A Study Of PF-06747143, As Single Agent Or In Combination With Standard Chemotherapy In Adult Patients With Acute Myeloid Leukemia

Phase 1

Terminated

Conditions: Acute Myeloid Leukemia

Interventions: Biological: PF-06747143
Drug: Cytarabine
Drug: Azacitidine
Drug: Daunorubicin
Drug: Decitabine

Registration Number: NCT02954653

Lead Sponsor: Pfizer

Brief Summary: Two part, dose escalation and dose expansion study. Open label, multi center, non randomized, multiple dose, safety, pharmacokinetic and pharmacodynamic study of single agent PF-06747143 in sequential dose levels of adult patients with refractory or relapsed AML in order to establish maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D) or maximally permitted dose (MPD) following by a 3 arm dose expansion with PF-06747143 in combination with standard of care chemotherapy in adult patients with AML.

Detailed Description: Patients will receive intravenous (IV) PF-06747143 as a weekly infusion (QW) in 28 day cycles at escalating doses. The proposed dosing scheme includes 0.3, 1.0, 3.0, 10, 15, and 20 mg/kg. Patients will be monitored for dose limiting toxicity (DLT) in the dose escalation in order to define the MTD. Two of the three arms in the dose expansion will include PF-06747143 in combination with standard of care chemotherapy and will include a safety lead in. The third arm, pending clinical data, will be PF-06747143 as a single agent.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 8

Inclusion Criteria

Part 1 and Part 2 cohort 3: Patients diagnosed with AML ( bone marrow (BM) or peripheral blood (PB) blast counts >/= 20%) and have received prior chemotherapy and/or standard of care and have relapsed, refractory or Minimal Residual Disease (defined as patients showing residual blast 10-14 days post-induction chemotherapy).

• Patients that are not candidates to receive standard of care and/or refusing the standard care of therapies will also be considered.

Part 2 - Cohort 1 and 2: Newly diagnosed, previously untreated de novo or secondary AML population (AML with bone marrow or peripheral blast counts 20%):

Cohort 1: Fit to receive intensive remission induction chemotherapy.
Cohort 2: Unfit to receive or not considered a candidate for intensive remission induction chemotherapy.

Part 1 and 2:

Life expectancy at least 12 weeks.
Hydroxyurea is allowed on study to control total peripheral white blood cell count but must be ceased 24 hours prior to first dose.
Off of prior therapy for 2-4 weeks prior to first dose.
ECOG performance status: 0 to 2.
Resolved acute effects of any prior therapy.
Adequate renal and hepatic function.

Exclusion Criteria

Patients with acute promyelocytic leukemia, AML with known central nervous system (CNS) involvement unless the patient has completed treatment for the CNS disease, has recovered from the acute effects of therapy prior to study entry, and is neurologically stable.
Patient is known refractory to platelet or packed red cell transfusions per institutional guidelines.
Prior treatment with a compound targeting CXCR4.
Chronic systemic corticosteroid treatment.
Known or suspected hypersensitivity to recombinant human proteins.
Chronic graft versus host disease (GVHD), active GVHD with other than Grade 1 skin involvement, or GVHD requiring systemic immunosuppressive treatment (Part 1 and cohort 3).
Not recovered from stem cell transplant associated toxicities (Part 1 and cohort 3).
Prior treatment with hypomethylating agents or chemotherapy for antecedent myelodysplastic syndrome (MDS) (Part 2, cohort 2)
AML associated with favorable risk karyotypes, including inv(16), t(8;21), t(16;16), or t(15;17) (cohort 2)
Candidates for allogeneic stem cell transplant (Part 2, cohort 2)
Known hypersensitivity to cytarabine or daunorubicin (Part 2, cohort 1) and decitabine or azacitidine or mannitol (Part 2, cohort 2).

Study & Design

Study Type: INTERVENTIONAL

Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Dose Escalation	PF-06747143	Single agent PF-06747143 dose escalation
Cohort 1	PF-06747143	PF-06747143 with standard dose cytarabine and daunorubicin.
Cohort 1	Daunorubicin	PF-06747143 with standard dose cytarabine and daunorubicin.
Cohort 2	PF-06747143	PF-06747143 in combination with Azacitidine or Decitabine.
Cohort 3	PF-06747143	PF-06747143 dose expansion as a single agent.
Cohort 1	Cytarabine	PF-06747143 with standard dose cytarabine and daunorubicin.
Cohort 2	Azacitidine	PF-06747143 in combination with Azacitidine or Decitabine.
Cohort 2	Decitabine	PF-06747143 in combination with Azacitidine or Decitabine.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Dose-Limiting Toxicities (DLTs) [Part 1]	Day 1 to Day 28 of Cycle 1	DLTs were classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03 and were defined as any of a predefined set of unacceptable hematologic and non-hematologic adverse events (AEs) occurring in the first treatment cycle unless clearly determined unrelated to PF-06747143. In addition, clinically important or persistent toxicities that were not included in the pre-specified criteria could be considered a DLT following review by the investigators and sponsor.
Number of Participants With Treatment-Emergent Adverse Events (AEs) [Part 2]	1 year	An AE was any untoward medical occurrence in a participant administered a product or medical device without regard to possibility of causal relationship. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment.
Number of Participants With Laboratory Abnormalities [Part 2]	1 year	Following parameters were to be analyzed for laboratory examination: hematology (hemoglobin, platelets, white blood cell \[WBC\], absolute neutrophils, absolute lymphocytes, absolute monocytes, absolute eosinophils, absolute basophils, percent blast cells); chemistry (aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], alkaline phosphatase, sodium, potassium, magnesium, chloride, total calcium, total bilirubin, blood urea nitrogen or urea, creatinine, uric acid, glucose \[non-fasted\], albumin, phosphorous or phosphate); coagulation (prothrombin time \[PT\] or international normalized ratio \[INR\], partial thromboplastin time \[PTT\] or activated PTT \[aPTT\]); urinalysis (urine dipstick for urine protein: if positive collect 24 hours and microscopic \[reflex testing\]; urine dipstick for urine blood: if positive collect a microscopic \[reflex testing\]); pregnancy test (for female participants of childbearing potential, serum or urine).
Objective Response Rate (ORR) - Percentage of Participants With Objective Response [Part 2]	16 weeks	Objective Response was defined as morphologic leukemia-free state (MLFS), complete remission (CR), cytogenetic CR (CRc), molecular CR (CRm), partial remission (PR), or CR or PR with incomplete blood count recovery (CRi or PRi). MLFS: Bone marrow (BM) blasts \<5%; absence of blasts with Auer rods and extramedullary disease (EMD). CR: MLFS criteria; absolute neutrophil count (ANC)\>1000/ul and platelet \>100,000/ul; independence from red cell transfusions. CRc: Reversion to a normal karyotype at the time of CR in cases with an abnormal karyotype at the time of diagnosis; based on the evaluation of 20 metaphase cells from BM. CRm: Reversion to a molecular-negative phenotype at the time of CR. CRi: All CR criteria except for ANC \<1000/ul or platelet \<100,000/ul. PR: ANC \>1000/ul and platelet \>100,000/ul; BM blasts decreased to 5-25% and ≥50% decrease from pre-treatment levels. PRi: ANC \<1000/ul or platelet \<100,000/ul; BM blasts decreased to 5-25% and ≥50% decrease from pre-treatment levels.
Duration of Objective Response Rate (ORR) [Part 2]	16 weeks	Duration of ORR is the time from first documentation of MLFS, CR, CRc, CRm, PR, CRi or PRi to date of first documentation of disease progression or death due to any cause. MLFS: BM blasts \<5%; absence of blasts with Auer rods and EMD. CR: MLFS criteria; ANC\>1000/ul and platelet \>100,000/ul; independence from red cell transfusions. CRc: Reversion to a normal karyotype at the time of CR in cases with an abnormal karyotype at the time of diagnosis; based on the evaluation of 20 metaphase cells from BM. CRm: Reversion to a molecular-negative phenotype at the time of CR. CRi: All CR criteria except for ANC \<1000/ul or platelet \<100,000/ul. PR: ANC \>1000/ul and platelet \>100,000/ul; BM blasts decreased to 5-25% and ≥50% decrease from pre-treatment levels. PRi: ANC \<1000/ul or platelet \<100,000/ul; BM blasts decreased to 5-25% and ≥50% decrease from pre-treatment levels. Disease progression/relapse: BM blast ≥5%; or reappearance of blast in the blood; or development of EMD.
Progression Free Survival [Part 2]	16 weeks	Progression/relapse free survival is the time from the start of study treatment to first documentation of disease progression or to death due to any cause, whichever occurrs first. Disease progression/relapse: Bone marrow blast ≥ 5%; or reappearance of blast in the blood; or development of extramedullary disease (EMD).

Secondary Outcome Measures

Name	Time	Method
Maximum Serum Concentration at Steady State (Cmax,ss) of PF-06747143 [Parts 1 and 2]	Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment	Assuming steady state was achieved, Cmax,ss was to be determined following multiple dosing to characterize the PK.
Volume of Distribution at Steady State (Vss) at of PF-06747143 [Parts 1 and 2]	Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment	Vss is the apparent volume of distribution at steady-state. If data permitted, Vss was to be determined following multiple dosing to characterize the PK.
Terminal Elimination Half-Life (t1/2) at Steady State of PF-06747143 [Parts 1 and 2]	Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment	t1/2 is the time measured for the serum concentration to decrease by one half.
Number of Participants With Chemistry Laboratory Abnormalities by Type and Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade [Part 1]	1 year	Chemistry laboratory abnormalities included alanine aminotransferase (ALT), alkaline phosphatase, aspartate aminotransferase (AST), bilirubin (total), creatinine, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, and hypophosphatemia. Each laboratory parameter was graded per NCI CTCAE version 4.03.
Incidence of Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (Nab) Against PF-06747143 [Part 2]	Days 1 and 15 pre-dose of Cycle 1, Day 1 pre-dose of Cycles 2-6, Day 1 pre-dose of every 3 cycles thereafter, and at end of treatment	Samples were to be analyzed for ADA using a validated assay. ADA positive samples were to be further analyzed for Nab using a validated assay.
Maximum Observed Serum Concentration (Cmax) of PF-06747143 [Parts 1 and 2]	Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment	Cmax of PF-06747143 was the peak serum concentration to be observed directly from data.
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-06747143 [Parts 1 and 2]	Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment	AUClast is area under the serum concentration versus time profile from time zero to the time of the last quantifiable concentration.
Duration of Objective Response Rate (ORR) [Part 1]	16 weeks	Duration of ORR is the time from first documentation of MLFS, CR, CRc, CRm, PR, CRi or PRi to date of first documentation of disease progression or death due to any cause. MLFS: BM blasts \<5%; absence of blasts with Auer rods and EMD. CR: MLFS criteria; ANC\>1000/ul and platelet \>100,000/ul; independence from red cell transfusions. CRc: Reversion to a normal karyotype at the time of CR in cases with an abnormal karyotype at the time of diagnosis; based on the evaluation of 20 metaphase cells from BM. CRm: Reversion to a molecular-negative phenotype at the time of CR. CRi: All CR criteria except for ANC \<1000/ul or platelet \<100,000/ul. PR: ANC \>1000/ul and platelet \>100,000/ul; BM blasts decreased to 5-25% and ≥50% decrease from pre-treatment levels. PRi: ANC \<1000/ul or platelet \<100,000/ul; BM blasts decreased to 5-25% and ≥50% decrease from pre-treatment levels. Disease progression/relapse: BM blast ≥5%; or reappearance of blast in the blood; or development of EMD.
Progression Free Survival [Part 1]	16 weeks	Progression/relapse free survival is the time from the start of study treatment to first documentation of disease progression or to death due to any cause, whichever occurrs first. Disease progression/relapse: Bone marrow blast ≥ 5%; or reappearance of blast in the blood; or development of extramedullary disease (EMD).
Incidence of Anti-Drug Antibodies (ADA) Against PF-06747143 [Part 1]	Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, end of treatment	Samples were tested for ADA using a validated assay. Number of participants with positive ADA samples was determined.
Minimum Observed Serum Trough Concentration at Steady State (Cmin,ss) of PF-06747143 [Parts 1 and 2]	Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment	Cmin is the minimum observed serum concentration. Assuming steady state was achieved, Cmin,ss was to be determined following multiple dosing to characterize the PK.
Area Under the Curve From Time Zero to End of Dosing Interval at Steady State (AUCtau,ss) of PF-06747143 [Parts 1 and 2]	Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment	AUCtau is area under the serum concentration versus time profile from time zero to the time tau (ie, dosing interval). Assuming steady state was achieved, AUCtau,ss was to be determined following multiple dosing to characterize the PK.
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [Part 1]	1 year	An AE was any untoward medical occurrence in a participant administered a product or medical device without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening experience (immediate risk of dying); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment. AEs included non-serious AEs and SAEs. Causality to study treatment was determined by the investigator.
Number of Participants With Treatment-Emergent Adverse Events (AEs) by Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade [Part 1]	1 year	An AE was any untoward medical occurrence in a participant administered a product or medical device without regard to possibility of causal relationship. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment. AEs were graded by the investigator according to NCI CTCAE version 4.03 (Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE). AEs included non-serious AEs and SAEs.
Objective Response Rate (ORR) - Percentage of Participants With Objective Response [Part 1]	16 weeks	Objective Response was defined as morphologic leukemia-free state (MLFS), complete remission (CR), cytogenetic CR (CRc), molecular CR (CRm), partial remission (PR), or CR or PR with incomplete blood count recovery (CRi or PRi). MLFS: Bone marrow (BM) blasts \<5%; absence of blasts with Auer rods and extramedullary disease (EMD). CR: MLFS criteria; absolute neutrophil count (ANC)\>1000/ul and platelet \>100,000/ul; independence from red cell transfusions. CRc: Reversion to a normal karyotype at the time of CR in cases with an abnormal karyotype at the time of diagnosis; based on the evaluation of 20 metaphase cells from BM. CRm: Reversion to a molecular-negative phenotype at the time of CR. CRi: All CR criteria except for ANC \<1000/ul or platelet \<100,000/ul. PR: ANC \>1000/ul and platelet \>100,000/ul; BM blasts decreased to 5-25% and ≥50% decrease from pre-treatment levels. PRi: ANC \<1000/ul or platelet \<100,000/ul; BM blasts decreased to 5-25% and ≥50% decrease from pre-treatment levels.
Number of Participants With Hematology Laboratory Abnormalities by Type and Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade [Part 1]	1 year	Hematology laboratory abnormalities included anemia, hemoglobin increased, lymphocyte count increased, lymphopenia, neutrophil count decreased, platelet count decreased, and white blood cell (WBC) decreased. Each laboratory parameter was graded per NCI CTCAE version 4.03.
Incidence of Neutralizing Antibodies (Nab) Against PF-06747143 [Part 1]	Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, end of treatment	Samples tested positive for ADA were to be further analyzed for Nab using a validated assay.
Time to Reach Maximum Observed Serum Concentration (Tmax) of PF-06747143 [Parts 1 and 2]	Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment	Tmax of PF-06747143 was to be observed directly from data as time of first occurrence of peak serum concentration.
Area Under the Curve From Time Zero to Infinity (AUCinf) of PF-06747143 [Parts 1 and 2]	Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment	AUCinf is area under the serum concentration versus time profile from time zero extrapolated to infinite time. If data permitted, AUCinf was to be estimated.
Apparent Volume of Distribution (Vd) of PF-06747143 [Parts 1 and 2]	Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment	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 blood concentration of a drug.
Terminal Elimination Half-Life (t1/2) of PF-06747143 [Parts 1 and 2]	Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment	t1/2 is the time measured for the serum concentration to decrease by one half. If data permitted, t1/2 was to be estimated.
Clearance (CL) of PF-06747143 [Parts 1 and 2]	Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment	CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Clearance (CL) at Steady State of PF-06747143 [Parts 1 and 2]	Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment	If data permitted, CL was to be determined following multiple dosing to characterize the PK.
Accumulation Ratio (Rac) of PF-06747143 [Parts 1 and 2]	Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment	Accumulation ratio (Rac) was to be obtained from AUCtau at steady state (AUCtau,ss) divided by AUCtau after single dose.
Peak and Trough PF-06747143 Concentrations for Selected Doses [Part 2]	Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment	Peak and trough PF-06747143 concentrations were to be observed directly from data.

Trial Locations

Locations (4): Wake Forest Baptist Health
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Winston-Salem, North Carolina, United States
The University of Arizona Cancer Center-North Campus
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Tucson, Arizona, United States
Banner-University Medical Center Tucson
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Tucson, Arizona, United States
The University of Chicago Medical Center
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Chicago, Illinois, United States