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

Acute Lymphoblastic Leukemia (ALL) Clinical Trial

Official title:

Phase 1b/2 Study of Carfilzomib in Combination With Induction Chemotherapy in Children With Relapsed or Refractory Acute Lymphoblastic Leukemia

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02303821
• Other study ID #: CFZ008
• Secondary ID: 2014-001633-84
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: February 16, 2015
• Est. completion date: July 14, 2024

Study information

• Verified date: April 2024
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 130
• Est. completion date: July 14, 2024
• Est. primary completion date: July 14, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 21 Years

Eligibility

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).

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia (ALL)
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• Carfilzomib

• Dexamethasone

• Mitoxantrone

• PEG-asparaginase

• Vincristine

• Intrathecal (IT) Methotrexate

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

• 6-Mercaptopurine

• Cyclophosphamide

• Cytarabine

• Daunorubicin

Locations

Country	Name	City	State
Argentina	Hospital Aleman	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	Hospital Italiano de Buenos Aires	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	Hospital Universitario Austral	Pilar	Buenos Aires
Australia	Perth Childrens Hospital	Nedlands	Western Australia
Australia	The Royal Childrens Hospital	Parkville	Victoria
Australia	Sydney Childrens Hospital	Randwick	New South Wales
Australia	Queensland Childrens Hospital	South Brisbane	Queensland
Australia	The Childrens Hospital at Westmead	Westmead	New South Wales
Austria	St Anna Kinderspital	Wien
Brazil	Fundacao Pio 12 Hospital de Amor de Barretos	Barretos	São Paulo
Brazil	Hospital da Crianca de Brasília	Brasília	Distrito Federal
Brazil	Liga Paranaense do Combate ao Cancer - Hospital Erasto Gaertner	Curitba	Paraná
Brazil	Hospital Pequeno Principe	Curitiba	Paraná
Brazil	Hospital da Crianca Santo Antonio Irmandade Santa Casa de Misericordia de Porto Alegre	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital de Clinicas de Porto Alegre	Porto Alegre	Rio Grande Do Sul
Brazil	Instituto de Medicina Integral Professor Fernando Figueira	Recife	Pernambuco
Brazil	Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo	Ribeirao Preto	São Paulo
Brazil	Hospital São Rafael - IDOR	Salvador	Bahia
Brazil	Itaci Instituto de Tratamento do Cancer Infantil	Sao Paulo	São Paulo
Brazil	Beneficencia Portuguesa de Sao Paulo	São Paulo
Bulgaria	University Multiprofile Hospital for Active Treatment Tsaritsa Yoanna-ISUL EAD	Sofia
Canada	Centre Hospitalier Universitaire Sainte-Justine	Montreal	Quebec
Chile	Hospital Roberto del Rio	Santiago
Chile	Hospital Luis Calvo Mackenna	Santiago de Chile
Colombia	Clinica Imbanaco S.A.S	Cali	Valle Del Cauca
Colombia	Sociedad de Oncologia y Hematologia del Cesar	Valledupar	Cesar
Czechia	Fakultni nemocnice Brno	Brno
Denmark	University Hospital Rigshospitalet	Kobenhavn O
France	Centre Hospitalier Universitaire de Bordeaux - Hopital Pellegrin	Bordeaux Cedex
France	Centre Hospitalier Regional Universitaire de Lille	Lille
France	Hopital Armand Trousseau	Paris
France	Hopital Robert Debre	Paris
France	Centre Hospitalier Universitaire de Toulouse - Hopital des enfants	Toulouse Cedex 9
France	Centre Hospitalier Universitaire de Nancy - Hopital Enfants de Brabois	Vandoeuvre les Nancy Cedex
Greece	Agia Sofia Children Hospital	Athens
Greece	Agia Sofia Children Hospital	Goudi
Greece	General Children Hospital Panagioti and Aglaias Kyriakou	Goudi
Greece	General University Hospital of Patras Panagia i Voithia	Patra
Greece	Ippokrateio General Hospital of Thessaloniki	Thessaloniki
Hong Kong	Hong Kong Childrens Hospital	Kowloon Bay
Israel	Sheba Medical Center	Tel Hashomer
Italy	Azienda Ospedaliera Universitaria Consorziale Policlinico di Bari	Bari
Italy	Azienda Ospedaliera Universitaria Policlinico Vittorio Emanuele Presidio Ospedaliero G Rodolico	Catania
Italy	IRCCS Istituto Giannina Gaslini	Genova
Italy	Fondazione IRCCS San Gerardo dei Tintori	Monza (MB)
Italy	Azienda Ospedaliera di Rilievo Nazionale Santobono Pausilipon	Napoli
Italy	Azienda Ospedaliera di Padova	Padova
Italy	Fondazione IRCCS Policlinico San Matteo	Pavia
Italy	IRCCS Ospedale Pediatrico Bambino Gesu	Roma
Italy	Azienda Ospedaliera Citta della Salute e della Scienza Torino Ospedale Infantile Regina Margherita	Torino
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Pusan National University Yangsan Hospital	Yangsan-si, Gyeongsangnam-do
Mexico	BRCR Global Mexico	Guadalajara	Jalisco
Mexico	BRCR Global Mexico	Mexico	Distrito Federal
Mexico	Instituto Nacional de Pediatria	Mexico	Distrito Federal
Mexico	BRCR Global Mexico	Puebla
Netherlands	Prinses Maxima Centrum voor Kinderoncologie	Utrecht
Norway	Oslo Universitetssykehus Rikshospitalet	Oslo
Poland	Uniwersytecki Szpital Dzieciecy w Krakowie	Krakow
Poland	CSK Uniwersytetu Medycznego w Lodzi Uniwersyteckie Centrum Pediatrii im Marii Konopnickiej	Lodz
Poland	Uniwersytecki szpital dzieciecy	Lublin
Poland	Uck wum dzieciecy szpital kliniczny im jozefa polikarpa brudzinskiego	Warszawa
Poland	Uniwersytecki Szpital Kliniczny im Jana Mikulicza-Radeckiego we Wroclawiu	Wroclaw
Poland	SPSK nr 1 im Prof Stanislawa Szyszko Slaskiego Uniwersytetu Medycznego w Katowicach	Zabrze
Portugal	Centro Hospitalar Universitario de Coimbra	Coimbra
Portugal	Instituto Portugues de Oncologia de Lisboa Francisco Gentil, EPE	Lisboa
Portugal	Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE	Porto
Romania	Institutul Clinic Fundeni	Bucharest
Romania	Institutul Oncologic Prof Dr Ion Chiricuta Cluj-Napoca	Cluj Napoca
Romania	Spitalul Clinic de Urgenta pentru Copii Louis Turcanu Timisoara	Timisoara
Russian Federation	FSBI FSCC of pediatric hematology, oncology and immunology n a Dmitry Rogachev	Moscow
Russian Federation	FSBI N N Blokhin Russian Oncology Research Center Ministry of Health of Russian Federation	Moscow
Russian Federation	SBEI of HPE Saint Petersburg State Medical University na academic I P Pavlov of MoH of RF	Saint Petersburg
Saudi Arabia	King Fahad Medical City	Riyadh
Singapore	KK Womens and Childrens Hospital	Singapore
Singapore	National University Hospital	Singapore
South Africa	Chris Hani Baragwanath Hospital	Johannesburg
Spain	Hospital Sant Joan de Deu	Esplugues de Llobregat	Cataluña
Spain	Hospital Universitario Infantil Niño Jesus	Madrid
Spain	Hospital Universitario La Paz	Madrid
Sweden	Karolinska Universitetssjukhuset Solna	Solna
Taiwan	Mackay Memorial Hospital Taipei Branch	Taipei
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Linkou Chang Gung Memorial Hospital	Taoyuan
Thailand	King Chulalongkorn Memorial Hospital	Bangkok
Thailand	Phramongkutklao Hospital	Bangkok
Thailand	Ramathibodi Hospital	Bangkok
Thailand	Siriraj Hospital	Bangkok
Turkey	Acibadem Adana Hastanesi	Adana
Turkey	Ankara Bilkent Sehir Hastanesi	Ankara
Turkey	Ankara Universitesi Tip Fakultesi Hastanesi	Ankara
Turkey	Medical Park Antalya Hastanesi	Antalya
Turkey	Bursa Uludag Universitesi Tip Fakultesi	Bursa
Turkey	Medical Park Bahcelievler Hastanesi	Istanbul
Turkey	Medipol Mega Universite Hastanesi	Istanbul
Turkey	Ege Universitesi Tip Fakultesi	Izmir
Turkey	Erciyes Universitesi Tip Fakultesi Mustafa Eraslan ve Fevzi Mercan Cocuk Hastanesi	Kayseri
United Kingdom	The Royal Marsden NHS Foundation Trust	Sutton
United States	Childrens Healthcare of Atlanta, Egleston	Atlanta	Georgia
United States	Childrens Hospital Colorado	Aurora	Colorado
United States	The Sidney Kimmel Comprehensive Cancer Center at John Hopkins	Baltimore	Maryland
United States	Levine Childrens Hospital at Carolinas Medical Center d/b/a Atrium Health	Charlotte	North Carolina
United States	Lurie Childrens Hospital of Chicago	Chicago	Illinois
United States	Cincinnati Childrens Hospital Medical Center	Cincinnati	Ohio
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	Nationwide Childrens Hospital	Columbus	Ohio
United States	Childrens Medical Center	Dallas	Texas
United States	Texas Childrens Hospital West Tower	Houston	Texas
United States	Childrens Mercy Hospital	Kansas City	Missouri
United States	Saint Judes Childrens Research Hospital	Memphis	Tennessee
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Childrens Hospital and Clinics of Minnesota	Minneapolis	Minnesota
United States	West Virginia University Medicine Childrens	Morgantown	West Virginia
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Childrens Hospital of New York Presbyterian	New York	New York
United States	University of California San Francisco Benioff Childrens Hospital Oakland	Oakland	California
United States	Childrens Hospital of Orange County	Orange	California
United States	Childrens Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	University of Utah Medical Center Primary Childrens Medical Center	Salt Lake City	Utah
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas

Sponsors (3)

Lead Sponsor	Collaborator
Amgen	Innovative Therapies For Children with Cancer Consortium, Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) - Study Design & Execution Collaborator

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Brazil,  Bulgaria,  Canada,  Chile,  Colombia,  Czechia,  Denmark,  France,  Greece,  Hong Kong,  Israel,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  Norway,  Poland,  Portugal,  Romania,  Russian Federation,  Saudi Arabia,  Singapore,  South Africa,  Spain,  Sweden,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1b: Number of Subjects who Experience One or More Adverse Events (AE)		36 months
Primary	Phase 1b: Number of Subjects who Experience One or More Serious Adverse Events (SAEs)		36 months
Primary	Phase 1b: Number of Subjects who Experienced a Clinically Significant Change from Baseline in Key Laboratory Analytes	Changes from baseline in key laboratory analytes.	36 months
Primary	Phase 1b: Number of Subjects who Experience a Clinically Significant Change from Baseline in Vital Signs	Changes from baseline in vital signs	36 months
Primary	Phase 1b: Number of Subjects who Experience a Clinically Significant Change from Baseline in Physical Findings	Changes from baseline in physical findings	36 months
Primary	Phase 1b: Time to Toxicity	Time to toxicity will be evaluated to differentiate single-agent carfilzomib from carfilzomib in combination with induction chemotherapy	36 months
Primary	Phase 1b: Maximum Tolerated Dose (MTD)	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%.	36 months
Primary	Complete Remission (CR) after induction therapy	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.	Within 14 days of Induction and/or Consolidation cycle completion
Primary	Complete Remission (CR) Rate After Induction Therapy in Subjects Aged Less Than 12 Months at Screening	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.	From Day 36 up to a maximum of Day 50
Secondary	Phase 1b: Maximum plasma concentration (Cmax)	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).	36 months
Secondary	Phase 1b: Total Plasma Exposure - Area Under the Curve (AUC)	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).	36 months
Secondary	Phase 1b: Number of Subjects who Experience Complete Remission (CR) or Complete Remission with Incomplete Hematological Recovery (CRi)		36 months
Secondary	Phase 1b: Minimal Residual Disease (MRD) Status	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)	36 months
Secondary	Phase 2: Number of Subjects who Experience a Treatment-emergent Adverse Event (TEAE)		29 months
Secondary	Phase 2: Number of Subjects who Experience a Treatment-related Adverse Event		29 months
Secondary	Phase 2: Number of Subjects who Experience a Severe Adverse Event		29 months
Secondary	Phase 2: Number of Subjects who Experience a Laboratory Abnormality		29 months
Secondary	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)		29 months
Secondary	Phase 2: Event Free Survival (EFS)	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.	29 months
Secondary	Phase 2: Overall Survival (OS)	OS defined as time from initiation of therapy until death from any cause.	29 months
Secondary	Phase 2: Duration of Response (DOR)	DOR, defined as time from earliest of CR, CRp, CRh, or CRi to relapse or death from any cause.	29 months
Secondary	Phase 2: Minimal Residual Disease (MRD) Status in Subjects Achieving CR	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)	29 months
Secondary	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)	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).	29 months
Secondary	Number of Subjects who Experience a Stem Cell Transplant or Chimeric Antigen Receptor T Cell Therapy (CAR-T)		29 months
Secondary	Phase 2: Number of Subjects who Experience a Clinically Significant Change from Baseline in Laboratory Analytes		29 months
Secondary	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		Day 29 and 45
Secondary	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		Day 36 to 50
Secondary	Phase 2: Maximum Plasma Concentration (Cmax)		29 months
Secondary	Phase 2: Area Under the Concentration-time Curve (AUC)		29 months
Secondary	Phase 2: Half-life (t1/2) of Carfilzomib		29 months

External Links

•   AmgenTrials clinical trials website