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Ibrutinib Combined With Rituximab for Treatment of Relapsed Refractory MYD88 and CD79A/B (or CD79B Alone) DLBCL Who Have Received at Least Two Prior Therapies

3 agosto 2021 aggiornato da: Shi Yuankai, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Phase II, Multi-Center Study to Evaluate the Efficacy and Safety of Ibrutinib Combined With Rituximab for Treatment of Relapsed Refractory MYD88 and CD79A/B (or CD79B Alone) DLBCL Who Have Received at Least Two Prior Therapies

The purpose of this study is to evaluate the efficacy and safety of Ibrutinib Combined With Rituximab in Relapsed Refractory MYD88 and CD79A/B (or CD79B Alone) DLBCL Who Have Received at Least Two Prior Therapies.

Panoramica dello studio

Stato

Non ancora reclutamento

Condizioni

Intervento / Trattamento

Descrizione dettagliata

Recent studies have found that about 30% of DLBCL have mutations in MYD88 and/or CD79A/B genes. MYD88 and CD79A/B protein molecules belong to two signal transduction pathways, which regulate B cell proliferation. Both MYD88 and CD79A/B gene mutations can abnormally activate BTK located downstream of MYD88 and CD79A/B, leading to over activation and proliferation of B cells.

Ibrutinib is the first generation of oral BTKi, which may theoretically inhibit the tumorigenesis of DLBCL with abnormal BTK activation caused by mutations in MYD88 and CD79A/B genes.

A phase II clinical study of ibrutinib monotherapy in the treatment of relapsed and refractory DLBCL showed that the effective rate of ibutinib for single CD79B mutation was 55.5% (5/9 cases), and that for both CD79B and MYD88 mutations was 80% (4/5 cases). About 40 ~ 50% of primary central nervous system large B cell lymphoma (PCNSL) have CD79B and MYD88 mutations. A small sample study found that the overall response rate (ORR) for the treatment of relapsed and refractory PCNSL with ibrutinib was 77% (10/13). An expanded sample study of 44 cases of PCNSL treated with ibrutinib found that the ORR is 52% and progression-free survival (PFS) is 4.8 months. These results suggest that ibrutinib may be more effective in DLBCL with MYD88 and CD79A/B or CD79B mutations.

The relationship between mutations in MYD88 and CD79B and therapeutic sensitivity of ibrutinib can not be simply categorized, because abnormalities in other genes of B cell signaling pathway, such as CARD11, TNFAIP3, CXCR4, JAK1 and PIM1, may also affect the efficacy of ibrutinib. Therefore, it is necessary to comprehensively analyze the gene abnormalities of other B cell related signaling pathways, such as downstream signal of Bruton kinase, CXCR, JAK-STAT, and NFKB, to find out the most effective group of DLBCL patients treated with ibrutinib.

This phase II, single-arm, open-label, multi-center clinical trial will evaluate the efficacy and safety of ibrutinib combined with rituximab in treating relapsed refractory MYD88 and CD79A/B (or CD79B alone) DLBCL who have received at least two prior therapies. The study will also explore the relationship between MYD88 and/or CD79A/B and efficacy, and detect the gene abnormality by Next Generation Sequencing (NGS) and evaluate the relationship between other gene abnormality and efficacy.

Tipo di studio

Interventistico

Iscrizione (Anticipato)

20

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.

Contatto studio

Backup dei contatti dello studio

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

Da 18 anni a 80 anni (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

Inclusion Criteria:

  1. Participants must be able to understand and be willing to sign a written informed consent document;
  2. Men and woman who are at least 18 years of age on the day of consenting to the study;
  3. According to the WHO 2016 classification criteria, pathologically confirmed CD20+diffuse large B-cell lymphoma;
  4. Patients with MYD88 and CD79A/B mutations or CD79B alone;
  5. Relapse or progression after treatment with at least two prior therapies;
  6. There is at least one measurable lesion, defined as a two-path measurable, intraductal lesion short neck >1.5cm, extranodal lesion short diameter >1.0cm;
  7. Eastern Cooperative Oncology Group (ECOG) performance status =< 2

  8. Blood routine examination meets the following criteria:

    Neutrophil count ≥ 1.0 x 109 / L; Platelet ≥ 75 x 109 / L; Hemoglobin ≥ 10.0 g / dL;

  9. The main organ function meets the following criteria:

    Aspartate aminotransferase and alanine aminotransferase ≤ 2.0 times the upper limit of normal value; Bilirubin ≤ 2.0 mg / dL; Creatinine clearance rate ≥ 60 mL / min;

  10. Must agree to effective contraception

Exclusion Criteria:

  1. Transformed diffuse large B-cell lymphoma;
  2. HBV DNA positive or HCV RNA positive;
  3. Patient is known to have an uncontrolled active systemic infection;
  4. Left ventricular ejection fraction < 40%;
  5. Previous autoimmune diseases, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, dry syndrome, ankylosing spondylitis, etc;
  6. Immunosuppressive drugs are being or have been used in the past;
  7. Known hypersensitivity to the study drug or any of its excipients;
  8. There are other active malignant tumors that may interfere with this study requiring treatment;
  9. Known history of human immunodeficiency virus (HIV) infection;
  10. Previous autologous stem cell transplantation or allogeneic hematopoietic stem cell transplantation;
  11. The investigator judges that the patient has other inappropriate circumstances.

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
  • Assegnazione: N / A
  • Modello interventistico: Assegnazione di gruppo singolo
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: Ibrutinib Combined With Rituximab

Induction therapy: Ibrutinib 560mg administered oral once a day of each 21-day cycle for 6 cycles. Rituximab 375mg/m² administered intravenously (IV) on Day 1 of each 21-day cycle for 6 cycles.

Maintenance therapy: Ibrutinib 560mg administered oral once a day of each 56-day cycle for 6 cycles. Rituximab 375mg/m² administered intravenously (IV) on Day 1 of each 56-day cycle for 6 cycles.
Droga: Ibrutinib Combined With Rituximab

Drug: ibrutinib ibrutinib 560mg administered orally once daily. Other Name: Imbruvica

Drug: rituximab rituximab 375mg/m² administered intravenously (IV)

Altri nomi:
  • Imbruvica Combined With Rituximab

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Objective Response Rate(ORR)
Lasso di tempo: 24 months after the last patient's enrollment
The ORR includes complete response and partial response. The treatment response assessments are as follows: Evaluation of treatment response are performed every 2 cycles followed the International Lymphoma Collaborative Group guidelines.
24 months after the last patient's enrollment

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Progression Free Survival (PFS)
Lasso di tempo: at 6 month and 1 year
From the date into this study to disease progression or death
at 6 month and 1 year
Overall Survival (OS)
Lasso di tempo: at 6 month and 1 year
From the date into this study to death
at 6 month and 1 year
Event Free Survival (EFS)
Lasso di tempo: at 6 month and 1 year
From the date into this study to disease progression, relapse from CR as assessed by the investigator, completion of study treatment followed by subsequent systemic anti-lymphoma therapy, or death from any cause, whichever occurred first.
at 6 month and 1 year
Adverse events
Lasso di tempo: 24 months after the last patient's enrollment
AEs will be evaluated using the NCI CTCAE v4.0.
24 months after the last patient's enrollment
Assessment of the correlation between MYD88 and/or CD79A/B or other gene abnormality and efficacy.
Lasso di tempo: 24 months after the last patient's enrollment
To explore the relationship between MYD88 and/or CD79A/B and efficacy and to detect the gene abnormality by Next Generation Sequencing (NGS) and evaluate the relationship between other gene abnormality and efficacy.
24 months after the last patient's enrollment

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Investigatori

  • Investigatore principale: Yuankai Shi, M.D., Cancer Hospital Chinese Academy of Medical Sciences & Peking Union Medical College

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 (Anticipato)

1 ottobre 2021

Completamento primario (Anticipato)

1 aprile 2022

Completamento dello studio (Anticipato)

1 luglio 2025

Date di iscrizione allo studio

Primo inviato

3 agosto 2021

Primo inviato che soddisfa i criteri di controllo qualità

3 agosto 2021

Primo Inserito (Effettivo)

6 agosto 2021

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

6 agosto 2021

Ultimo aggiornamento inviato che soddisfa i criteri QC

3 agosto 2021

Ultimo verificato

1 agosto 2021

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • NCC2613

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

No

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

No

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

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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