Clinical trial NCT02361346: Safety, PD & Efficacy of MT-3724 for the Treatment of Patients With Relapsed or Refractory DLBCL
Official title: Safety, Pharmacodynamics and Efficacy of MT-3724 for the Treatment of Patients With Relapsed or Refractory DLBCL
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Non-Hodgkin's B-cell Lymphoma
Leukemia, Lymphocytic, Chronic, B-Cell
Small Lymphocytic Leukemia
Diffuse Large B Cell Lymphoma
Blood Cancer
Hematological Malignancy
Keywords: CD20
immunotoxin
NHL
non-Hodgkin's lymphoma
lymphoma
cancer
antibodies
immunotherapy
safety
pharmacokinetics
maximum tolerated dose
MT-3724
relapsed
refractory
leukemia
CLL
SLL
DLBCL
efficacy
Lead sponsor: Molecular Templates, Inc.
Sponsor class: INDUSTRY
First posted: 2015-02-11
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and tolerability of MT-3724 in subjects with relapsed or refractory B-Cell NHL or relapsed and refractory CLL (Part 1 only) and relapsed and refractory DLBCL (Part 2 and Part 3). Part 3 evaluates the efficacy of MT-3724.

Detailed description: This is a three-part Phase 2 study

Part 1: (MT-3724 Dose Escalation) Define the maximum tolerated dose (MTD) of MT-3724 \[Completed\]

Part 2: (MTD Expansion Cohort) Confirm the safety and tolerability of the MTD of MT-3724 in the MTD Expansion Cohort.

Part 3: (Phase 2 MTD Expansion Cohort) Determine the efficacy of MT-3724 as monotherapy in subjects with relapsed or refractory DLBCL based on the overall response rate (ORR) by the revised Lugano Classification for Lymphoma adjusted according to LYRIC.

It is anticipated that up to 100 patients will be enrolled in Part 3. Treatment will continue for up to six 21 days cycles. If the subject exhibits SD, CR or PR after the end of Cycle 6 and the investigator determines that the benefit-risk ratio is favorable, then the treatment with MT-3724 may be continued after discussion with the sponsor.

Eligibility criteria: Inclusion Criteria:

* Participants must be informed about the study and fully consent to participation as demonstrated by signing the written ICF before any screening procedure.
* Male and female participants \>= 18 years of age at the time of informed consent.
* Participants must have relapsed or refractory Diffuse large B cell lymphoma (DLBCL) according to the Revised European American Lymphoma/World Health Organization classification. Participants must have proof of cluster of differentiation 20 plus (CD20+) DLBCL, based on either:

  * a. historical biopsies (obtained with diagnosis of relapsed or refractory disease), or
  * b. fresh biopsies
  * c. bone marrow biopsy, excisional lymph node biopsy, and core biopsy of any involved organ are all acceptable methods; Fine Needle Aspirate is not acceptable.
* Participants must have received at least 2 standard of care (SoC) regimens (including anti-CD20 antibody therapy) appropriate for DLBCL treatment.

  * a. Participants whose prior therapy includes chimeric antigen receptor T-cell (CAR-T-cell) therapy are eligible.
  * b. Participants who underwent stem cell transplant (SCT) \> 100 days for autologous SCT or \> 180 days for allogeneic SCT before study drug administration.
  * c. Participants who have been ineligible for SoC DLBCL treatments may be eligible at the investigator's discretion, upon sponsor approval.
* Participants must have at least 1 bi-dimensional tumor lesion at screening that is measurable by computerized tomography (CT) and/or magnetic resonance imaging (MRI) according to the Lugano criteria. Bi-dimensionally measurable tumor lesion by CT and/or MRI is defined as longest diameter of \> 1.5 centimeters (cm) for lymph nodes and \> 1.0 cm for extranodal disease.
* Participants must have life expectancy of \> 3 months from the start of treatment.
* Participants must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
* Participants must have met ALL the following laboratory criteria:

  * a. absolute neutrophil count (ANC) \>= 1.0 × 10\^9 cells per liter with no myeloid growth factors (granulocyte colony-stimulating factor \[G-CSF\] or granulocyte-macrophage colony-stimulating factor preparations) administered within 2 weeks of Cycle 1 Day 1.
  * b. platelet count \>= 50 × 10\^9 cells per liter with no Thrombopoietin-receptor agonists agents or platelet transfusions given within 2 weeks of Cycle 1 Day 1.
  * c. hemoglobin \>= 8.0 grams per deciliter (g/dL) with no erythropoietin stimulating agents or peripheral red blood cell (PRBC) transfusions within 2 weeks of Cycle 1 Day 1
  * d. creatinine clearance (CLcr) to be \>= 50 milliliter per minute (ml/min) either measured or estimated using the Cockcroft-Gault formula.
  * e. total bilirubin (or direct bilirubin for patients with Gilbert's disease \< 1.5 × upper limit of normal (ULN)
  * f. alanine transaminase (ALT) ≤ 3.0 × ULN (or \<= 5.0 x ULN if liver involvement).
  * g. aspartate aminotransferase (AST) \<= 3.0 × ULN (or \<= 5.0 x ULN if liver involvement).
  * h. international normalized ratio (INR) or prothrombin time (PT) \<= 1.5 x ULN (unless on therapeutic anticoagulants).
  * i. Activated partial thromboplastin time \<= 1.5 x ULN (unless on therapeutic anticoagulants).
* Have adequate serum albumin, as determined by: a. albumin \>= 3.0 g/dL.
* QT interval correction for heart rate using Fridericia's formula (QTcF) \<= 480 milliseconds determined as the average of 3 QTcF values from the triplicate electrocardiogram (ECG) obtained at screening.
* Women of reproductive potential must have a negative highly sensitive pregnancy test within 72 hours before the start of treatment. Women who are postmenopausal or permanently sterilized (eg, tubal occlusion, hysterectomy, bilateral salpingectomy) may be considered as not of reproductive potential.
* Participants of reproductive potential must agree either to abstain continuously from heterosexual intercourse or to use a highly effective birth control method from signing the informed consent until the short term follow-up (STFU) visit for females and until 90 days after the last dose of MT-3724 for males.
* Participants must be able to comply with all study-related procedures and medication use.

Exclusion Criteria

Prior or Current Therapies

* Received any amount of anti-CD20 monoclonal antibodies (mAbs) within the following periods before the start of treatment:

  * a. Rituximab (Rituxan®/MabThera® or rituximab biosimilar): within 84 days (12 weeks); if a participant has received rituximab within 37 weeks before the start of treatment, then serum rituximab level must be negative (\< 500 nanograms per milliliter \[ng/mL\]) at screening.
  * b. Obinutuzumab (Gazyva®/Gazyvaro®): 184 days c. Ofatumumab (Arzerra®): 88 days d. Any other anti-CD20 agents (eg, investigational agents), the washout period is 5 half-lives. The investigator must contact the medical monitor to discuss the most Compound: MT-3724 appropriate washout for non-approved CD20-targeting agents, where the half-life (t1/2) is not known.
* Received approved or investigational treatment for DLBCL within 4 weeks before the start of treatment. For small molecules (MW \< 0.9 kilodaltons \[kDa\]), the washout is 5 half-lives or at least 2 weeks. Radioimmunoconjugates are excluded within 12 weeks before the start of treatment.
* Received radiation therapy to tumor lesions that would serve as target lesions (measurable disease) within 4 weeks before the start of treatment, unless the lesion exhibited objective progression between radiation therapy and screening according to the Lugano Classification

  o a. Palliative radiation therapy to non-target lesions may be permitted at the investigator's discretion after consultation with the medical monitor and sponsor.
* Require the use of systemic immune modulators during study treatment:

  * a. Systemic immune modulators include, but are not limited to, systemic corticosteroids at doses \> 20 milligrams per day (mg/day) of prednisone equivalent, cyclosporine and tacrolimus.
  * b. The use of non-steroidal anti-inflammatory drugs (NSAIDS) is permitted.
* Received any live vaccines within 4 weeks before the start of treatment.
* Prior treatment with MT-3724.

Medical History

* Current evidence of Common Terminology Criteria for Adverse Events (CTCAE) Grade \> 1 toxicity (due to prior anticancer therapy) before the start of treatment, except for hair loss and those Grade 2 toxicities listed as permitted in other eligibility criteria.
* Current evidence of significant (CTCAE Grade ≥ 2) infection or wound within 4 weeks before the start of treatment. a. Participants with Grade 2 infection that has stabilized or improved with oral anti-infectives before the start of treatment may be eligible at the sponsor's discretion.
* Known or suspected hypersensitivity to the study drug or excipients contained in the study drug formulation.
* Current evidence of hypersensitivity or other underlying illness requiring systemic corticosteroids at doses \> 20 mg/day prednisone equivalent.
* Current evidence of uncontrolled human immunodeficiency syndrome (HIV), hepatitis B virus (HBV) or /hepatitis C virus (HCV) at screening. Serology testing is not required if seronegativity is documented in the medical history, and if there are no clinical signs suggestive of HIV or hepatitis infections, or suspected exposure. The following exceptions apply for participants with positive viral serology:

  * a. Participants with HIV and an undetectable viral load and CD4+ T-cell (CD4+) counts \>= 350 cells per milliliter may be enrolled, but must be taking appropriate opportunistic infection prophylaxis, if clinically relevant.
  * b. Participants with positive HBV serology are eligible if they have an undetectable viral load and the participant will receive antiviral prophylaxis for potential HBV reactivation per institutional guidelines.
  * c. Participants with positive HCV serology are eligible if quantitative polymerase chain reaction (PCR) for plasma HCV ribonucleic acid (RNA) is below the lower limit of detection. Concurrent antiviral HCV treatment per institutional guidelines is allowed.
* Current evidence of incomplete recovery from surgery or radiotherapy before start of treatment, or planned surgery or radiotherapy from the start of treatment until the end of treatment (EoT) visit, except minor elective surgery deemed acceptable by the investigator or palliative radiation therapy to non-target lesions.
* History of cardiovascular, renal, hepatic or any other disease within 3 months before the start of treatment that in the investigator's opinion, may increase the risks associated with study participation or require treatments that may interfere with the conduct of the study or the interpretation of study results.
* History or current evidence of neoplastic disease that is histologically distinct from NHL, except cervical carcinoma in situ, superficial noninvasive bladder tumors, curatively treated Stage I-II non-melanoma skin cancer. Participants with prior, curatively treated cancer \> 2 years ago before the start of treatment can be enrolled.
* Current evidence of new or growing brain or spinal metastases during screening. Participants with known brain or spinal metastases may be eligible if they:

  * a. Had radiotherapy or another appropriate therapy for the brain or spinal metastases; concurrent prophylactic treatment is allowed
  * b. Neurologic symptoms must be stable and no worse than Grade 2
  * c. Have evidence of stable brain or spinal disease on CT or MRI scan obtained within 4 weeks before signing the informed consent and compared with prior imaging results
  * d. Do not require steroid therapy (or, if applicable, have been stable on dose of no more than prednisone 20 mg/day or equivalent by C1D1)
* Women who are pregnant or breastfeeding.
* History of non-adherence to the schedule of procedures or medication use. 18. Current evidence of Graft vs Host Disease
* History or current evidence of significant cardiovascular disease including, but not limited to, the following conditions:

  * a. Unstable angina (symptoms of angina at rest) or new-onset angina within 3 months before the start of treatment.
  * b. Arterial thrombosis or pulmonary embolism within 3 months before the start of treatment.
  * c. Myocardial infarction or stroke within 3 months before the start of treatment.
  * d. Pericarditis (any CTCAE grade), pericardial effusion (CTCAE Grade \>= 2), non-malignant pleural effusion (CTCAE Grade ≥ 2) or malignant pleural effusion (CTCAE Grade \>= 3) within 3 months before the start of treatment with MT-3724.
  * e. Congestive heart failure (New York Heart Association \[NYHA\] Class III or IV) at screening or left ventricular ejection fraction (LVEF) \<= 45 percent (%), assessed by echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 1 month before starting study treatment (inclusion of participants with LVEF between 40% to 45% should be discussed with the medical monitor and approved by the sponsor). (ECHO or MUGA performed within 6 months before screening and at least 28 days after the last cancer therapy is acceptable provided the participant has not received any potentially cardiotoxic agents since then).
  * f. Cardiac arrhythmia requiring anti-arrhythmic therapy at screening. Participants receiving digoxin, calcium channel blockers, or beta-adrenergic blockers are eligible at the investigator's discretion after consultation with medical monitor and sponsor if the dose has been stable for \>= 2 weeks before the start of treatment with MT-3724. Participants with sinus arrhythmia and infrequent premature ventricular contractions are eligible at the investigator's discretion.

Primary outcomes:
measure: Part 1: Number of Participants With Dose Limiting Toxicities of a Single Cycle of MT-3724
timeFrame: Days 1, 3, 5, 8, 10 and 12
measure: Part 1 and 2: Maximum Observed Concentrations (Cmax) of MT-3274
timeFrame: Part 1 and 2 : Days 1, 3 and 12
measure: Part 1 and 2: Time to Achieve Cmax (Tmax) of MT-3724
timeFrame: Part 1 and 2: Days 1, 3 and 12
measure: Part 1 and 2: Area Under the Plasma Concentration Time Curve From 0 to 4 Hours (AUC [0-4]), AUC (0-infinity) and AUC From Dosing to Last Measurable Concentration (AUClast) of MT-3724
timeFrame: Part 1 and 2: Days 1, 3 and 12
measure: Part 1 and 2: Half Life (t1/2) of MT-3724
timeFrame: Part 1 and 2: Days 1, 3 and 12
measure: Part 1 and 2: Volume of Distribution (Vz) of MT-3724
timeFrame: Part 1 and 2: Days 1, 3 and 12
measure: Part 1 and 2: Clearance (CL) of MT-3724
timeFrame: Part 1 and 2: Days 1, 3 and 12
measure: Part 1 and 2: Absolute Values of Cluster of Differentiation 19 Plus (CD19+) for B-cell Lymphocytes
timeFrame: Part 1 and 2: Cycle 1: Days 8 and 23; Cycle 3: Day1; Cycle 5: Day 1 and Day 120 (end of study)
measure: Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed
timeFrame: Part 1 and 2: Cycle 1, Day 23; Cycle 2, Day 1; Cycle 3, Day 1; Cycle 4, Day 1; Cycle 5, Day 1 and Day 120 (end of study)
measure: Part 3: Number of Participants Reporting Serious Treatment-emergent Adverse Events (TEAEs) and Non-serious TEAEs
timeFrame: Up to Day 45
measure: Part 3: Number of Participants With Clinically Significant Laboratory Parameters
timeFrame: Up to Day 45
measure: Part 3: Number of Participants With Clinically Significant Electrocardiogram (ECG) Values
timeFrame: Up to Day 26
measure: Part 3: Number Participants With Clinically Significant Vital Signs
timeFrame: Up to Day 45
measure: Part 3: Number of Participants With Clinically Significant Physical Findings
timeFrame: Up to Day 26
measure: Part 4: Overall Response Rate (ORR) in MT-3724 Treated Participants With Relapsed or Refractory DLBCL
timeFrame: Up to Day 45
Secondary outcomes:
measure: Part 1 and 2: Number of Participants Reporting Worst Case Serious Treatment Emergent Adverse Events (TEAEs) and Non-serious TEAEs
timeFrame: Up to Day 45
measure: Part 3: ORR in MT-3724 Treated Participants With Relapsed or Refractory DLBCL by the Lugano Classification for Lymphoma
timeFrame: Up to Day 45
measure: Part 3: ORR in MT-3724 Treated Participants With Relapsed or Refractory DLBCL
timeFrame: Up to Day 45
measure: Part 3: Duration of Tumor Response (DOR) in MT-3724 Treated Participants With Relapsed or Refractory DLBCL
timeFrame: Up to Day 45
measure: Part 3: Disease Control Rate (DCR) in MT-3724 Treated Participants With Relapsed or Refractory DLBCL
timeFrame: Up to Day 45
measure: Part 3: Cmax of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL
timeFrame: Up to Day 45
measure: Part 3: Tmax of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL
timeFrame: Up to Day 45
measure: Part 3: AUC (0-4), AUC (0-infinity) and AUClast of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL
timeFrame: Up to Day 45
measure: Part 3: t1/2 of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL
timeFrame: Up to Day 45
measure: Part 3: Vz of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL
timeFrame: Up to Day 45
measure: Part 3: CL of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL
timeFrame: Up to Day 45
measure: Part 3: PD of MT-3724 Measured by B-cell Count in Participants With Relapsed or Refractory DCBCL
timeFrame: Up to Day 45
measure: Part 3: PD of MT-3724 Measured by Immunophenotyping in Participants With Relapsed or Refractory DCBCL
timeFrame: Up to Day 45
measure: Part 3: PD of MT-3724 Measured by Circulating Immunoglobulins in Participants With Relapsed or Refractory DCBCL
timeFrame: Up to Day 45
measure: Part 3: Number of Participants With ADA When Treated With MT-3724
timeFrame: Up to Day 45
measure: Part 4: DOR in MT-3724 Treated Participants With Relapsed or Refractory DLBCL
timeFrame: Up to Day 45
measure: Part 4: Number of Participants Reporting Serious Treatment-emergent Adverse Events (TEAEs) and Non-serious TEAEs
timeFrame: Up to Day 45
measure: Part 4: Number of Participants With SAEs
timeFrame: Up to Day 45
measure: Part 4: Number of Participants With Clinically Significant Laboratory Parameters
timeFrame: Up to Day 45
measure: Part 4: Number Participants With Clinically Significant Vital Signs
timeFrame: Up to Day 45
measure: Part 4: Number of Participants With Clinically Significant ECG Values
timeFrame: Up to Day 26
measure: Part 4: Number of Participants With Adverse Events Suggestive of Cardiotoxicity
timeFrame: Up to Day 26
measure: Part 4: ORR in MT-3724 Treated Participants With Relapsed or Refractory DLBCL
timeFrame: Up to Day 45
measure: Part 4: DCR in MT-3724 Treated Participants With Relapsed or Refractory DLBCL
timeFrame: Up to Day 45
measure: Part 4: Progression-free Survival (PFS) in MT-3724 Treated Participants With Relapsed or Refractory DLBCL
timeFrame: Up to Day 45
measure: Part 4: Overall Survival (OS) in MT-3724 Treated Participants With Relapsed or Refractory DLBCL
timeFrame: Up to Day 45
measure: Part 4: Cmax of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL
timeFrame: Up to Day 45
measure: Part 4: Tmax of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL
timeFrame: Up to Day 45
measure: Part 4: AUC (0-4), AUC (0-infinity) and AUClast of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL
timeFrame: Up to Day 45
measure: Part 4: t1/2 of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL
timeFrame: Up to Day 45
measure: Part 4: Vz of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL
timeFrame: Up to Day 45
measure: Part 4: CL of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL
timeFrame: Up to Day 45
measure: Part 4: PD of MT-3724 Measured by B-cell Count in Participants With Relapsed or Refractory DCBCL
timeFrame: Up to Day 45
measure: Part 4: PD of MT-3724 Measured by Immunophenotyping in Participants With Relapsed or Refractory DCBCL
timeFrame: Up to Day 45
measure: Part 4: PD of MT-3724 Measured by Circulating Immunoglobulins in Participants With Relapsed or Refractory DCBCL
timeFrame: Up to Day 45
measure: Part 4: Number of Participants With ADA When Treated With MT-3724
timeFrame: Up to Day 45
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Whittier
country: United States
facility: Innovative Clinical Research Institute, LLC
state: California
city: Jacksonville
country: United States
facility: 21st Century Oncology - Jacksonville
state: Florida
city: Orlando
country: United States
facility: Orlando Health, Inc.
state: Florida
city: Orlando
country: United States
facility: Orlando Health, Inc.
state: Florida
city: Plantation
country: United States
facility: BRCR Medical Center
state: Florida
city: Weeki Wachee
country: United States
facility: ASCLEPES Research Centers
state: Florida
city: Columbus
country: United States
facility: Columbus Regional Research Institute
state: Georgia
city: Chicago
country: United States
facility: University of Illinois, Cancer Center
state: Illinois
city: Tinley Park
country: United States
facility: Healthcare Research Network III, LLC
state: Illinois
city: Urbana
country: United States
facility: Carle Foundation Hospital
state: Illinois
city: Louisville
country: United States
facility: Norton Healthcare, Inc
state: Kentucky
city: New York
country: United States
facility: New York University Langone Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: UT Health San Antonio Cancer
state: Texas
city: Grodno
country: Belarus
facility: Grodno University Hospital
city: Minsk
country: Belarus
facility: Minsk City Clinical Oncology Center
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Kingston
country: Canada
facility: Cancer Centre of Southeastern Ontario at Kingston General Hospital
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Quebec
country: Canada
facility: Montreal Oncology Research
city: Tbilisi
country: Georgia
facility: LLC ARENSIA Exploratory Medicine
city: Petah-Tikva
country: Israel
facility: Rabin Medical Center, Davidoff Cancer Center, Hemato-Oncology Institute
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center, Department of Hematology
city: Tel-Aviv
country: Israel
facility: The Tel Aviv Sourasky Medical Center, Department of Hematology and Bone Marrow Transplantation
city: Chisinau
country: Moldova, Republic of
facility: ARENSIA Exploratory Medicine,
city: Gliwice
country: Poland
facility: Maria Sklodowska-Curie National Institute of Oncology - National Research Institute
city: Kraków
country: Poland
facility: University Hospital in Krakow, Teaching Unit of the Hematology Department
city: Rzeszów
country: Poland
facility: Frederic Chopin Provincial Teaching Hospital, Teaching Department of Hematology
city: Torun
country: Poland
facility: Our Doctor Clinical Trials Center
city: Warsaw
country: Poland
facility: Institute of Hematology and Transfusion Medicine, Department of Hematology
city: Wroclaw
country: Poland
facility: Jan Mikulicz Radecki University Hospital in Wroclaw, Department and Clinic of Hematology, Blood Neoplasms and Bone Marrow Transplantation
city: Kragujevac
country: Serbia
facility: Clinical Center Kragujevac, Clinic of Hematology
city: Novi Sad
country: Serbia
facility: Clinical Center of Vojvodina, Clinic of Hematology
city: Barcelona
country: Spain
facility: Catalan Institute of Oncology (ICO) - Hospital Duran i Reynals, Department of Clinical Hematology
city: Barcelona
country: Spain
facility: University Hospital Vall d'Hebron (HUVH), Department of Hematology
city: Madrid
country: Spain
facility: Hospital Universitario QuironSalud Madrid
city: Seville
country: Spain
facility: University Hospital Virgen del Rocio (HUVR), Department of Hematology
city: Kyiv
country: Ukraine
facility: Medical Center of Limited Liability Company "Medical Centre Named by Academician Yurii Spizhenko
Study officials:
References: