A Trial In Patients With Advanced Cancer And Leukemia
- Registration Number
- NCT00878189
- Lead Sponsor
- Pfizer
- Brief Summary
This is a phase 1, dose escalating study to determine the safety of PF-03084014 in patients with advanced cancer and leukemia
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 72
- Patients with advanced cancer that is resistant to standard therapy or for which no standard therapy is available
- Patients with acute T cell leukemia/lymphoblastic lymphoma that is resistant to standard therapy or for which no standard therapy is available
- Men and women >16 years old
- Prior treatment with a gamma secretase inhibitor for treatment of cancer
- Patients taking Tamoxifen
- Patients with active graft versus host disease
- Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
- Patients who are pregnant or breast feeding
- Patients with clinical evidence of central nervous system disease
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description 1 PF-03084014 -
- Primary Outcome Measures
Name Time Method Number of Solid Tumor Participants With First-Cycle Dose-Limiting Toxicity (DLT) Baseline to the end of Cycle 1 (Week 4) Any DLT event attributable to PF-03084014 during Cycle 1: non-hematologic toxicities \>= Grade 3 despite optimal care; treatment delay \>=7 days or unable to deliver at least 80% of planned dose due to treatment-related toxicities; Grade 4 neutropenia \>7 days; febrile neutropenia; neutropenic infection; Grade \>=3 thrombocytopenia with bleeding
Number of T-ALL/LBL Participants With First-Cycle DLT Baseline to the end of Cycle 1 (Week 4) Any DLT attributable to PF-03084014 at 1st Cycle: non-hematologic toxicities \>= Grade 3 despite optimal care; treatment delay \>=7 days; unable to deliver at least 80% of planned dose; absolute neutrophil count (ANC) \<1000/microliter (uL), or platelet count \<30,000/uL, or hemoglobin \<8 gram/deciliter (g/dL) in a bone marrow with \<5% blasts and no evidence of leukemia or abnormal dysplasia for \>42 days
- Secondary Outcome Measures
Name Time Method Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causality) by Severity (by Maximum Common Terminology Criteria for Adverse Events [CTCAE] Grade) Baseline up to end of study (maximum of 84 months) An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent were events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. CTCAE version 3.0 was used for AE grading: Grade 1 mild AE; Grade 2 moderate AE; Grade 3 severe AE; Grade 4 life-threatening or disabling AE; Grade 5 death related to AE.
Number of Participants With TEAEs (Treatment-Related) by Severity (by Maximum CTCAE Grade) Baseline up to end of study (maximum of 84 months) An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-related events were those assessed by the investigator as related to study medication. CTCAE version 3.0 was used for AE grading: Grade 1 mild AE; Grade 2 moderate AE; Grade 3 severe AE; Grade 4 life-threatening or disabling AE; Grade 5 death related to AE.
Dose-normalized Cmax [Cmax (dn)] After a Single Dose on Cycle 1 Day 1 Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, and 10 hr post-dose) Cmax(dn) was calculated by maximum observed serum concentration (Cmax) divided by administered dose.
Cmax After Multiple Dose on Cycle 1 Day 21 Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose) Cmax was the maximum observed serum concentration. Cycle 1 Day 21 PK parameter summaries are presented only for participants who were considered to be dose compliant. CV is the coefficient of variation.
AUCtau After Multiple Dose on Cycle 1 Day 21 Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose) AUCtau was area under the serum concentration-time profile from time 0 to tau (dosing interval). Cycle 1 Day 21 PK parameter summaries are presented only for participants who were considered to be dose compliant.
Apparent Oral Clearance (CL/F) on Cycle 1 Day 21 Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose) Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Cycle 1 Day 21 PK parameter summaries are presented only for participants who were considered to be dose compliant.
Minimum Observed Serum Concentration (Cmin) After Multiple Dose on Cycle 1 Day 21 Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose) Cmin was the minimum serum concentration. Cycle 1 Day 21 PK parameter summaries are presented only for participants who were considered to be dose compliant.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causality) Baseline up to end of study (maximum of 84 months) An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of casual relationship. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. A serious adverse event (SAE) was any untoward medical occurrence at any dose that: resulted in death, was life-threatening (immediate risk of death), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions), and resulted in congenital anomaly/birth defect.
Number of Participants With Potentially Clinical Significant Categorical Changes From Baseline in Electrocardiogram (ECG) Findings in QTc Interval Baseline up to end of study (maximum of 84 months) Criteria for potentially important changes in ECG were defined as: maximum (max.) post-dose (post-baseline) time from electrocardiogram Q wave to the corresponding to electrical systole (QT interval) corrected for Fridericia's factor (QTcF), or QT interval corrected for Bazett's factor (QTcB): \<450, 450 -\<480, 480-\<500, and \>=500 msec. Maximum increase (inc.) from baseline in QTcF or QTcB: change (chg) \<30, 30\>=chg\<60, and chg \>=60 msec.
Time to Reach Cmax (Tmax) After a Single Dose on Cycle 1 Day 1 Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, and 10 hr post-dose) Tmax was the time to reach maximum serum concentration (Cmax).
Average Serum Concentration (Cavg) at Steady State on Cycle 1 Day 21 Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose) Cavg was the average serum concentration at steady state. Cycle 1 Day 21 PK parameter summaries are presented only for participants who were considered to be dose compliant.
Maximum Observed Serum Concentration (Cmax) After a Single Dose on Cycle 1 Day 1 Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, and 10 hr post-dose) Cmax was the maximum observed serum concentration.
Area Under the Time-Concentration Curve From Time 0 to the Dosing Interval (AUCtau) After a Single Dose on Cycle 1 Day 1 Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, and 10 hr post-dose) AUCtau was area under the serum concentration-time profile from time 0 to tau (dosing interval). CV is the coefficient of variation.
Dose-normalized AUCtau [AUCtau (dn) ] After a Single Dose on Cycle 1 Day 1 Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, and 10 hr post-dose) AUCtau (dn) was calculated by area under the serum concentration-time profile from time 0 to tau (dosing interval) (AUCtau) divided by administered dose. NE is not estimable.
Serum Decay Half-Life (t1/2) After Multiple Dose on Cycle 1 Day 21 Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose) Serum decay half-life (t1/2) is the time measured for the serum concentration to decrease by one half. Cycle 1 Day 21 PK parameter summaries are presented only for participants who were considered to be dose compliant.
Accumulation Ratio (Rac) on Cycle 1 Day 21 Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, and 10 hr post-dose), Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose) Accumulation was calculated as AUCtau at steady state (Cycle 1 Day 21) divided by AUCtau after a single dose on Cycle 1 Day 1. Cycle 1 Day 21 PK parameter summaries are presented only for participants who were considered to be dose compliant.
AUCtau in the Fed State for Solid Tumor Participants Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) or Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) AUCtau was area under the serum concentration-time profile from time 0 to tau (dosing interval).
Cmax in the Fasted State for Solid Tumor Participants Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) or Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) Cmax was the maximum observed serum concentration.
Dose-normalized AUCtau [AUCtau(dn)] in the Fasted State for Solid Tumor Participants Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) or Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) AUCtau(dn) was calculated by area under the serum concentration-time profile from time 0 to tau (dosing interval) (AUCtau) divided by administered dose.
Dose-normalized Cmax [Cmax(dn)] in the Fasted State for Solid Tumor Participants Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) or Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) Cmax(dn) was calculated by maximum observed serum concentration (Cmax) divided by administered dose.
Number of Participants With TEAEs (Treatment-Related) Baseline up to end of study (maximum of 84 months) An AE was any untoward medical occurrence in a participant who received study drug. Treatment-related events were those assessed by the investigator as related to study medication. An SAE was any untoward medical occurrence at any dose that: resulted in death, was life-threatening (immediate risk of death), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions), and resulted in congenital anomaly/birth defect.
AUCtau on Cycle 2 Day 1 Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) AUCtau was area under the serum concentration-time profile from time 0 to tau (dosing interval). Data for this outcome measure was planned to be analyzed for two arms only.
Dose-normalized Cmax [Cmax (dn)] on Cycle 2 Day 1 Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) Cmax(dn) was calculated by maximum observed serum concentration (Cmax) divided by administered dose. Data for this outcome measure was planned to be analyzed for two arms only.
Number of Participants With Laboratory Tests Abnormalities Meeting the Criteria of Potential Clinical Concern (Hematology and Chemistries, All Cycles) Baseline up to end of study (maximum of 84 months) Parameters analyzed included: white blood cell (WBC) count plus differential, absolute (abs) neutrophil count, platelets, hemoglobin, sodium, potassium, bicarbonate, chloride, blood urea nitrogen, creatinine, glucose, uric acid, calcium, phosphate, magnesium, total protein, albumin, total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), partial prothrombin time/international normalized ratio (PTT/INR). Urinalysis: pH, specific gravity, protein, glucose, ketones, blood, leukocyte esterase, and nitrites. Pregnancy test: Serum or urine pregnancy test for women of childbearing potential. There were no changes in urine protein among the solid tumor and T-ALL/LBL participants that were clinically significant. Clinical significance was judged by the investigator.
Time to Reach Cmax (Tmax) After Multiple Dose on Cycle 1 Day 21 Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose) Tmax was the time to reach maximum serum concentration (Cmax). Cycle 1 Day 21 PK parameter summaries are presented only for participants who were considered to be dose compliant.
Apparent Volume of Distribution (Vz/F) on Cycle 1 Day 21 Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose) Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired concentration of a drug. Cycle 1 Day 21 PK parameter summaries are presented only for participants who were considered to be dose compliant.
Dose-normalized Cmax [Cmax (dn)] After Multiple Dose on Cycle 1 Day 21 Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose) Cmax(dn) was calculated by maximum observed serum concentration (Cmax) divided by administered dose. Cycle 1 Day 21 PK parameter summaries are presented only for participants who were considered to be dose compliant.
AUCtau in the Fasted State for Solid Tumor Participants Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) or Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) AUCtau was area under the serum concentration-time profile from time 0 to tau (dosing interval).
Cmax in the Fed State for Solid Tumor Participants Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) or Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) Cmax was the maximum observed serum concentration.
Time to Tumor Progression (TTP) for Solid Tumor Participants Baseline until first documented objective progression (up to maximum of 84 months) Time from Cycle 1 Day 1 to first documentation of disease progression. Progression was defined as per RECIST version 1.0, as a 20% increase in the sum of the longest diameter of target lesions, or target lesions over nadir, uneuivocal progression of non-target disease, or the appearance of new lesions. TTP (months) was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 30.
Progression-Free Survival (PFS) for Solid Tumor Participants Baseline, Cycle 2 Day 1, Cycle 3 Day 1 and then Day 1 (+ or - 5 days) of every odd cycle or as clinically indicated, up to Cycle 9; afterwards assessed on Day 1 (+ or -5 days) every 4 cycles (up to maximum of 84 months) PFS was defined as the time from Cycle 1 Day 1 to date of first documentation of progression or death due to any cause. Progression was defined as per RECIST version 1.0, as a 20% increase in the sum of the longest diameter of target lesions, or target lesions over nadir, unequivocal progression of non-target disease, or the appearance of new lesions. PFS (months) was calculated as (the first event date minus the date of first dose of study medication plus 1) divided by 30.
Dose-normalized AUCtau [AUCtau (dn)] After Multiple Dose on Cycle 1 Day 21 Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose) AUCtau (dn) was calculated by area under the serum concentration-time profile from time 0 to tau (dosing interval) (AUCtau) divided by administered dose. Cycle 1 Day 21 PK parameter summaries are presented only for participants who were considered to be dose compliant.
Dose-normalized AUCtau [AUCtau(dn)] in the Fed State for Solid Tumor Participants Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) or Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) AUCtau(dn) was calculated by area under the serum concentration-time profile from time 0 to tau (dosing interval) (AUCtau) divided by administered dose.
Percentage of T-ALL/LBL Participants With OR Baseline, Cycle 2 Day 1, Cycle 3 Day 1 and then Day 1 (+ or - 5 days) of every odd cycle or as clinically indicated, up to Cycle 9 (up to maximum of 84 months) OR was adapted from International Working Group Response Criteria for Acute Myeloid Leukemia (AML). The response categories of interest were CR, complete response with incomplete hematopoietic recovery (CRi), and PR. CR: ANC \>1500/microliter (uL), no circulating blasts. Platelets \>100,000/uL, \<5% marrow blast cells, no extramedullary disease, bone marrow cellularity \>20% with tri-lineage hematopoiesis and \<5% marrow blast cells, none of which were neoplastic; CRi: same as CR but ANC may be \>1500/uL or platelet count \>100,000/uL, no requirement on bone marrow cellularity; PR: same as CR but bone marrow with \>= 50% reduction of leukemia blast cells and an absolute blast count between 5% and 25%.
Changes in Expression Levels of Notch 1 Target Genes in Peripheral Blood for Solid Tumor Participants: Hes4 Gene Expression Level on Cycle 1 Day 8 and Cycle 1 Day 21 Relative to That at Baseline Baseline (morning), Cycle 1 Days 8 and 21 (pre-dose) Ribonucleic acid (RNA) was extracted from peripheral blood and used as a template to synthesize complementary deoxyribonucleic acid (cDNA). Gene expression in cDNA was measured by custom Taqman low density array (TLDA) cards run on Applied Biosystems 7900HT Fast Real-Time polymerase chain reaction (PCR) system. Changes from baseline were calculated as ratios to baseline. Results were reported Only for Hes4 as this was the only gene to show consistent down modulation across dosing cohorts (150 mg and 220 mg).
Dose-Normalized Cmax [Cmax(dn)] in the Fed State for Solid Tumor Participants Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) or Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose). Cmax(dn) was calculated by maximum observed serum concentration (Cmax) divided by administered dose.
Dose-normalized AUCtau [AUCtau (dn)] on Cycle 2 Day 1 Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) AUCtau(dn) was calculated by area under the serum concentration-time profile from time 0 to tau (dosing interval) (AUCtau) divided by administered dose. Data for this outcome measure was planned to be analyzed for two arms only.
Cmax on Cycle 2 Day 1 Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) Cmax was the maximum observed serum concentration. Data for this outcome measure was planned to be analyzed for two arms only.
Tmax on Cycle 2 Day 1 Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) Tmax was the time to reach maximum serum concentration (Cmax). Data for this outcome measure was planned to be analyzed for two arms only.
Relapse Free Survival (RFS) for T-ALL/LBL Participants Baseline, Cycle 2 Day 1, Cycle 3 Day 1 and then Day 1 (+ or - 5 days) of every odd cycle or as clinically indicated, up to Cycle 9 (up to maximum of 84 months) The RFS of CR was defined as the time from the date of first attaining CR to the date of relapse or death from any cause, whichever occurred first. Similarly, the RFS of CR + CRi (or RFS of CR + CRi + PR) was defined as the time from the date of first attaining CR + CRi (or CR + CRi + PR) to the date of relapse or death from any cause, whichever occurred first.
Changes From Baseline in Notch Intracellular Domain (NICD) Levels in Bone Marrow for T-ALL/LBL Participants Baseline, Cycle 1 Day 1 and Cycle 2 Day 1 Notch intracellular domain (NICD) was to be measured in bone marrow monoculear cell (BMMC) cell pellets using a validated ELISA.
Percentage of Solid Tumor Participants With Objective Response (OR) Baseline, Cycle 2 Day 1, Cycle 3 Day 1 and then Day 1 (plus [+] or minus [-] 5 days) of every odd cycle or as clinically indicated, up to Cycle 9; afterwards assessed on Day 1 (+ or -5 days) every 4 cycles Objective response (OR) was defined as confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0). Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as \>=30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study \>=4 weeks after initial documentation of response.
Duration of Response (DR) for Solid Tumor Participants Baseline, Cycle 2 Day 1, Cycle 3 Day 1 and then Day 1 (+ or -5 days) of every odd cycle or as clinically indicated, up to Cycle 9. Afterwards, assessed on Day 1 (+ or -5 days) every 4 cycles (up to maximum of 84 months) Time from the first documentation of OR to objective disease progression or death due to any cause. DR was only calculated for participants with an OR. DR (months) was calculated as (date of first documentation of objective progression or death minus date of first documentation of PR or CR plus 1) divided by 30.
Changes in Expression Levels of Notch 1 Target Genes in Tumor Biopsies for Solid Tumor Participants: Hairy and Enhancer of Split-4 (Hes4) Gene Expression Levels on Cycle 1 Day 21 Relative to That at Baseline Baseline, Cycle 1 Day 21 (-5 days) Gene expression analysis in tumor biopsies was done using cDNA prepared from RNA extracted from tumor biopsies. Gene expression was measured by custom Taqman low density array (TLDA) cards run on Applied Biosystems 7900HT Fast Real-Time polymerase chain reaction (PCR) system. Changes from baseline were calculated as ratios to baseline. Only Hes4 gene showed consistent down modulation across dosing cohorts (150 mg and 220 mg BID) and therefore results were reported for Hes4 only. Data for this outcome measure was planned to be analyzed for two arms only.
Changes From Baseline in Notch Intracellular Domain (NICD) Levels in Peripheral Blood for T-ALL/LBL Participants Baseline, Cycle 1 Days 8 and 15 (pre-dose AM), Cycle 1 Day 21 (pre-dose AM and 24, 48 and 120 hr post-dose) and end of treatment (EOT). Notch intracellular domain (NICD) levels was measured in peripheral blood mononuclear cell (PBMC) pellets using a validated enzyme-linked immunosorbent assay (ELISA).
Peripheral Blast Count Reduction (PBR) for T-ALL/LBL Participants Baseline, Cycle 2 Day 1, Cycle 3 Day 1 and then Day 1 (+ or - 5 days) of every odd cycle or as clinically indicated, up to Cycle 9 (up to maximum of 84 months) PBR was the maximum percentage of peripheral blast count reduction for each participant who received at least one dose of study medication. PBR was derived by the Sponsor from percentage of peripheral blood Blast Count reported by sites.
Changes From Baseline in Expression Levels of Notch 1 Target Genes in Peripheral Blood for T-ALL/LBL Participants: Hes4 Gene Expression Levels on Cycle 1 Day 8, Cycle 1 Day 15, Cycle 1 Day 21 Relative to That at Baseline Baseline (morning), Cycle 1 Days 8, 15 and 21 (morning, matched with the first PK sample of the particular day), Cycle 1 Day 21 (24, 48, and 120 hr post-dose) and at end of treatment (EOT) Ribonucleic acid (RNA) was extracted from peripheral blood and used as a template to synthesize complementary deoxyribonucleic acid (cDNA). Gene expression in cDNA was measured by custom Taqman low density array (TLDA) cards run on Applied Biosystems 7900HT Fast Real-Time polymerase chain reaction (PCR) system. Changes from baseline were calculated as ratios to baseline. Results were reported Only for Hes4 as this was the only gene to show consistent down modulation across dosing cohorts (150 mg and 220 mg).
Trial Locations
- Locations (10)
Massachusetts General Hospital Clinical Laboratory
🇺🇸Boston, Massachusetts, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
DIPRTMNT CLIN Scienze RADIOL e Istocitopatologiche
🇮🇹Bologna, Italy
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Karmanos Cancer Center / Wayne State University
🇺🇸Detroit, Michigan, United States
Dana Ferber Cancer institute
🇺🇸Boston, Massachusetts, United States
Anschutz Cancer Pavilion
🇺🇸Aurora, Colorado, United States
University of Colorado Hospital
🇺🇸Aurora, Colorado, United States
University of Colorado Denver CTRC
🇺🇸Aurora, Colorado, United States
Istituto di Ematologia Seragnoli
🇮🇹Bologna, Italy