Study of Carfilzomib in Combination With Induction Chemotherapy in Children With Relapsed or Refractory Acute Lymphoblastic Leukemia

NCT02303821 | Completed Phase 1 Results DMC

• 2 other identifiers: CFZ0082014-001633-84
• Study Type: interventional
• Target: 141
• Locations: 32 countries
• Sites: 117

Brief Summary

The purpose of Phase 1b of this study is to:

• Asses the safety, tolerability and activity of carfilzomib, alone and in combination with induction chemotherapy, in children with relapsed or refractory acute lymphoblastic leukemia (ALL).
• Determine the maximum tolerated dose (MTD) and to recommend a phase 2 dose of carfilzomib in combination with induction chemotherapy. The purpose of Phase 2 of this study is to compare the rate of complete remission (CR) of carfilzomib in combination with vincristine, dexamethasone, PEG asparaginase, daunorubicin (VXLD) at the end of induction therapy to an appropriate external control.

Conditions

Acute Lymphoblastic Leukemia (ALL)

Outcome Measures

Primary Outcomes (3)

• Phase 1b: Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)

  An adverse event (AE) is any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment. TEAEs are AEs that occurred after the start of study treatment and up to the end of the study or 30 days of the last study treatment, whichever is earlier. Any clinically significant changes in vital signs, electrocardiograms, and clinical laboratory tests that occurred after study treatment administration were recorded as TEAEs. Treatment-related AEs (TRAEs) were TEAEs considered related to at least one study drug by the investigator, including those with unknown relationship. A serious AE (SAE) was defined as any untoward medical occurrence that resulted in death, was immediately life threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or another medically important serious event.

  From first dose up to 30 days after the last dose of study treatment; maximum duration of treatment was 8 weeks

• Phase 1b: Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)

  A DLT was defined as any of the following toxicities assessed by the investigator as possibly, probably, or definitely attributable to carfilzomib, with protocol defined exclusions: Any Grade 4 nonhematologic toxicity, ≥ Grade 4 neutropenia or ≥ Grade 3 thrombocytopenia.

  Up to approximately 35 days

• Phase 2: Percentage of Participants With Complete Remission (CR) After Induction Therapy

  CR was defined as: 1. Attainment of M1 bone marrow status (less than 5% blasts in a bone marrow aspirate and at least 200 cells counted) with no evidence of circulating blasts or extramedullary disease. 2. Recovery of peripheral counts: * Absolute neutrophil count (ANC) greater than or equal to 1000/µL * Platelet count greater than or equal to 100000/µL. * Assessed between days 29 and 45 Data was adjusted as inverse probability of treatment weight (IPTW) for the average treatment effect of the treated (IPTW-ATTW).

  Up to Day 50 (28-day cycle of induction therapy + recovery window from Day 29 to Day 45 [Day 36 to Day 50 for infants])

Secondary Outcomes (19)

• Phase 1b: Maximum Concentration (Cmax) of Carfilzomib Alone and in Combination

  Lead-in Cycle Day 1 (7-day cycle) and Induction Cycle Day 8 (28-day cycle): pre-dose, 15 minutes (m) after the start of infusion, immediately (within 2m) before the end of infusion (EOI), EOI, 10m, 30m, 1 hour (h), 2 h, and 4h post-dose

• Phase 1b: Area Under the Curve (AUC) From Time 0 to the Last Quantifiable Timepoint (AUClast) of Carfilzomib

  Lead-in Cycle Day 1 (7-day cycle) and Induction Cycle Day 8 (28-day cycle): pre-dose, 15m after the start of infusion, immediately (within 2m) before the EOI, EOI, 10m, 30m, 1h, 2 h, and 4h post-dose

• Phase 1b: AUC From Time 0 to Infinity (AUCinf) of Carfilzomib

  Lead-in Cycle Day 1 (7-day cycle) and Induction Cycle Day 8 (28-day cycle): pre-dose, 15m after the start of infusion, immediately (within 2m) before the EOI, EOI, 10m, 30m, 1h, 2 h, and 4h post-dose

• Phase 1b: Percentage of Participants Who Achieved a Combined CR and CR Without Platelet Recovery (CRp) at the End of Induction Cycle

  Up to approximately Day 29 of Induction Cycle (28-days cycle, assessment on Day 29)

• Phase 1b: Percentage of Participants Achieving Minimal Residual Disease (MRD) Status of <10-³ and <10-⁴ Lymphoblasts at the End of Induction Cycle

  Up to approximately Day 29 of Induction Cycle (28-days cycle, assessment on Day29)

Study Arms (4)

Phase 1b: Dose Escalation 1

EXPERIMENTAL

Subjects will receive carfilzomib in combination with induction chemotherapy, comprising an R3 backbone of dexamethasone, mitoxantrone, PEG asparaginase, and vincristine. Subjects will have a 1 week carfilzomib single agent Lead in Window prior to the Induction Cycle. Subjects will receive a 4 week cycle of induction chemotherapy and have the option to receive a 4 week cycle of consolidation chemotherapy (Children's Oncology Group (COG) modified Berlin Frankfurt Münster (BFM) chemotherapy backbone (6 mercaptopurine, cyclophosphamide, cytarabine, PEG asparaginase, vincristine), if stable disease or better response is achieved at the end of the Induction Cycle.

Drug: Carfilzomib; Drug: Dexamethasone; Drug: Mitoxantrone; Drug: PEG-asparaginase; Drug: Vincristine; Drug: Intrathecal (IT) Methotrexate; Drug: Intrathecal Triple Therapy (Intrathecal Cytarabine, Hydrocortisone, and Methotrexate); Drug: 6-Mercaptopurine; Drug: Cyclophosphamide; Drug: Cytarabine

Phase 1b: Dose Escalation 2

EXPERIMENTAL

Subjects will receive carfilzomib in combination with induction chemotherapy, comprising a VXLD backbone of vincristine, dexamethasone, PEG asparaginase, and daunorubicin. Subjects will receive a 4 week cycle of carfilzomib and induction chemotherapy and then have the option to receive a 4 week cycle of consolidation chemotherapy (Children's Oncology Group (COG) modified Berlin Frankfurt Münster (BFM) chemotherapy backbone (6 mercaptopurine, cyclophosphamide, cytarabine, PEG asparaginase, vincristine), if stable disease or better response is achieved at the end of the Induction Cycle.

Drug: Carfilzomib; Drug: Dexamethasone; Drug: PEG-asparaginase; Drug: Vincristine; Drug: Intrathecal (IT) Methotrexate; Drug: Intrathecal Triple Therapy (Intrathecal Cytarabine, Hydrocortisone, and Methotrexate); Drug: 6-Mercaptopurine; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin

Phase 2: Aged ≥ 12 months at screening

EXPERIMENTAL

All subjects aged ≥ 12 months at screening. Subjects will receive the recommended phase 2 dose (RP2D) of carfilzomib determined in Phase 1b. Subjects will receive a 4 week cycle of carfilzomib and induction chemotherapy comprising of a VXLD backbone of vincristine, dexamethasone, PEG asparaginase and daunorubicin. Subjects will then have the option to receive a 4 week cycle of carfilzomib in combination with consolidation chemotherapy Children's Oncology Group (COG) modified Berlin Frankfurt Münster (BFM) chemotherapy backbone (6 mercaptopurine, cyclophosphamide, cytarabine, PEG asparaginase, vincristine) if subjects showed no disease progression at the end of the Induction Cycle.

Drug: Carfilzomib; Drug: Dexamethasone; Drug: PEG-asparaginase; Drug: Vincristine; Drug: Intrathecal (IT) Methotrexate; Drug: Intrathecal Triple Therapy (Intrathecal Cytarabine, Hydrocortisone, and Methotrexate); Drug: 6-Mercaptopurine; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin

Phase 2: Aged < 12 months at screening

EXPERIMENTAL

All subjects aged \< 12 months at screening. Subjects will receive the recommended phase 2 dose (RP2D) of carfilzomib determined in Phase 1b. Subjects will receive a modified 5 week cycle (based on Interfant-06) of carfilzomib and induction chemotherapy comprising of a VXLD backbone of vincristine, dexamethasone, PEG asparaginase and daunorubicin. Subjects will then have the option to receive a 5 week cycle (modified based on Interfant-06) of carfilzomib in combination with consolidation chemotherapy Children's Oncology Group (COG) modified Berlin Frankfurt Münster (BFM) chemotherapy backbone (6 mercaptopurine, cyclophosphamide, cytarabine, PEG asparaginase, vincristine), if subjects showed no disease progression at the end of the Induction Cycle.

Drug: Carfilzomib; Drug: Dexamethasone; Drug: PEG-asparaginase; Drug: Vincristine; Drug: Intrathecal (IT) Methotrexate; Drug: Intrathecal Triple Therapy (Intrathecal Cytarabine, Hydrocortisone, and Methotrexate); Drug: 6-Mercaptopurine; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin

Interventions

Carfilzomib DRUG

Also known as: PR-171, PR171, Kyprolis® (carfilzomib) for Injection

Phase 1b: Dose Escalation 1; Phase 1b: Dose Escalation 2; Phase 2: Aged < 12 months at screening; Phase 2: Aged ≥ 12 months at screening

Dexamethasone DRUG

Phase 1b: Dose Escalation 1; Phase 1b: Dose Escalation 2; Phase 2: Aged < 12 months at screening; Phase 2: Aged ≥ 12 months at screening

Mitoxantrone DRUG

Phase 1b: Dose Escalation 1

PEG-asparaginase DRUG

Phase 1b: Dose Escalation 1; Phase 1b: Dose Escalation 2; Phase 2: Aged < 12 months at screening; Phase 2: Aged ≥ 12 months at screening

Vincristine DRUG

Phase 1b: Dose Escalation 1; Phase 1b: Dose Escalation 2; Phase 2: Aged < 12 months at screening; Phase 2: Aged ≥ 12 months at screening

Intrathecal (IT) Methotrexate DRUG

Phase 1b: Dose Escalation 1; Phase 1b: Dose Escalation 2; Phase 2: Aged < 12 months at screening; Phase 2: Aged ≥ 12 months at screening

Intrathecal Triple Therapy (Intrathecal Cytarabine, Hydrocortisone, and Methotrexate) DRUG

Phase 1b: Dose Escalation 1; Phase 1b: Dose Escalation 2; Phase 2: Aged < 12 months at screening; Phase 2: Aged ≥ 12 months at screening

6-Mercaptopurine DRUG

Phase 1b: Dose Escalation 1; Phase 1b: Dose Escalation 2; Phase 2: Aged < 12 months at screening; Phase 2: Aged ≥ 12 months at screening

Cyclophosphamide DRUG

Phase 1b: Dose Escalation 1; Phase 1b: Dose Escalation 2; Phase 2: Aged < 12 months at screening; Phase 2: Aged ≥ 12 months at screening

Cytarabine DRUG

Phase 1b: Dose Escalation 1; Phase 1b: Dose Escalation 2; Phase 2: Aged < 12 months at screening; Phase 2: Aged ≥ 12 months at screening

Daunorubicin DRUG

Phase 1b: Dose Escalation 2; Phase 2: Aged < 12 months at screening; Phase 2: Aged ≥ 12 months at screening

Eligibility Criteria

• Age: 1 Month - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age 21 years or younger at the time of initial ALL diagnosis and age \> 1 year at the time of study treatment initiation.
• Subjects must have a diagnosis of relapsed or refractory ALL with ≥ 5% blasts in the bone marrow (M2 or M3 disease), with or without extramedullary disease.
• To be eligible, subjects must have had 1 or more prior therapeutic attempts, defined as:
• Early first relapse (\< 36 months from original diagnosis) after achieving a CR (B-ALL) or first relapse any time following the original diagnosis after achieving a CR (T-ALL)
• First refractory bone marrow relapse occurring any time after original diagnosis after achieving a CR (ie, ≥1 failed attempt to induce a second remission) OR
• Relapse after achieving a CR following the first or subsequent relapse (i.e., ≥ 2 relapses) OR
• Failing to achieve a CR from original diagnosis after at least 1 induction attempt
• Subjects must have fully recovered from the acute toxic effects of all previous chemotherapy, immunotherapy, or radiotherapy treatment before enrollment.
• Subjects must have a serum creatinine level that is ≤ 1.5 × institutional upper limit of normal (ULN) according to age. If serum creatinine level is \> 1.5 × ULN, the subject must have a calculated creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70 mL/min/1.73 m2.
• Adequate liver function, defined as both of the following:
• Total bilirubin ≤ 1.5 × institutional ULN except in the presence of Gilbert Syndrome
• Alanine aminotransferase (ALT) ≤ 5 × institutional ULN
• Performance status: Karnofsky or Lansky scores ≥ 50 for subjects \> 16 years old or ≤ 16 years old, respectively.
• Subject's legally acceptable representative has provided informed consent when the subject is legally too young to provide informed consent and the subject has provided written assent based on local regulations and/or guidelines prior to any study-specific activities/procedures being initiated, except for standard of care local testing as permitted per protocol.
• Age greater than or equal to 1 month to less than 21 years. Subjects greater than or equal to 18 years must have had their original diagnosis at less than 18 years of age.

You may not qualify if:

• Known allergy to any of the drugs used in the study (Subjects who have had a previous allergy to PEG-asparaginase and if able, may receive Erwinia asparaginase at the investigator's discretion)
• Known allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib)
• Left ventricular fractional shortening \< 30%
• History of ≥ Grade 2 pancreatitis
• Active graft-versus-host disease requiring systemic treatment
• Positive culture for or other clinical evidence of infection with bacteria or fungus within 14 days of the initiation of study treatment
• Down Syndrome
• Prior therapy restrictions:
• Subjects must have completed therapy with granulocyte-colony stimulating factor (G-CSF) or other myeloid growth factors at least 7 days before study treatment initiation, or at least 14 days before study treatment initiation, if pegylated myeloid growth factors were administered.
• Subjects must have completed any type of active immunotherapy (e.g., tumor vaccines) at least 42 days before study treatment initiation.
• Subjects must have received the last dose of a non-monoclonal antibody biologic agent at least 7 days before study treatment initiation.
• At least 3 antibody half-lives must have elapsed since the last dose of monoclonal antibody (e.g., 66 days for rituximab and 69 days for epratuzumab) before subjects may initiate study treatment.
• Subjects must not have received other antineoplastic agents with therapeutic intent, excluding hydroxyurea and antimetabolites administered as part of maintenance chemotherapy, within 7 days prior to study treatment initiation.
• Hepatitis B infection with positive hepatitis B DNA
• Prior treatment with carfilzomib.

Sponsors & Collaborators

• Amgen: lead
• Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) - Study Design & Execution Collaborator: collaborator
• Innovative Therapies For Children with Cancer Consortium: collaborator

Study Sites (122)

University of California San Francisco Benioff Childrens Hospital Oakland

Oakland, California, 94609, United States

Location

Childrens Hospital of Orange County

Orange, California, 92868, United States

Location

Childrens Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Childrens Healthcare of Atlanta, Egleston

Atlanta, Georgia, 30322, United States

Location

Lurie Childrens Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

The Sidney Kimmel Comprehensive Cancer Center at John Hopkins

Baltimore, Maryland, 21231, United States

Location

Childrens Hospital and Clinics of Minnesota

Minneapolis, Minnesota, 55404, United States

Location

Childrens Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Childrens Hospital of New York Presbyterian

New York, New York, 10032, United States

Location

Levine Childrens Hospital at Carolinas Medical Center d/b/a Atrium Health

Charlotte, North Carolina, 28203, United States

Location

Cincinnati Childrens Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Nationwide Childrens Hospital

Columbus, Ohio, 43205, United States

Location

Childrens Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104-4318, United States

Location

Saint Judes Childrens Research Hospital

Memphis, Tennessee, 38105, United States

Location

Childrens Medical Center

Dallas, Texas, 75390, United States

Location

Texas Childrens Hospital West Tower

Houston, Texas, 77030, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229-4493, United States

Location

University of Utah Medical Center Primary Childrens Medical Center

Salt Lake City, Utah, 84113, United States

Location

West Virginia University Medicine Childrens

Morgantown, West Virginia, 60637, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Hospital Aleman

Ciudad Autonoma de Buenos Aires, Buenos Aires, C1118AAT, Argentina

Location

Hospital Italiano de Buenos Aires

Ciudad Autonoma de Buenos Aires, Buenos Aires, C1199, Argentina

Location

Hospital Universitario Austral

Pilar, Buenos Aires, B1629ODT, Argentina

Location

Sydney Childrens Hospital

Randwick, New South Wales, 2031, Australia

Location

The Childrens Hospital at Westmead

Westmead, New South Wales, 2145, Australia

Location

Queensland Childrens Hospital

South Brisbane, Queensland, 4101, Australia

Location

The Royal Childrens Hospital

Parkville, Victoria, 3052, Australia

Location

Perth Childrens Hospital

Nedlands, Western Australia, 6909, Australia

Location

St Anna Kinderspital

Vienna, 1090, Austria

Location

Hospital São Rafael - IDOR

Salvador, Estado de Bahia, 41253-190, Brazil

Location

Hospital da Crianca de Brasília

Brasília, Federal District, 70684-831, Brazil

Location

Liga Paranaense do Combate ao Cancer - Hospital Erasto Gaertner

Curitba, Paraná, 81520-060, Brazil

Location

Hospital Pequeno Principe

Curitiba, Paraná, 80250-060, Brazil

Location

Instituto de Medicina Integral Professor Fernando Figueira

Recife, Pernambuco, 50070-550, Brazil

Location

Hospital de Clinicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

Hospital da Crianca Santo Antonio Irmandade Santa Casa de Misericordia de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90050-170, Brazil

Location

Fundacao Pio 12 Hospital de Amor de Barretos

Barretos, São Paulo, 14784-400, Brazil

Location

Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo

Ribeirão Preto, São Paulo, 14040-900, Brazil

Location

Itaci Instituto de Tratamento do Cancer Infantil

São Paulo, São Paulo, 05403-000, Brazil

Location

Beneficencia Portuguesa de Sao Paulo

São Paulo, 01323-001, Brazil

Location

University Multiprofile Hospital for Active Treatment Tsaritsa Yoanna-ISUL EAD

Sofia, 1527, Bulgaria

Location

Centre Hospitalier Universitaire Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Hospital Luis Calvo Mackenna

Santiago, 7500539, Chile

Location

Hospital Roberto del Rio

Santiago, Chile

Location

Sociedad de Oncologia y Hematologia del Cesar

Valledupar, Cesar Department, 200001, Colombia

Location

Clinica Imbanaco S.A.S

Cali, Valle del Cauca Department, 760042, Colombia

Location

Fakultni nemocnice Brno

Brno, 613 00, Czechia

Location

University Hospital Rigshospitalet

København Ø, 2100, Denmark

Location

Centre Hospitalier Universitaire de Bordeaux - Hopital Pellegrin

Bordeaux, 33076, France

Location

Centre Hospitalier Regional Universitaire de Lille

Lille, 59037, France

Location

Hopital Armand Trousseau

Paris, 75012, France

Location

Hopital Robert Debre

Paris, 75019, France

Location

Centre Hospitalier Universitaire de Toulouse - Hopital des enfants

Toulouse, 31059, France

Location

Centre Hospitalier Universitaire de Nancy - Hopital Enfants de Brabois

Vandœuvre-lès-Nancy, 54511, France

Location

Agia Sofia Children Hospital

Athens, 11527, Greece

Location

Agia Sofia Children Hospital

Goudi, 11527, Greece

Location

General Children Hospital Panagioti and Aglaias Kyriakou

Goudi, 11527, Greece

Location

General University Hospital of Patras Panagia i Voithia

Pátrai, 26504, Greece

Location

Ippokrateio General Hospital of Thessaloniki

Thessaloniki, 54642, Greece

Location

Hong Kong Childrens Hospital

Kowloon Bay, Hong Kong

Location

Sheba Medical Center

Tel Litwinsky, 5262000, Israel

Location

Azienda Ospedaliera Universitaria Consorziale Policlinico di Bari

Bari, 70124, Italy

Location

Azienda Ospedaliera Universitaria Policlinico Vittorio Emanuele Presidio Ospedaliero G Rodolico

Catania, 95123, Italy

Location

IRCCS Istituto Giannina Gaslini

Genova, 16147, Italy

Location

Fondazione IRCCS San Gerardo dei Tintori

Monza (MB), 20900, Italy

Location

Azienda Ospedaliera di Rilievo Nazionale Santobono Pausilipon

Napoli, 80123, Italy

Location

Azienda Ospedaliera di Padova

Padua, 35128, Italy

Location

Fondazione IRCCS Policlinico San Matteo

Pavia, 27100, Italy

Location

IRCCS Ospedale Pediatrico Bambino Gesu

Roma, 00165, Italy

Location

Azienda Ospedaliera Citta della Salute e della Scienza Torino Ospedale Infantile Regina Margherita

Torino, 10126, Italy

Location

BRCR Global Mexico

Guadalajara, Jalisco, 44600, Mexico

Location

BRCR Global Mexico

Mexico City, Mexico City, 01120, Mexico

Location

Instituto Nacional de Pediatria

Mexico City, Mexico City, 04530, Mexico

Location

BRCR Global Mexico

Puebla City, 72160, Mexico

Location

Prinses Maxima Centrum voor Kinderoncologie

Utrecht, 3584 CS, Netherlands

Location

Oslo Universitetssykehus Rikshospitalet

Oslo, 0372, Norway

Location

Uniwersytecki Szpital Dzieciecy w Krakowie

Krakow, 30-663, Poland

Location

CSK Uniwersytetu Medycznego w Lodzi Uniwersyteckie Centrum Pediatrii im Marii Konopnickiej

Lodz, 91-738, Poland

Location

Uniwersytecki szpital dzieciecy

Lublin, 20-093, Poland

Location

Uck wum dzieciecy szpital kliniczny im jozefa polikarpa brudzinskiego

Warsaw, 02-091, Poland

Location

Uniwersytecki Szpital Kliniczny im Jana Mikulicza-Radeckiego we Wroclawiu

Wroclaw, 50-556, Poland

Location

SPSK nr 1 im Prof Stanislawa Szyszko Slaskiego Uniwersytetu Medycznego w Katowicach

Zabrze, 41-800, Poland

Location

Centro Hospitalar Universitario de Coimbra

Coimbra, 3000-602, Portugal

Location

Instituto Portugues de Oncologia de Lisboa Francisco Gentil, EPE

Lisbon, 1099-023, Portugal

Location

Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE

Porto, 4200-072, Portugal

Location

Institutul Clinic Fundeni

Bucharest, 022328, Romania

Location

Institutul Oncologic Prof Dr Ion Chiricuta Cluj-Napoca

Cluj-Napoca, 400015, Romania

Location

Spitalul Clinic de Urgenta pentru Copii Louis Turcanu Timisoara

Timișoara, 300011, Romania

Location

FSBI N N Blokhin Russian Oncology Research Center Ministry of Health of Russian Federation

Moscow, 115478, Russia

Location

FSBI FSCC of pediatric hematology, oncology and immunology n a Dmitry Rogachev

Moscow, 117198, Russia

Location

SBEI of HPE Saint Petersburg State Medical University na academic I P Pavlov of MoH of RF

Saint Petersburg, 197022, Russia

Location

King Fahad Medical City

Riyadh, 11525, Saudi Arabia

Location

National University Hospital

Singapore, 119228, Singapore

Location

KK Womens and Childrens Hospital

Singapore, 229899, Singapore

Location

Chris Hani Baragwanath Hospital

Johannesburg, 1864, South Africa

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Pusan National University Yangsan Hospital

Yangsan-si, Gyeongsangnam-do, 50612, South Korea

Location

Hospital Sant Joan de Deu

Esplugues de Llobregat, Catalonia, 08950, Spain

Location

Hospital Universitario Infantil Niño Jesus

Madrid, 28009, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Karolinska Universitetssjukhuset Solna

Solna, 171 76, Sweden

Location

National Taiwan University Hospital

Taipei, 10041, Taiwan

Location

Mackay Memorial Hospital Taipei Branch

Taipei, 10449, Taiwan

Location

Linkou Chang Gung Memorial Hospital

Taoyuan District, 33305, Taiwan

Location

King Chulalongkorn Memorial Hospital

Bangkok, 10330, Thailand

Location

Phramongkutklao Hospital

Bangkok, 10400, Thailand

Location

Ramathibodi Hospital

Bangkok, 10400, Thailand

Location

Siriraj Hospital

Bangkok, 10700, Thailand

Location

Acibadem Adana Hastanesi

Adana, 01130, Turkey (Türkiye)

Location

Ankara Universitesi Tip Fakultesi Hastanesi

Ankara, 06590, Turkey (Türkiye)

Location

Ankara Bilkent Sehir Hastanesi

Ankara, 06800, Turkey (Türkiye)

Location

Medical Park Antalya Hastanesi

Antalya, 07230, Turkey (Türkiye)

Location

Bursa Uludag Universitesi Tip Fakultesi

Bursa, 16059, Turkey (Türkiye)

Location

Medical Park Bahcelievler Hastanesi

Istanbul, 34160, Turkey (Türkiye)

Location

Medipol Mega Universite Hastanesi

Istanbul, 34214, Turkey (Türkiye)

Location

Ege Universitesi Tip Fakultesi

Izmir, 35040, Turkey (Türkiye)

Location

Erciyes Universitesi Tip Fakultesi Mustafa Eraslan ve Fevzi Mercan Cocuk Hastanesi

Kayseri, 38039, Turkey (Türkiye)

Location

The Royal Marsden NHS Foundation Trust

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (1)

• Burke MJ, Ziegler DS, Bautista F, Attarbaschi A, Gore L, Locatelli F, M O'Brien M, Pauly M, Kormany WN, Tian S, Morris CL, Baruchel A. Phase 1b study of carfilzomib with induction chemotherapy in pediatric relapsed/refractory acute lymphoblastic leukemia. Pediatr Blood Cancer. 2022 Dec;69(12):e29999. doi: 10.1002/pbc.29999. Epub 2022 Oct 10.

  PMID: 36215217 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

carfilzomib; WW Domain-Containing Oxidoreductase; Dexamethasone; Mitoxantrone; pegaspargase; Vincristine; Methotrexate; Hydrocortisone; Mercaptopurine; Cyclophosphamide; Cytarabine; Daunorubicin

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Short Chain Dehydrogenase-Reductases; NAD (+) and NADP (+) Dependent Alcohol Oxidoreductases; Alcohol Oxidoreductases; Oxidoreductases; Enzymes; Enzymes and Coenzymes; Tumor Suppressor Proteins; Neoplasm Proteins; Proteins; Amino Acids, Peptides, and Proteins; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Quinones; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Aminopterin; Pterins; Pteridines; Pregnenediones; Pregnenes; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids; Sulfhydryl Compounds; Sulfur Compounds; Purines; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthracyclines; Naphthacenes; Aminoglycosides; Glycosides; Carbohydrates

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2014
• First Posted: December 1, 2014
• Study Start: February 16, 2015
• Primary Completion: June 28, 2024
• Study Completion: June 28, 2024
• Last Updated: June 4, 2025
• Results First Posted: June 4, 2025

Record last verified: 2025-05

Locations

TU (9); GR (5); ZA (1); AU (1); RO (3); TW (3); FR (6); PT (3); US (22); CZ (1); TH (4); CA (1); SE (1); NO (1); RU (3); BR (11); SG (2); KR (4); DK (1); CL (2); CO (2); GB (1); SA (1); ES (3); ME (4); AR (3); HK (1); BU (1); IT (9); PL (6); NL (1); IL (1)