- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica NCT01363297
Study Evaluating Inotuzumab Ozogamicin In Acute Lymphocytic Leukemia
2 marzo 2017 aggiornato da: Pfizer
An Open-label, Phase 1/2 Study Of Inotuzumab Ozogamicin In Subjects With Relapsed Or Refractory Cd22-positive Acute Lymphocytic Leukemia
The Phase 1 portion of this study will assess the safety, tolerability and efficacy at increasing dose levels of inotuzumab ozogamicin in subjects with CD22-positive relapsed or refractory adult acute lymphocytic leukemia (ALL) in order to select the recommended phase 2 dose (RP2D) and schedule.
The Phase 2 portion of the study will evaluate the efficacy of inotuzumab ozogamicin as measured by hematologic remission rate (CR + CRi) in patients in second or later salvage status.
Panoramica dello studio
Stato
Completato
Condizioni
Intervento / Trattamento
Tipo di studio
Interventistico
Iscrizione (Effettivo)
72
Fase
- Fase 2
Contatti e Sedi
Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.
Luoghi di studio
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California
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Duarte, California, Stati Uniti, 91010-3000
- City of Hope National Medical Center
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Palo Alto, California, Stati Uniti, 94304
- Stanford Unversity Cancer Clinical Trials Office
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Palo Alto, California, Stati Uniti, 94304
- Stanford Unversity Hospital and Clinics, CTRU
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Stanford, California, Stati Uniti, 94305
- Stanford Cancer Institute
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Stanford, California, Stati Uniti, 94305
- Stanford University Hospital and Clinics
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Illinois
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Chicago, Illinois, Stati Uniti, 60637
- The University of Chicago Medical Center
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Massachusetts
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Boston, Massachusetts, Stati Uniti, 02215
- Beth Israel Deaconess Medical Center
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Boston, Massachusetts, Stati Uniti, 02215
- Dana-Farber Cancer Institute
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Boston, Massachusetts, Stati Uniti, 02114
- Massachusetts General Hospital (MGH)
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Boston, Massachusetts, Stati Uniti, 02115
- Brigham and Women's Hospital (BWH)
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Michigan
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Detroit, Michigan, Stati Uniti, 48201
- Karmanos Cancer Institute
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Farmington Hills, Michigan, Stati Uniti, 48334
- Karmanos Cancer Institute at Farmington Hills
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Ohio
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Cleveland, Ohio, Stati Uniti, 44195
- Cleveland Clinic
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Texas
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Houston, Texas, Stati Uniti, 77030
- The University of Texas MD Anderson Cancer Center
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Washington
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Seattle, Washington, Stati Uniti, 98109
- Seattle Cancer Care Alliance
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Criteri di partecipazione
I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.
Criteri di ammissibilità
Età idonea allo studio
18 anni e precedenti (Adulto, Adulto più anziano)
Accetta volontari sani
No
Sessi ammissibili allo studio
Tutto
Descrizione
Inclusion Criteria:
- Subjects with CD22-positive ALL with either refractory disease (i.e. disease progression or no response while receiving their most recent prior anti-cancer therapy), or relapsed disease (i.e. response to their most recent prior anti-cancer therapy with subsequent relapse). Subjects enrolled in the Phase 2 portion of the study must be due to receive salvage 2 or later therapy.
- Subjects with Philadelphia chromosome-positive (Ph+) ALL must have failed standard treatment with at least one tyrosine kinase inhibitor.
- Adequate renal and hepatic function, and negative pregnancy test for women of childbearing potential.
Exclusion Criteria:
- Subjects with isolated extramedullary relapse or active central nervous system (CNS) leukemia.
- Prior allogeneic hematopoietic stem cell transplant (HSCT) or other anti-CD22 immunotherapy within 4 months, or active graft versus host disease (GvHD) at study entry.
- Evidence or history of veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS).
Piano di studio
Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
---|---|
Sperimentale: Inotuzumab Ozogamicin
|
Part 1: Administered intravenously as 2 - 3 weekly doses over a 28-day cycle for a maximum of 6 cycles. Total dose per cycle 0.8 mg/m^2 to 2.0 mg/m^2. Part 2 Expansion and Part 3 Phase 2: Administered intravenously as 3 weekly doses over a 28-day cycle for a maximum of 6 cycles. Total initial dose per cycle 1.8 mg/m^2.
Altri nomi:
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
---|---|---|
Percentage of Participants Reporting Dose Limiting Toxicities (DLTs) During the Phase 1 Dose-Finding Phase
Lasso di tempo: Cycle 1
|
DLT was any of the following in the first cycle & attributable to inotuzumab ozogamicin: any greater than or equal to (≥) Grade 4 non-hematologic toxicity except nausea/vomiting (if manageable with supportive care), alopecia, & toxicities secondary to neutropenia & sepsis; prolonged myelosuppression (absolute neutrophil count [ANC] less than [<] 500 per microliter [/µL] or platelet count <25,000/µL in bone marrow with <5 percent (%) blasts & no evidence of leukemia more than 45 days beyond the most recent dose of test article); any Grade 3 non-hematologic toxicity (excluding toxicities such as alopecia or those secondary to neutropenia & sepsis) not resolving to ≥ Grade 2 within 7 days of the most recent dose of test article or was clinically significant irrespective of duration; any ≥ Grade 3 elevation of alanine aminotransferase, aspartate aminotransferase or bilirubin lasting ≥7 days; any test article related toxicity resulting in permanent discontinuation of test article.
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Cycle 1
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Percentage of Participants With Preliminary Satisfactory Response (Complete Response [CR], CR With Incomplete Count Recovery [CRi], Partial Response [PR], or Resistant Disease [RD]) Indicating Disease Stability After First Dose During Phase 1 Dose-Finding
Lasso di tempo: From screening to progressive disease or another induction therapy started, up to approximately 2 years
|
CR was the disappearance of leukemia indicated by <5% marrow blasts and absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by ANC ≥1000/µL and platelets ≥100,000/µL.
C1 extramedullary disease status was required.
CRi was as for CR except with ANC <1000/µL and/or platelets <100,000/µL.
PR was an improved or no worsening of acute lymphocytic leukemia indicated by no peripheral blood blasts, and/or at least a 50% decrease in the marrow blast percentage, compared to pre-treatment value, and marrow blast percentage ≥5% and less than or equal to (≤)25% and/or C2 extramedullary disease status.
RD occurred if a participant survived ≥7 days following completion of initial treatment course and had persistent leukemia in the most recent peripheral blood smear or bone marrow and/or persistent disease involvement at any extramedullary site after completion of therapy.
|
From screening to progressive disease or another induction therapy started, up to approximately 2 years
|
Percentage of Participants With CR or CRi During Phase 2
Lasso di tempo: From screening to progressive disease or another induction therapy started, up to approximately 2 years
|
CR was defined as a disappearance of leukemia as indicated by <5% marrow blasts and the absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by ANC ≥1000/µL and platelets ≥100,000/µL.
C1 extramedullary disease status was required.
CRi was defined as CR except with ANC <1000/µL and/or platelets <100,000/µL.
|
From screening to progressive disease or another induction therapy started, up to approximately 2 years
|
Percentage of Participants With CR, CRi or PR During the Phase 1 Expansion Phase
Lasso di tempo: From screening to progressive disease or another induction therapy started, up to approximately 2 years
|
CR was defined as a disappearance of leukemia as indicated by <5% marrow blasts and the absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by ANC ≥1000/µL and platelets ≥100,000/µL.
C1 extramedullary disease status was required.
CRi was defined as CR except with ANC <1000/µL and/or platelets <100,000/µL.
PR was defined as an improved or no worsening of acute lymphocytic leukemia as indicated by no peripheral blood blasts, and either or both of the following: at least a 50% decrease in the marrow blast percentage, compared to the pre-treatment value, and marrow blast percentage ≥5% and ≤25% and/or C2 extramedullary disease status.
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From screening to progressive disease or another induction therapy started, up to approximately 2 years
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
---|---|---|
Percentage of Participants With CR, CRi or PR in Phase 2
Lasso di tempo: From screening to progressive disease or another induction therapy started, up to approximately 2 years
|
CR was defined as a disappearance of leukemia as indicated by <5% marrow blasts and the absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by ANC ≥1000/µL and platelets ≥100,000/µL.
C1 extramedullary disease status was required.
CRi was defined as CR except with ANC <1000/µL and/or platelets <100,000/µL.
PR was defined as an improved or no worsening of acute lymphocytic leukemia as indicated by no peripheral blood blasts, and either or both of the following: at least a 50% decrease in the marrow blast percentage, compared to the pre-treatment value, and marrow blast percentage ≥5% and ≤25% and/or C2 extramedullary disease status.
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From screening to progressive disease or another induction therapy started, up to approximately 2 years
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Number of Participants With Minimal Residual Disease (MRD) Negativity in Participants Achieving CR and CRi
Lasso di tempo: From screening to progressive disease or another induction therapy started, up to approximately 2 years
|
MRD negativity was defined as <0.01%
mononuclear cells.
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From screening to progressive disease or another induction therapy started, up to approximately 2 years
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Percentage of Participants With CR or CRi by Cytogenetic Category
Lasso di tempo: From screening to progressive disease or another induction therapy started, up to approximately 2 years
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CR was defined as a disappearance of leukemia as indicated by <5% marrow blasts and the absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by ANC ≥1000/µL and platelets ≥100,000/µL.
C1 extramedullary disease status was required.
CRi was defined as CR except with ANC <1000/µL and/or platelets <100,000/µL.
|
From screening to progressive disease or another induction therapy started, up to approximately 2 years
|
Percentage of Participants Who Had a Post-Treatment Stem-Cell Transplant (SCT)
Lasso di tempo: Up to approximately 2 years from first dose
|
Post-treatment SCT rate was defined as the percentage of participants who underwent SCT following treatment with inotuzumab ozogamicin.
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Up to approximately 2 years from first dose
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Progression Free Survival (PFS)
Lasso di tempo: Up to approximately 2 years from first dose
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PFS was defined as the time from Cycle 1 Day 1 to first documentation of PFS event (earliest date of objective progression [PD], treatment discontinuation due to global deterioration of health status, subsequent induction or transplant after best response of PR or resistant disease, relapse after CR or CRi, or death due to any cause).
Participants last known to be 1) alive and 2) without a PFS event, were censored at the date of the last disease assessment that verified lack of event.
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Up to approximately 2 years from first dose
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Duration of Remission (DoR1) for Participants Who Achieved CR or CRi
Lasso di tempo: Up to approximately 2 years from first dose
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DoR1 was defined for participants who responded as the time from the date of first documentation of Complete Hematologic Response (CR or CRi) to the date of the first documentation of relapse after CR or CRi, treatment discontinuation due to global deterioration of health status) or to death due to any cause.
Participants last known to be 1) alive and 2) without a DoR1 event, were censored at the date of the last disease assessment that verified lack of event.
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Up to approximately 2 years from first dose
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Duration of Response (DoR) for Participants Who Achieved CR/CRi or PR
Lasso di tempo: Up to approximately 2 years from first dose
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DoR was defined for participants who respond as the time from the date of first documentation of Hematologic Response (CR, CRi, or PR) to the date of the first documentation of DoR event (earliest date of PD, treatment discontinuation due to global deterioration of health status, first induction therapy or transplant after PR, relapse after CR or CRi or death due to any cause).
Participants last known to be 1) alive and 2) without a DoR event, were censored at the date of the last disease assessment that verified lack of event.
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Up to approximately 2 years from first dose
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Overall Survival (OS)
Lasso di tempo: Up to approximately 2 years from first dose
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OS was defined as the time from Cycle 1 Day 1 to date of death due to any cause.
If death was not documented, censoring occurred at the date at which the participant was last known to be alive.
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Up to approximately 2 years from first dose
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Time to Remission for Participants Who Achieved CR or CRi
Lasso di tempo: Up to approximately 2 years from first dose
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Time to remission was defined as the time from the date of first dose of study drug to the date of first documentation of hematologic remission (CR or CRi) in participants achieving remission during study therapy.
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Up to approximately 2 years from first dose
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Time to Response for Participants Who Achieved CR/CRi or PR
Lasso di tempo: Up to approximately 2 years from first dose
|
Time to response was defined as the time from the date of first dose of study drug to the date of first documentation of hematologic response (CR, CRi, or PR).
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Up to approximately 2 years from first dose
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Time to MRD Negativity for Participants Who Achieved CR or CRi
Lasso di tempo: Screening, Day 21 of Cycles 1 to 6 and up to 4 to 6 weeks after the last dose (up to 34 weeks)
|
Time to MRD negativity was defined as the time from the date of first dose of study drug to the date of first documentation of MRD negativity.
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Screening, Day 21 of Cycles 1 to 6 and up to 4 to 6 weeks after the last dose (up to 34 weeks)
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Duration of Follow-Up
Lasso di tempo: From first dose up to approximately 2 years
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Duration of follow-up was defined as the time from the date of first dose of study drug to the date of last contact for participants known to be alive.
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From first dose up to approximately 2 years
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Percentage of Cluster of Differentiation-22 Positive (CD22+) Leukemic Blasts in Abnormal B Cells in Blood by Visit
Lasso di tempo: Pre-dose on Days 1 and 15 of Cycles 1 and 2, and Day 1 of Cycle 4
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CD22+ leukemic blasts assessed in abnormal B cells from blood (data from central laboratories only).
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Pre-dose on Days 1 and 15 of Cycles 1 and 2, and Day 1 of Cycle 4
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Percentage of CD22+ Leukemic Blasts in Abnormal B Cells in Bone Marrow by Visit
Lasso di tempo: Pre-dose on Days 1 and 15 of Cycles 1 and 2, and Day 1 of Cycle 4
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CD22+ leukemic blasts assessed in abnormal B cells from bone marrow (data from central laboratories only).
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Pre-dose on Days 1 and 15 of Cycles 1 and 2, and Day 1 of Cycle 4
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Messenger Ribonucleic Acid (mRNA) Gene Expression
Lasso di tempo: Predose and postdose on Days 1 and 15 of Cycle 1
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Optional blood samples for pharmacogenomic parameters were collected during Cycle 1 prior to the start of the inotuzumab ozogamicin infusion (0 hours) and 1 hour post-dose (original Final Protocol and Protocol Amendments 1 and 2) or 3 hours post-dose (Protocol Amendments 3 and 4) on Day 1 and Day 15 from those participants who provided consent.
Gene expression analysis of samples collected pre- and post-dosing was performed using 96-gene TaqMan® low density array cards to examine the concordance between clinical outcome and expression of genes such as those involved in DNA damage response, apoptosis, B-cell antigen expression, glutathione metabolism, drug transport and the phosphoinositide 3-kinase/mammalian target of rapamycin pathway.
Expression for each gene was reported as a normalized value, 2^-change in (∆) threshold cycle (Ct), where ∆Ct is Ct^target gene minus Ct^reference genes, averaged.
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Predose and postdose on Days 1 and 15 of Cycle 1
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Collaboratori e investigatori
Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.
Sponsor
Collaboratori
Pubblicazioni e link utili
La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.
Pubblicazioni generali
- Shi Z, Zhu Y, Zhang J, Chen B. Monoclonal antibodies: new chance in the management of B-cell acute lymphoblastic leukemia. Hematology. 2022 Dec;27(1):642-652. doi: 10.1080/16078454.2022.2074704.
- Stock W, Martinelli G, Stelljes M, DeAngelo DJ, Gokbuget N, Advani AS, O'Brien S, Liedtke M, Merchant AA, Cassaday RD, Wang T, Zhang H, Vandendries E, Jabbour E, Marks DI, Kantarjian HM. Efficacy of inotuzumab ozogamicin in patients with Philadelphia chromosome-positive relapsed/refractory acute lymphoblastic leukemia. Cancer. 2021 Mar 15;127(6):905-913. doi: 10.1002/cncr.33321. Epub 2020 Nov 24.
- DeAngelo DJ, Stock W, Stein AS, Shustov A, Liedtke M, Schiffer CA, Vandendries E, Liau K, Ananthakrishnan R, Boni J, Laird AD, Fostvedt L, Kantarjian HM, Advani AS. Inotuzumab ozogamicin in adults with relapsed or refractory CD22-positive acute lymphoblastic leukemia: a phase 1/2 study. Blood Adv. 2017 Jun 27;1(15):1167-1180. doi: 10.1182/bloodadvances.2016001925. eCollection 2017 Jun 27.
Collegamenti utili
Studiare le date dei record
Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.
Studia le date principali
Inizio studio
1 agosto 2011
Completamento primario (Effettivo)
1 agosto 2014
Completamento dello studio (Effettivo)
1 gennaio 2016
Date di iscrizione allo studio
Primo inviato
11 maggio 2011
Primo inviato che soddisfa i criteri di controllo qualità
27 maggio 2011
Primo Inserito (Stima)
1 giugno 2011
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
13 aprile 2017
Ultimo aggiornamento inviato che soddisfa i criteri QC
2 marzo 2017
Ultimo verificato
1 marzo 2017
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Malattie del sistema immunitario
- Neoplasie per tipo istologico
- Neoplasie
- Malattie linfoproliferative
- Malattie linfatiche
- Disturbi immunoproliferativi
- Leucemia
- Leucemia-linfoma linfoblastico a cellule precursori
- Leucemia, linfoide
- Agenti antineoplastici
- Agenti antineoplastici, immunologici
- Antibiotici, Antineoplastici
- Inotuzumab ozogamicina
Altri numeri di identificazione dello studio
- B1931010
- 3129K6-1106 (Altro identificatore: Alias Study Number)
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .
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