defined as the percentage of participants with CR or PR, as assessed by the IRC based on MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease; organ enlargement regressing to normal; no new lesions; bone marrow normal by morphology, if indeterminate, IHC negative. PR per CT only was defined as partial remission in lymph nodes and ELS with ≥50% decrease in the sum of the products of greatest diameters (SPD) of up to 6 target measurable lymph nodes and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal, no new sites of lesions. 90% CI for percentage of responders was calculated using Clopper-Pearson method. Percentages have been rounded off to the first decimal point.
Percentage of Participants With Best Overall Response (BOR) of CR or PR, Determined by the Investigator on the Basis of CT Scans Alone	Up to every 6 months until disease progression, the start of new anti-lymphoma treatment, or the end of the study, whichever occurs first (approximately 77 months)	BOR=CR or PR as assessed by investigator per CT per MLRC. Per MLRC, CR based on CT was defined as a complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease; organ enlargement regressing to normal; no new lesions; bone marrow normal by morphology, if indeterminate, IHC negative. PR per CT only was defined as partial remission in lymph nodes and ELS with ≥50% decrease in SPD of up to 6 target measurable lymph nodes and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal, no new sites of lesions. Percentages have been rounded off to the first decimal point.
Observed Plasma Venetoclax Concentration	Pre-dose and 4 hours post-dose on Day 1 Cycle 1, pre-dose & 2, 4, 6, & 8 hours post-dose on Day 1 Cycle 2, pre-dose & 4hours post-dose on Day 1 Cycle 4 & pre-dose on Day 1 Cycle 6; (1 cycle = 21 days)
Number of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab	Baseline up to approximately 2 years after last dose (up to approximately 56 months)	The number of participants with positive results for HAHAs, also called anti-drug antibodies (ADAs) against obinutuzumab at baseline and at any of the post-baseline assessment time-points were reported. Number of participants positive for Treatment Emergent ADA = the number of post-baseline evaluable participants determined to have treatment induced ADA or treatment-enhanced ADA during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 titer unit (t.u.) greater than the baseline titer result.
Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Polatuzumab Vedotin	Baseline up to 1 year post last dose (up to approximately 16 months)	The number of participants with positive results for ATAs, also called ADAs against polatuzumab vedotin at baseline and at any of the post-baseline assessment time-points were reported. Number of participants positive for Treatment Emergent ADA = the number of post-baseline evaluable participants determined to have treatment induced ADA or treatment-enhanced ADA during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 t.u. greater than the baseline titer result.

Trial Locations

Locations (23)

Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori; 🇮🇹 Meldola, Emilia-Romagna, Italy

Fondazione IRCCS Istituto Nazionale dei Tumori; 🇮🇹 Milano, Lombardia, Italy

SCDU Ematologia; 🇮🇹 Novara, Piemonte, Italy

Calvary Mater Newcastle; 🇦🇺 Waratah, New South Wales, Australia

Papa Giovanni Hospital XXIII; 🇮🇹 Bergamo, Emilia-Romagna, Italy

Scott and White; 🇺🇸 Temple, Texas, United States

Roswell Park Cancer Inst.; 🇺🇸 Buffalo, New York, United States

Royal North Shore Hospital; Haematology Department; 🇦🇺 St. Leonards, New South Wales, Australia

Princess Alexandra Hospital; 🇦🇺 Woolloongabba, Queensland, Australia

A.O.U. Citta' Della Salute E Della Scienza-P.O. Molinette;S.C. Ematologia; 🇮🇹 Torino, Piemonte, Italy

Fox Chase Cancer Center; 🇺🇸 Philadelphia, Pennsylvania, United States

Royal Hobart Hospital; 🇦🇺 Hobart, Tasmania, Australia

University of Arizona Cancer Center; 🇺🇸 Tucson, Arizona, United States

Rutgers Cancer Institute of New Jersey; 🇺🇸 New Brunswick, New Jersey, United States

Peter MacCallum Cancer Center; 🇦🇺 North Melbourne, Victoria, Australia

Emory Univ Winship Cancer Inst; 🇺🇸 Atlanta, Georgia, United States

Ospedale Infermi U.O. Ematologia; 🇮🇹 Rimini, Emilia-Romagna, Italy

UO Ematologia, Ospedale S.Maria delle Croci; 🇮🇹 Ravenna, Emilia-Romagna, Italy

The Queen Elizabeth Hospital; 🇦🇺 Adelaide, South Australia, Australia

Yale Cancer Center; 🇺🇸 New Haven, Connecticut, United States

University of Louisville Hospital; The James Graham Brown Cancer Center; 🇺🇸 Louisville, Kentucky, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Memorial Healthcare System; 🇺🇸 Pembroke, Florida, United States