Uno studio su GDX012 negli adulti con leucemia mieloide acuta recidivante o refrattaria
Uno studio di fase 1/2a, in aperto, di aumento della dose e di espansione della dose per valutare la sicurezza e l'efficacia di GDX012 in pazienti con leucemia mieloide acuta recidivante o refrattaria
GDX012 is a novel cell therapy developed for the treatment of certain types of cancer, including Acute Myeloid Leukemia (AML). The main aims of the study are to learn how safe GDX012 is, how treatment with GDX012 is tolerated and to determine the best dose of GDX012.
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
The drug being tested in this study is called GDX012. GDX012 is being tested to evaluate the safety and tolerability in adult participants with AML.
The study will enroll approximately 53 patients in two phases, dose escalation and dose expansion.
During Phase 1 (sequential dose escalation), participants will be assigned to one of the following treatment groups each consisting of 3 to 6 participants to receive GDX012 at one of the three dose levels:
- GDX012 Dose 1
- GDX012 Dose 2
- GDX012 Dose 3
Upon completion of Phase 1, 1 to 2 dose levels will be selected for Phase 2a of the study. At the completion of Phase 2a of the study a single dose may be selected by the sponsor and investigators as the recommended phase 2 dose (RP2D) for future study.
This multi-center trial will be conducted in the United States and Japan. The overall time to participate in the study is approximately 14 months.
Tipo di studio
Iscrizione (Effettivo)
Fase
- Fase 2
- Fase 1
Contatti e Sedi
Luoghi di studio
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Kashiwa, Giappone, 277-8577
- National Cancer Center Hospital East
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-
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Alabama
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Birmingham, Alabama, Stati Uniti, 35205
- University of Alabama at Birmingham (UAB) Hospital
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California
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Duarte, California, Stati Uniti, 91010
- City of Hope
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Colorado
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Denver, Colorado, Stati Uniti, 80218
- Sarah Cannon/CBCI
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Illinois
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Chicago, Illinois, Stati Uniti, 60611
- Comprehensive Cancer Center of Northwestern University
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Massachusetts
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Boston, Massachusetts, Stati Uniti, 02215
- Dana-Farber Cancer Institute
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Missouri
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St Louis, Missouri, Stati Uniti, 63110
- Washington University
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New York
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New York, New York, Stati Uniti, 10065
- Thomas Jefferson University
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Ohio
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Cleveland, Ohio, Stati Uniti, 44195
- Cleveland Clinic
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Tennessee
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Nashville, Tennessee, Stati Uniti, 37203
- Tri-Star BMT/Sarah Cannon Nashville
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Texas
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Houston, Texas, Stati Uniti, 77030
- MD Anderson Cancer Center
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
Inclusion criteria:
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Total body weight of ≥40 kg.
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Must have pathologically confirmed relapsed or refractory acute myeloid leukemia (R/R AML) including:
- Relapsed AML is defined as ≥5% blasts in the bone marrow (BM) or peripheral blood at any time after achieving a CR, CRh, Cri, or MLFS.
- Refractory AML is defined as failure to achieve a CR, CRh, Cri, or MLFS after 1 of the following regimens:
i. Two courses of intensive induction chemotherapy. ii. At least 2 cycles of hypomethylating agent (HMA) or low-dose, cytarabine-based combination regimen.
iii. At least 4 cycles of HMA monotherapy.
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During dose escalation, participants must be ineligible for hematopoietic stem cell transplantation (HSCT).
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Must have an anticipated life expectancy of >3 months before lymphodepletion.
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Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
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Participants must have adequate renal, cardiac, hepatic, pulmonary and bone marrow function as defined by the protocol.
Exclusion criteria:
- Diagnosis of acute promyelocytic leukemia.
- Has received or plans to receive any of the excluded therapy/treatment within the specified timeframe before lymphodepleting chemotherapy as defined by the protocol.
- Prior allogeneic HSCT within 3 months of signing informed consent form (ICF) or with ongoing requirement for systemic graft-versus-host therapy.
- Active central nervous system (CNS) involvement.
- History of malignancy other than non-melanoma skin cancer or carcinoma in situ (eg. cervix, bladder, breast) low grade prostate cancer without treatment requirement unless in remission without treatment for ≥2 years.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Non randomizzato
- Modello interventistico: Assegnazione sequenziale
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
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Sperimentale: Phase 1: Dose Escalation of GDX012 (Dose Level 1)
Participants received GDX012 weight-based dose level 1 as an intravenous (IV) infusion on Day 1 of Phase 1, following lymphodepleting chemotherapy. Dose Level 1 was the lowest dose level. |
GDX012 suspension for IV infusion.
Altri nomi:
Chemotherapy agents (fludarabine/cyclophosphamide) as per standard of care. |
|
Sperimentale: Phase 1: Dose Escalation of GDX012 (Dose Level 2)
Participants received GDX012 weight-based dose level 2 as an IV infusion on Day 1 of Phase 1, following lymphodepleting chemotherapy. Dose Level 2 was higher than Dose Level 1. |
GDX012 suspension for IV infusion.
Altri nomi:
Chemotherapy agents (fludarabine/cyclophosphamide) as per standard of care. |
|
Sperimentale: Phase 1: Dose Escalation of GDX012 (Dose Level 3)
Participants received GDX012 weight-based dose level 3 as an IV infusion on Day 1 of Phase 1, following lymphodepleting chemotherapy. Dose Level 3 was higher than Dose Level 2. |
GDX012 suspension for IV infusion.
Altri nomi:
Chemotherapy agents (fludarabine/cyclophosphamide) as per standard of care. |
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Number of Participants With Dose Limiting Toxicities (DLTs) to Determine the Maximum Tolerated Dose (MTD) of GDX012
Lasso di tempo: Up to 30 days post infusion
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DLTs were defined as events occurring by Day 30 after the first GDX012 infusion considered related to GDX012 if they could not be explained by underlying disease, prior therapy, intercurrent illness, or lymphodepleting chemotherapy. Events were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. DLTs included severe non-hematologic toxicities (Grade 3-4, unresolved or involving vital organs), Grade ≥3 graft versus host disease (GvHD) graded per the Mount Sinai Acute GvHD International Consortium recommendations and 2014 National Institutes of Health (NIH) Consensus, Grade 3-4 cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) per American Society for Transplantation and Cellular Therapy (ASTCT) criteria, Grade ≥3 infusion reactions or tumor lysis syndrome (TLS), persistent cytopenia or marrow hypocellularity, and any Grade 5 toxicity attributable to GDX012. |
Up to 30 days post infusion
|
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Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Lasso di tempo: Up to 14 months
|
An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. This includes any newly occurring event or a previous condition that has increased in severity or frequency since the administration of study drug. TEAEs are defined as any AE that begins on or after the initiation of treatment with a study intervention or any existing event that worsens following exposure to the study intervention. |
Up to 14 months
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Percentage of Participants With Disease Response
Lasso di tempo: Up to 14 months
|
Percentage of participants with disease response included participants who achieved complete response (CR), complete response with partial hematologic recovery (CRh), or complete response with incomplete hematologic recovery (CRi), based on responses assessed by the investigator according to the 2022 European Leukemia Net [ELN] response criteria for acute myeloid leukemia (AML). CR was defined as the sum of complete remission and complete remission without measurable residual disease (MRD). CRh was defined as the sum of CRh and CRhMRD-. CRi was defined as the sum of CRi and CRiMRD-. |
Up to 14 months
|
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Percentage of Participants With Measurable Residual Disease (MRD) Negative Status as Determined by Flow Cytometry
Lasso di tempo: Up to 14 months
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The MRD negative status was defined as (less than) <0.1% detectable disease based on local assessment of bone marrow and/or blood. |
Up to 14 months
|
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Duration of Response (DOR)
Lasso di tempo: Up to 14 months
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DOR was planned to be assessed for participants with CR, CRh, or CRi and was defined as the time from the date of first documented CR, CRh, or CRi to the date of first documented relapse or death from any cause, whichever comes first. CR was defined as the sum of Complete Remission and Complete Remission without MRD. CRh was defined as the sum of CRh and CRhMRD-. CRi was defined as the sum of CRi and CRiMRD- . |
Up to 14 months
|
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Event-free Survival (EFS)
Lasso di tempo: Up to 14 months
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EFS was defined as the time from the date of the first GDX012 administration to the date of treatment failure, relapse for those who achieved CR, CRh, or CRi, or death from any cause, whichever came first. CR was defined as the sum of Complete Remission and Complete Remission without MRD (CRMRD-). CRh was defined as the sum of CRh and CRhMRD-. CRi was defined as the sum of CRi and CRiMRD-. EFS was analyzed using the Kaplan-Meier method. |
Up to 14 months
|
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Overall Survival (OS)
Lasso di tempo: Up to 14 months
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OS was defined as the time from the date of the first GDX012 administration to the date of death from any cause. Participants without documentation of death at the time of analysis were censored at the last contact date. OS was analyzed using the Kaplan-Meier method. |
Up to 14 months
|
Collaboratori e investigatori
Sponsor
Investigatori
- Direttore dello studio: Medical Director, Takeda
Pubblicazioni e link utili
Collegamenti utili
- <p>Click here to ask Takeda's chatbot for comprehensive and easy-to-understand information about clinical trials - even across products and indications - in your local language.</p>
- <p>Click here for more information about this trial in easy-to-understand language, including a Plain Language Summary of the results if the trial has been completed.</p>
Studiare le date dei record
Studia le date principali
Inizio studio (Effettivo)
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Effettivo)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
- TAK-012-1501
- jRCT2033240022 (Identificatore di registro: jRCT)
Piano per i dati dei singoli partecipanti (IPD)
Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?
Descrizione del piano IPD
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
Criteri di accesso alla condivisione IPD
IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
Tipo di informazioni di supporto alla condivisione IPD
- STUDIO_PROTOCOLLO
- LINFA
- ICF
- RSI
Informazioni su farmaci e dispositivi, documenti di studio
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