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

• ClinicalTrials.gov Identifier: NCT02303821
• Recruitment Status: Recruiting
• First Posted: December 1, 2014
• Last Update Posted: March 9, 2023
• Sponsor: Amgen
• Collaborators: Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) - Study Design & Execution Collaborator; Innovative Therapies For Children with Cancer Consortium
• Information provided by (Responsible Party): Amgen

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Acute Lymphoblastic Leukemia (ALL)	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; Drug: Daunorubicin	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 118 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 1b/2 Study of Carfilzomib in Combination With Induction Chemotherapy in Children With Relapsed or Refractory Acute Lymphoblastic Leukemia
• Actual Study Start Date: February 16, 2015
• Estimated Primary Completion Date: February 22, 2024
• Estimated Study Completion Date: February 22, 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: Phase 1b: Dose Escalation 1; 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; Other Names: PR-171; PR171; Kyprolis® (carfilzomib) for Injection; 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
Experimental: Phase 1b: Dose Escalation 2; 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; Other Names: PR-171; PR171; Kyprolis® (carfilzomib) for Injection; 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
Experimental: Phase 2: Aged ≥ 12 months at screening; 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; Other Names: PR-171; PR171; Kyprolis® (carfilzomib) for Injection; 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
Experimental: Phase 2: Aged < 12 months at screening; 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; Other Names: PR-171; PR171; Kyprolis® (carfilzomib) for Injection; 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

Outcome Measures

Primary Outcome Measures :

1. Phase 1b: Number of Subjects who Experience One or More Adverse Events (AE) [ Time Frame: 36 months ]
2. Phase 1b: Number of Subjects who Experience One or More Serious Adverse Events (SAEs) [ Time Frame: 36 months ]
3. Phase 1b: Number of Subjects who Experienced a Clinically Significant Change from Baseline in Key Laboratory Analytes [ Time Frame: 36 months ]
   Changes from baseline in key laboratory analytes.
4. Phase 1b: Number of Subjects who Experience a Clinically Significant Change from Baseline in Vital Signs [ Time Frame: 36 months ]
   Changes from baseline in vital signs
5. Phase 1b: Number of Subjects who Experience a Clinically Significant Change from Baseline in Physical Findings [ Time Frame: 36 months ]
   Changes from baseline in physical findings
6. Phase 1b: Time to Toxicity [ Time Frame: 36 months ]
   Time to toxicity will be evaluated to differentiate single-agent carfilzomib from carfilzomib in combination with induction chemotherapy
7. Phase 1b: Maximum Tolerated Dose (MTD) [ Time Frame: 36 months ]
   Maximum tolerated dose (MTD) of carfilzomib in combination with induction chemotherapy. Determination of the MTD as the dose that has the highest posterior probability of having a dose-limiting toxicity (DLT) rate within the target toxicity interval (20%-33%), while the posterior probability of excessive/unacceptable toxicity (>33%-100%) is less than 40%.
8. Complete Remission (CR) after induction therapy [ Time Frame: Within 14 days of Induction and/or Consolidation cycle completion ]
   CR will be assessed in all subjects who do not show disease progression during induction therapy (Day 1 to Day 28) within 14 days, or start of alternative therapy, whichever comes first. Subjects can receive alternative therapy after completing induction therapy on Day 28.
9. Complete Remission (CR) Rate After Induction Therapy in Subjects Aged Less Than 12 Months at Screening [ Time Frame: From Day 36 up to a maximum of Day 50 ]
   CR will be assessed in all subjects who do not show disease progression during induction therapy (Modified based on Interfant-06: Day 1 to Day 35) between Day 36 and Day 50, or start of alternative therapy, whichever comes first. Subjects can receive alternative therapy after completing induction therapy on Day 35.

Secondary Outcome Measures :

1. Phase 1b: Maximum plasma concentration (Cmax) [ Time Frame: 36 months ]
   Maximum plasma concentration (Cmax), alone and in combination with induction chemotherapy, will be derived from levels of carfilzomib assayed in Pharmacokinetic (PK) samples. Estimates for Cmax will be tabulated and summarized (i.e., mean, standard deviation).
2. Phase 1b: Total Plasma Exposure - Area Under the Curve (AUC) [ Time Frame: 36 months ]
   Total Plasma Exposure - Area Under the Curve (AUC), alone and in combination with induction chemotherapy, will be derived from levels of carfilzomib assayed in Pharmacokinetic (PK) samples. Estimates for AUC will be tabulated and summarized (i.e., mean, standard deviation).
3. Phase 1b: Number of Subjects who Experience Complete Remission (CR) or Complete Remission with Incomplete Hematological Recovery (CRi) [ Time Frame: 36 months ]
4. Phase 1b: Minimal Residual Disease (MRD) Status [ Time Frame: 36 months ]
   Proportion of subjects who achieve MRD status < 10-3 and < 10-4 lymphoblasts at the end of the Induction Cycle as assessed by quantitative immunoglobulin/T-cell receptor (Ig/TcR) polymerase chain reaction (PCR)
5. Phase 2: Number of Subjects who Experience a Treatment-emergent Adverse Event (TEAE) [ Time Frame: 29 months ]
6. Phase 2: Number of Subjects who Experience a Treatment-related Adverse Event [ Time Frame: 29 months ]
7. Phase 2: Number of Subjects who Experience a Severe Adverse Event [ Time Frame: 29 months ]
8. Phase 2: Number of Subjects who Experience a Laboratory Abnormality [ Time Frame: 29 months ]
9. Phase 2: Number of Subjects who Experience Complete Remission (CR), Complete Remission with Incomplete Recovery of Platelets (CRp), CR with Partial Hematological Recovery (CRh) or Complete Remission with Incomplete Hematological Recovery (CRi) [ Time Frame: 29 months ]
10. Phase 2: Event Free Survival (EFS) [ Time Frame: 29 months ]
    EFS, defined as time from initiation of therapy until treatment failure (defined as failure to reach at least a CRi after consolidation or after induction in subjects that do not receive consolidation), relapse, or death from any cause.
11. Phase 2: Overall Survival (OS) [ Time Frame: 29 months ]
    OS defined as time from initiation of therapy until death from any cause.
12. Phase 2: Duration of Response (DOR) [ Time Frame: 29 months ]
    DOR, defined as time from earliest of CR, CRp, CRh, or CRi to relapse or death from any cause.
13. Phase 2: Minimal Residual Disease (MRD) Status in Subjects Achieving CR [ Time Frame: 29 months ]
    Proportion of subjects who achieve MRD status less than 10^-4 lymphoblasts at the end of the Induction Cycle as assessed by quantitative immunoglobulin/T-cell receptor (Ig/TcR) polymerase chain reaction (PCR)
14. Minimal Residual Disease (MRD) Status in Subjects with Complete Remission (CR), CR with Incomplete Recovery of Platelets (CRp), CR with Partial Hematological Recovery (CRh) or CR with Incomplete Hematological Recovery (CRi) [ Time Frame: 29 months ]
    Proportion of subjects who achieve MRD status less than 10^-3 and less than 10^-4 lymphoblasts at the end of the Induction Cycle as assessed by quantitative immunoglobulin/T-cell receptor (Ig/TcR) polymerase chain reaction (PCR).
15. Number of Subjects who Experience a Stem Cell Transplant or Chimeric Antigen Receptor T Cell Therapy (CAR-T) [ Time Frame: 29 months ]
16. Phase 2: Number of Subjects who Experience a Clinically Significant Change from Baseline in Laboratory Analytes [ Time Frame: 29 months ]
17. Number of Subjects who Experience Complete Remission (CR), CR with Incomplete Recovery of Platelets (CRp), or CR with Incomplete Hematological Recovery (CRi) After Consolidation Therapy in Subjects Aged Greater Than or Equal to 12 Months at Screening [ Time Frame: Day 29 and 45 ]
18. Number of Subjects who Experience Complete Remission (CR), CR with Incomplete Recovery of Platelets (CRp), or CR with Incomplete Hematological Recovery (CRi) After Consolidation Therapy in Subjects Aged Less than 12 Months at Screening [ Time Frame: Day 36 to 50 ]
19. Phase 2: Maximum Plasma Concentration (Cmax) [ Time Frame: 29 months ]
20. Phase 2: Area Under the Concentration-time Curve (AUC) [ Time Frame: 29 months ]
21. Phase 2: Half-life (t1/2) of Carfilzomib [ Time Frame: 29 months ]

Eligibility Criteria

• Ages Eligible for Study: 1 Month to 21 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Phase 1b Key Inclusion Criteria:

1. Age 21 years or younger at the time of initial ALL diagnosis and age > 1 year at the time of study treatment initiation.

2. 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
3. Subjects must have fully recovered from the acute toxic effects of all previous chemotherapy, immunotherapy, or radiotherapy treatment before enrollment.
4. 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.

5. 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
6. Performance status: Karnofsky or Lansky scores ≥ 50 for subjects > 16 years old or ≤ 16 years old, respectively.

Phase 2 Inclusion Criteria:

1. 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.
2. 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.
3. Subjects must be diagnosed with relapsed or refractory relapsed ALL.
4. Subjects must have a documented first remission, less than 5% blasts in the bone marrow (M1 bone marrow) and no evidence of extramedullary disease.

5. T-cell ALL with bone marrow relapse (defined as greater than or equal to 5% leukemia blasts in bone marrow) or refractory relapse with or without extramedullary disease.

   OR B-cell ALL bone marrow relapse or refractory relapse (defined as greater than or equal to 5% leukemia blasts in bone marrow) after having received a targeted B-cell immune therapy (eg, blinatumomab, inotuzumab or a CAR-T therapy) with or without extramedullary disease..

6. Adequate liver function: bilirubin less than or equal to 1.5 x upper limit of normal (ULN), alanine aminotransferase (ALT) less than or equal to 5 x ULN.
7. Adequate renal function: serum creatinine less than or equal to 1.5 x ULN or glomerular filtration rate (GFR) greater than or equal to 70 mL/min/1.73 m^2; or for children less than 2 years of age, greater than or equal to 50 mL/min/1.73 m^2.
8. Adequate cardiac function: shortening fraction greater than or equal to 30% or ejection fraction greater than or equal to 50%.
9. Karnofsky (subjects greater than or equal to 16 years of age) or Lansky (subjects 12 months to less than 16 years of age) performance status greater than or equal to 50%.
10. Subjects must have fully recovered from the acute toxic effects of all previous chemotherapy, immunotherapy, or radiotherapy treatment before enrollment (for example: recovery from gastrointestinal toxicity may occur more rapidly than less reversible organ toxicities such as sinusoidal obstruction syndrome or non-infectious pneumonitis, for serious prior toxicities recommended discussion with Amgen medical monitor).
11. Life expectancy of greater than 6 weeks per investigator's judgement at time of screening.

Phase 1b Key Exclusion Criteria:

1. 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)
2. Known allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib)
3. Left ventricular fractional shortening < 30%
4. History of ≥ Grade 2 pancreatitis
5. Active graft-versus-host disease requiring systemic treatment
6. Positive culture for or other clinical evidence of infection with bacteria or fungus within 14 days of the initiation of study treatment
7. Down Syndrome

8. 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.
9. Hepatitis B infection with positive hepatitis B DNA

Phase 2 Exclusion Criteria:

1. Prior treatment with carfilzomib.
2. Intolerance, hypersensitivity, or inability to receive any of the chemotherapy components of the VXLD regimen. An exception is allowed for allergy to asparaginase products if Erwinia asparaginase is unable to be administered,
3. Autologous HSCT within 6 weeks prior to start of study treatment.
4. Allogeneic HSCT within 3 months prior to start of study treatment.
5. Active GVHD requiring systemic immune suppression.
6. Less than 30 days from discontinuation of immune suppressive therapy administered for the treatment of acute or chronic GVHD.
7. Isolated extramedullary relapse.
8. Positive bacterial or fungal infection within 14 days of enrollment (except for documented line infection, line has been removed, and blood culture after line removal is negative for 5 days prior to first dose of induction therapy). Antibiotics may be administered for prophylaxis as per institutional standards up to and after enrollment.
9. Subjects with less than 3 antibody half-lives since the last dose of monoclonal antibody (eg, 66 days for rituximab, 69 days for epratuzumab, inotuzumab for 36 days), prior to first dose of investigational product must be discussed with the Amgen medical monitor and may be allowed to enroll based on extent of disease or evidence of rapidly rising peripheral or bone marrow blast counts.
10. Cell-based immunotherapy (eg, donor leucocyte infusion, CAR-T cells, tumor vaccines) within 42 days prior to first dose of investigational product. If the Amgen medical monitor agrees, an exception may be granted to the 42-day requirement for subjects with rapidly rising peripheral or bone marrow blast counts.
11. Down's syndrome.
12. Presence of another active cancer.
13. History of grade greater than or equal to 2 pancreatitis within 6 months to screening.
14. Unresolved toxicities from prior anticancer therapy, defined as not having resolved to CTCAE version 4.03 grade 1 or to levels dictated in the eligibility criteria apart from alopecia or toxicities from prior anticancer therapy that are considered irreversible and do not trigger another exclusion criterion (defined as having been present and stable for greater than 4 weeks).
15. Antitumor therapy (chemotherapy, investigational agents, molecular-targeted therapy) within 7 days of day 1 of induction. Exception: hydroxyurea to control peripheral blood leukemic cell counts is allowed until start of investigational product.
16. Active viral infection, including but not limited to cytomegalovirus (CMV), Hepatitis B infection with positive serum hepatitis surface antigen or hepatitis B DNA, HIV, Hepatitis C with detectable hepatitis C RNA. Subjects who have previously received a stem cell transplant must be screened for CMV infection, unless both subject and donor are known to be CMV negative.
17. Currently receiving treatment in another investigational device or product study, or less than 14 days since ending treatment on another investigational device or product study.
18. Uncontrolled arrhythmias or screening ECG with corrected QT interval (QTc) of greater than 470 msec.
19. History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
20. Female subject is pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 6 months after the last dose of any study treatment or for 12 months after last dose of cyclophosphamide if administered during optional consolidation cycle.
21. Female subjects of childbearing potential unwilling to use 1 highly effective method of contraception during treatment and for an additional 6 months after the last dose of any study treatment or for 12 months after last dose of cyclophosphamide if administered during optional consolidation cycle.
22. Female subjects of childbearing potential with a positive pregnancy test assessed at Screening by a serum or urine pregnancy test.
23. Male subjects with a female partner of childbearing potential who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use a condom with spermicide during treatment and for an additional 6 months after the last dose of any study treatment, even if they have undergone a successful vasectomy.
24. Male subjects with a pregnant partner who are unwilling to practice abstinence or use a condom with spermicide during treatment, for duration of pregnancy, and for an additional 6 months after the last dose of any study treatment.
25. Male subjects unwilling to abstain from donating semen or sperm during treatment and for an additional 6 months after the last dose of any study treatment.
26. Known allergy to captisol (a cyclodextrin derivative used to solubilize carfilzomib; for a complete listing of Captisol-enabled drugs, see the Ligand Pharmaceuticals, Inc. website).

Contacts and Locations

Contacts

Contact: Amgen Call Center; 866-572-6436; medinfo@amgen.com

Locations

United States, California

UCSF Benioff Childrens Hospital Oakland; Recruiting

Oakland, California, United States, 94609

Childrens Hospital of Orange County; Recruiting

Orange, California, United States, 92868

United States, Colorado

Childrens Hospital Colorado; Recruiting

Aurora, Colorado, United States, 80045

United States, Georgia

Childrens Healthcare of Atlanta, Egleston; Recruiting

Atlanta, Georgia, United States, 30322

United States, Missouri

Childrens Mercy Hospital; Recruiting

Kansas City, Missouri, United States, 64108

United States, New Jersey

Rutgers Cancer Institute of New Jersey; Recruiting

New Brunswick, New Jersey, United States, 08903

United States, New York

Childrens Hospital of New York Presbyterian; Recruiting

New York, New York, United States, 10032

United States, North Carolina

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

Charlotte, North Carolina, United States, 28203

United States, Ohio

Cincinnati Childrens Hospital Medical Center; Recruiting

Cincinnati, Ohio, United States, 45229

United States, Pennsylvania

Childrens Hospital of Philadelphia; Recruiting

Philadelphia, Pennsylvania, United States, 19104-4318

United States, Texas

Childrens Medical Center; Recruiting

Dallas, Texas, United States, 75390

University of Texas Health Science Center at San Antonio; Recruiting

San Antonio, Texas, United States, 78229-4493

United States, West Virginia

West Virginia University Medicine Childrens; Recruiting

Morgantown, West Virginia, United States, 60637

United States, Wisconsin

Medical College of Wisconsin; Recruiting

Milwaukee, Wisconsin, United States, 53226

Argentina

Hospital Aleman; Recruiting

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

Hospital Italiano de Buenos Aires; Recruiting

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1199ABB

Hospital Universitario Austral; Recruiting

Pilar, Buenos Aires, Argentina, B1629ODT

Australia, New South Wales

Sydney Childrens Hospital; Recruiting

Randwick, New South Wales, Australia, 2031

The Childrens Hospital at Westmead; Recruiting

Westmead, New South Wales, Australia, 2145

Australia, Queensland

Queensland Childrens Hospital; Recruiting

South Brisbane, Queensland, Australia, 4101

Australia, Victoria

The Royal Childrens Hospital; Recruiting

Parkville, Victoria, Australia, 3052

Australia, Western Australia

Perth Childrens Hospital; Recruiting

Nedlands, Western Australia, Australia, 6909

Austria

St Anna Kinderspital; Recruiting

Wien, Austria, 1090

Brazil

São Rafael Hospital - IDOR; Recruiting

Salvador, Bahia, Brazil, 41253-190

Hospital da Crianca de Brasilia; Recruiting

Brasilia, Distrito Federal, Brazil, 70684-831

Hospital Pequeno Principe; Recruiting

Curitiba, Paraná, Brazil, 80250-060

Liga Paranaense do Combate ao Cancer - Hospital Erasto Gaertner; Recruiting

Curitiba, Paraná, Brazil, 81520-060

Instituto de Medicina Integral Professor Fernando Figueira IMIP; Recruiting

Recife, Pernambuco, Brazil, 50070-550

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

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

Fundacao Pio 12 Hospital de Amor de Barretos; Recruiting

Barretos, São Paulo, Brazil, 14784-400

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

Ribeirao Preto, São Paulo, Brazil, 14040-900

Itaci Instituto de Tratamento do Cancer Infantil; Recruiting

Sao Paulo, São Paulo, Brazil, 05403-000

Hospital de Clinicas de Porto Alegre; Recruiting

Porto Alegre, Brazil, 90035-903

Real e Benemérita Associação Portuguesa de Beneficência (Beneficência Portuguesa); Recruiting

São Paulo, Brazil, 01323-001

Bulgaria

University Multiprofile Hospital for Active Treatment Tsaritsa Yoanna-ISUL EAD; Recruiting

Sofia, Bulgaria, 1527

Canada, Quebec

Centre Hospitalier Universitaire Sainte-Justine; Recruiting

Montreal, Quebec, Canada, H3T 1C5

Chile

Hospital Luis Calvo Mackenna; Recruiting

Santiago de Chile, Chile, 7500539

Hospital Roberto del Rio; Recruiting

Santiago, Chile

Colombia

Sociedad de Oncologia y Hematologia del Cesar; Recruiting

Valledupar, Cesar, Colombia, 200001

Centro Medico Imbanaco de Cali S.A; Recruiting

Cali, Valle Del Cauca, Colombia, 760042

Czechia

Fakultni nemocnice Brno; Recruiting

Brno, Czechia, 613 00

Denmark

University Hospital Rigshospitalet; Recruiting

Kobenhavn O, Denmark, 2100

France

Centre Hospitalier Universitaire de Bordeaux - Hopital Pellegrin; Completed

Bordeaux Cedex, France, 33076

Centre Hospitalier Regional Universitaire de Lille; Completed

Lille, France, 59037

Hopital Armand Trousseau; Completed

Paris, France, 75012

Hopital Robert Debre; Recruiting

Paris, France, 75019

Centre Hospitalier Universitaire de Toulouse - Hopital des enfants; Completed

Toulouse Cedex 9, France, 31059

Centre Hospitalier Universitaire de Nancy - Hopital Enfants de Brabois; Completed

Vandoeuvre les Nancy Cedex, France, 54511

Greece

Agia Sofia Children Hospital; Recruiting

Athens, Greece, 11527

Agia Sofia Children Hospital; Recruiting

Goudi, Greece, 11527

General Children Hospital Panagioti and Aglaias Kyriakou; Recruiting

Goudi, Greece, 11527

General University Hospital of Patras Panagia i Voithia; Recruiting

Patra, Greece, 26504

Ippokrateio General Hospital of Thessaloniki; Recruiting

Thessaloniki, Greece, 54642

Hong Kong

Hong Kong Childrens Hospital; Recruiting

Hong Kong, Hong Kong

Israel

Sheba Medical Center; Completed

Tel Hashomer, Israel, 5262000

Italy

Azienda Ospedaliera Universitaria Consorziale Policlinico di Bari; Recruiting

Bari, Italy, 70124

Azienda Ospedaliera Universitaria Policlinico Vittorio Emanuele Presidio Ospedaliero G Rodolico; Recruiting

Catania, Italy, 95123

IRCCS Istituto Giannina Gaslini; Recruiting

Genova, Italy, 16147

Fondazione Monza e Brianza per il Bambino e la sua Mamma; Recruiting

Monza (MB), Italy, 20900

Azienda Ospedaliera di Rilievo Nazionale Santobono Pausilipon; Recruiting

Napoli, Italy, 80123

Azienda Ospedaliera di Padova; Recruiting

Padova, Italy, 35128

Fondazione IRCCS Policlinico San Matteo; Recruiting

Pavia, Italy, 27100

IRCCS Ospedale Pediatrico Bambino; Recruiting

Roma, Italy, 00165

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

Torino, Italy, 10126

Korea, Republic of

Seoul National University Hospital; Recruiting

Seoul, Korea, Republic of, 03080

Asan Medical Center; Recruiting

Seoul, Korea, Republic of, 05505

Samsung Medical Center; Recruiting

Seoul, Korea, Republic of, 06351

Pusan National University Yangsan Hospital; Recruiting

Yangsan-si, Gyeongsangnam-do, Korea, Republic of, 50612

Mexico

Instituto Nacional de Pediatria; Recruiting

Mexico City, Distrito Federal, Mexico, 4530

BRCR Global Mexico; Recruiting

Guadalajara, Jalisco, Mexico, 44600

Netherlands

Prinses Maxima Centrum voor Kinderoncologie; Recruiting

Utrecht, Netherlands, 3584 CS

Norway

Oslo Universitetssykehus Rikshospitalet; Recruiting

Oslo, Norway, 424

Poland

Uniwersytecki Szpital Dzieciecy w Krakowie; Recruiting

Krakow, Poland, 30-663

CSK Uniwersytetu Medycznego w Lodzi Uniwersyteckie Centrum Pediatrii im Marii Konopnickiej; Recruiting

Lodz, Poland, 91-738

Uniwersytecki szpital dzieciecy; Recruiting

Lublin, Poland, 20-093

UCK WUM Dzieciecy Szpital Kliniczny im Jozefa Polikarpa Brudzinskiego; Recruiting

Warszawa, Poland, 02-091

Uniwersytecki Szpital Kliniczny im Jana Mikulicza-Radeckiego we Wroclawiu; Recruiting

Wroclaw, Poland, 50-556

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

Zabrze, Poland, 41-800

Portugal

Centro Hospitalar Universitario de Coimbra; Recruiting

Coimbra, Portugal, 3000-602

Instituto Portugues de Oncologia de Lisboa Francisco Gentil, EPE; Recruiting

Lisboa, Portugal, 1099-023

Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE; Recruiting

Porto, Portugal, 4200-072

Romania

Institutul Clinic Fundeni; Recruiting

Bucharest, Romania, 022328

Institutul Oncologic Prof Dr Ion Chiricuta Cluj-Napoca; Recruiting

Cluj Napoca, Romania, 400015

Spitalul Clinic de Urgenta pentru Copii Louis Turcanu Timisoara; Recruiting

Timisoara, Romania, 300011

Russian Federation

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

Moscow, Russian Federation, 115478

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

Moscow, Russian Federation, 117198

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

Saint Petersburg, Russian Federation, 197022

Saudi Arabia

King Fahad Medical City; Recruiting

Riyadh, Saudi Arabia, 11525

Singapore

National University Hospital; Recruiting

Singapore, Singapore, 119228

KK Womens and Childrens Hospital; Recruiting

Singapore, Singapore, 229899

South Africa

Chris Hani Baragwanath Hospital; Recruiting

Johannesburg, South Africa, 1864

Spain

Hospital Sant Joan de Deu; Recruiting

Barcelona, Cataluña, Spain, 08950

Hospital Universitario Infantil Niño Jesus; Recruiting

Madrid, Spain, 28009

Hospital Universitario La Paz; Recruiting

Madrid, Spain, 28046

Sweden

Karolinska Universitetssjukhuset Solna; Recruiting

Solna, Sweden, 171 76

Taiwan

National Taiwan University Hospital; Recruiting

Taipei, Taiwan, 10041

Mackay Memorial Hospital Taipei Branch; Recruiting

Taipei, Taiwan, 10449

Linkou Chang Gung Memorial Hospital; Recruiting

Taoyuan, Taiwan, 33305

Thailand

Siriraj Hospital; Recruiting

Bangkok, Thailand, 10700

Turkey

Acibadem Adana Hastanesi; Recruiting

Adana, Turkey, 01130

Ankara Sehir Hastanesi; Recruiting

Ankara, Turkey, 06800

Ankara Universitesi Tip Fakultesi Hastanesi; Recruiting

Ankara, Turkey, 6590

Medical Park Antalya Hastanesi; Recruiting

Antalya, Turkey, 07230

Bursa Uludag Universitesi Tip Fakultesi; Recruiting

Bursa, Turkey, 16059

Medicalpark Bahcelievler Hastanesi; Recruiting

Istanbul, Turkey, 34160

Medipol Mega Universite Hastanesi; Recruiting

Istanbul, Turkey, 34214

Ege Universitesi Tip Fakultesi; Recruiting

Izmir, Turkey, 35100

Erciyes Universitesi Tip Fakultesi Mustafa Eraslan ve Fevzi Mercan Cocuk Hastanesi; Recruiting

Kayseri, Turkey, 38039

United Kingdom

The Royal Marsden NHS Foundation Trust; Terminated

Sutton, United Kingdom, SM2 5PT

Sponsors and Collaborators

Amgen

Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) - Study Design & Execution Collaborator

Innovative Therapies For Children with Cancer Consortium

Investigators

• Study Director: MD; Amgen

More Information

Additional Information:

AmgenTrials clinical trials website 

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT02303821
• Other Study ID Numbers: CFZ008; 2014-001633-84 ( EudraCT Number )
• First Posted: December 1, 2014
• Last Update Posted: March 9, 2023
• Last Verified: February 2023

Additional relevant MeSH terms:

Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Cytarabine; Dexamethasone; Hydrocortisone; Cyclophosphamide; Methotrexate; Vincristine; Daunorubicin; Asparaginase; Mitoxantrone; Mercaptopurine; Pegaspargase; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloablative Agonists; Anti-Inflammatory Agents