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High Dose Rituximab for Initial Treatment of Indolent B-Cell Lymphomas

9 mai 2017 mis à jour par: Jeremy Abramson, MD, Massachusetts General Hospital

Phase II Trial of Increased Dose Rituximab Plus Maintenance Rituximab for Initial Systemic Treatment of Indolent B-Cell Lymphomas

The purpose of this clinical trial is to see if increased doses of rituximab are safe and effective for the initial treatment of indolent B-cell lymphomas. Rituximab (Rituxan) is a type of drug called an "antibody" that specifically targets B-cell lymphoma cells, and is approved by the FDA for the treatment of indolent B-cell non-hodgkin lymphomas and certain other types of non-hodgkin lymphomas. Standard doses currently used may not be achieving maximal efficacy. Higher doses have been shown to be safe in other clinical trials, and may offer superior efficacy to the current standard dose. This trial also employs intermittent maintenance doses of rituximab at the standard dose, which has been shown to prolong remissions and survival in patients with relapsed indolent B-cell lymphomas. This trial is designed to show that higher dose rituximab plus maintenance rituximab can achieve similarly good results to chemotherapy approaches, but without chemotherapy-related toxicity.

Aperçu de l'étude

Statut

Complété

Intervention / Traitement

Description détaillée

  • All participants will receive increased-dose rituximab through a vein in the arm once a week for 4 weeks (on Days 1, 8, 15, and 22 of the initial 28-day study cycle). This first cycle of study treatment is called the Induction Phase. If the participant responds well to the Induction Phase, they then may continue to the Maintenance Therapy Phase, where they will receive a lower dose of rituximab once every three months for up to 2 years.
  • During the Induction Phase, the following procedures will take place before the participant receives each dose of rituximab: medical review, physical exam, performance status, and ECG. Blood tests will be drawn about 30-60 minutes after the first dose of rituximab on Day 1. Samples will be drawn immediately before each dose and again 30-60 minutes after each dose on Days 1, 8, 15 and 22.
  • During the Maintenance Therapy Phase, the following procedures will take place before the participant receives each dose of rituximab: medical review, physical exam, performance status, ECG, blood tests and response assessments by CT scan.

Type d'étude

Interventionnel

Inscription (Réel)

40

Phase

  • Phase 2

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

    • Massachusetts
      • Boston, Massachusetts, États-Unis, 02115
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, États-Unis, 02114
        • Massachusetts General Hospital

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans et plus (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria:

  • Indolent B-Cell NHL of the following histologies:

    1. Follicular lymphoma (grades 1-3A);
    2. marginal zone lymphoma (extranodal, nodal or splenic):

      • Extranodal marginal zone lymphomas (MALT lymphomas) may not be candidates for cure with antibiotics or local radiotherapy. Patients who have failed antibiotics or local therapy are eligible for the protocol as long as they have measurable disease and are naive to chemotherapy and monoclonal antibody;
      • splenic marginal zone lymphoma patients may have received prior splenectomy as long as they have measureable disease and are naive to chemotherapy and monoclonal antibody therapy;
    3. Small lymphocytic lymphoma (must have less than 5000 circulating clonal B-lymphocytes);
    4. Indolent CD20+ B-cell lymphoma not otherwise specified with CD20+ expression
  • Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as 20mm or greater with conventional techniques or as 10mm or greater with spiral CT scan
  • No previous chemotherapy, antibody therapy or radioimmunotherapy for NHL. Patients previously treated with external bean radiation alone, surgery, or with antibiotics are eligible
  • 18 years of age or older
  • Life expectancy of greater than 3 months
  • ECOG performance status of 2 or less
  • Adequate bone marrow function
  • Use of adequate contraception

Exclusion Criteria:

  • Prior chemotherapy, monoclonal antibody therapy or radioimmunotherapy for lymphoma
  • Receiving any other investigational agent
  • Known brain metastases
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to rituximab
  • HIV positivity
  • Active hepatitis B infection
  • Candidate for curative radiotherapy, unless radiation therapy is considered too toxic (as in abdominal disease), or is refused by the patient
  • NYHA Classification III or IV disease
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection that is not optimally treated with antibiotics, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women
  • Individuals with a history of a different malignancy except for the following circumstances:

    1. disease-free for at least 1 year and are deemed by the investigator to be at low risk for recurrence of that malignancy;
    2. localized prostate cancer, prostate cancer with elevated PSA but no measurable disease on CT scans or bone scan, cervical cancer in situ; and
    3. non-melanoma skin cancers

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: N / A
  • Modèle interventionnel: Affectation à un seul groupe
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Autre: rituximab
single-arm, open-label, interventional
Increased dose (750 mg/m2) intravenously for 4 weekly doses followed by maintenance dosing once every three months for up to 2 years. Maintenance dose is standard (375 mg/m2).
Autres noms:
  • Rituxan

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Determine Complete Response Rate (CRR) of Increased Dose Rituximab in Indolent B-cell Lymphomas
Délai: after a median number of 8 maintenance cycles, up to 24 weeks

CR requires all of the following:

  1. Regression to normal size on CT (≤ 1.5 cm in their greatest transverse diameter for nodes ≥ 1.5 cm before therapy). Previously involved nodes that were 1.1 to 1.5 cm in their greatest transverse diameter before treatment must have decreased to <1 cm in their greatest transverse diameter after treatment, or by more than 75% in the sum of the products of the greatest diameters (SPD).
  2. The spleen, if considered to be enlarged before therapy on the basis of a CT scan, must have regressed in size and must not be palpable on physical examination.
  3. If bone marrow is known to be involved at the beginning, then repeat biopsy documents clearance
after a median number of 8 maintenance cycles, up to 24 weeks

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Overall Response Rate (ORR)
Délai: after a median number of 8 maintenance cycles, up to 24 weeks

Complete Response (CR): see definition in primary outcome

Partial Response (PR):

  1. ≥50% decrease in SPD of up to 6 largest dominant masses
  2. No new sites of disease or increase in the size of the other nodes, liver, or spleen.
  3. Splenic and hepatic nodules must regress by at least 50% in the SPD.

Overall Response (OR) = CR + PR.

after a median number of 8 maintenance cycles, up to 24 weeks
Progression-free Survival (PFS)
Délai: 5 years

Progressive Disease (PD) or Relapsed Disease (RD):

  1. Appearance of a new lesion(s) > 1.5 cm in any axis, ≥ 50% increase in SPD of more than one node, or ≥50% increase in longest diameter of a previously identified node > 1 cm in short axis.
  2. >50% increase from nadir in the SPD of any previous lesions PFS is number of participants who have not died or had PD or RD.
5 years
Incidence of Severity of Infusion Reactions, Infections and Neutropenia
Délai: 24 months
Toxicity grades: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening
24 months

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

1 juillet 2009

Achèvement primaire (Réel)

1 octobre 2010

Achèvement de l'étude (Réel)

1 août 2015

Dates d'inscription aux études

Première soumission

6 mai 2009

Première soumission répondant aux critères de contrôle qualité

7 mai 2009

Première publication (Estimation)

8 mai 2009

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

9 juin 2017

Dernière mise à jour soumise répondant aux critères de contrôle qualité

9 mai 2017

Dernière vérification

1 mai 2017

Plus d'information

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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