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Study of SyB L-0501 in Combination With Rituximab to Treat Relapsed/Refractory Diffuse Large B-Cell Lymphoma

29 mai 2013 mis à jour par: SymBio Pharmaceuticals

A Multinational, Multicenter, Open-Label Phase II Study of SyB L-0501 in Combination With Rituximab in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

The purpose of this study is to determine the efficacy of SyB L-0501 in combination with rituximab in patients with relapsed/refractory diffuse large B-cell lymphoma.

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Description détaillée

Primary Objective is to determine the efficacy, as measured by overall response rate on the basis of Revised Response Criteria for Malignant Lymphoma, of SyB L-0501 at 120 mg/m^2/day on day2 and 3 in combination with rituximab at 375 mg/m^2 on day 1 of each 21-day cycle in patients with relapsed/refractory diffuse large B-cell lymphoma.

Type d'étude

Interventionnel

Inscription (Réel)

63

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

  • Corée, République de
    • Busan
      • Seo-gu, Busan, Corée, République de
    • Daegu
      • Jung-gu, Daegu, Corée, République de
    • Gyeonggi-do
      • Goyang-si, Gyeonggi-do, Corée, République de
    • Jeonnam
      • Hwasun-gun, Jeonnam, Corée, République de
    • Seoul
      • Gangnam-gu, Seoul, Corée, République de
      • Seodaemun-gu, Seoul, Corée, République de
      • Songpa-gu, Seoul, Corée, République de
  • Japon
      • Akita, Japon
      • Fukuoka, Japon
      • Kagoshima, Japon
      • Kyoto, Japon
    • Aichi
      • Nagoya, Aichi, Japon
    • Ehime
      • Matsuyama, Ehime, Japon
    • Fukuoka
      • Kurume, Fukuoka, Japon
    • Gunma
      • Maebashi, Gunma, Japon
    • Hokkaido
      • Sapporo, Hokkaido, Japon
    • Ishikawa
      • Kanazawa, Ishikawa, Japon
    • Kanagawa
      • Isehara, Kanagawa, Japon
    • Kumamoto
      • Ninomaru, Kumamoto, Japon
    • Miyagi
      • Sendai, Miyagi, Japon
    • Okayama
      • Kita-ku, Okayama, Japon
      • Kurashiki, Okayama, Japon
    • Saitama
      • Hidaka, Saitama, Japon
    • Shimane
      • Izumo, Shimane, Japon
    • Tokyo
      • Chuo-ku, Tokyo, Japon

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

20 ans à 75 ans (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria:

  • Patients with documented Cluster of differentiation 20 (CD20)-positive for lymphoma cells
  • Patients with measurable lesions
  • Patients with measurable lesions >1.5 cm in major axes
  • Relapsed or refractory after 1 to 3 prior therapeutic treatments for diffuse large B-cell lymphoma.
  • Patients who are expected to survive for at least 3 months
  • Patients aged from 20 to 75 years at the time informed consent is obtained
  • Performance Status (P.S.) of 0 to 1 at initial administration of the study drug
  • Patients with adequately maintained organ functions
  • Patients capable of personally giving voluntary informed consent in writing to participate in the study

Exclusion Criteria:

  • Patients who have been without treatment for less than 3 weeks after prior treatment
  • Patients who can be candidates for autologous peripheral blood stem cell transplantation at the discretion of the investigator.
  • Patients who received adequate prior treatments and did not respond to any of them.
  • Patients with central nervous system (CNS) involvement or patients with clinical symptoms suggestive of CNS involvement.
  • Patients with serious, active infections
  • Patients with serious complications
  • Patients with complications or medical history of serious cardiac disease
  • Patients with serious gastrointestinal symptoms
  • Patients with malignant pleural effusion, cardiac effusion, or ascites retention
  • Patients positive for hepatitis B surface (HBs) antigen, hepatitis C virus (HCV) antibody, or HIV antibody
  • Patients with serious bleeding tendencies
  • Patients with a fever of 38.0°C or higher
  • Patients with, or confirmed in the past to have had, interstitial pneumonia, pulmonary fibrosis, or pulmonary emphysema
  • Patients with active multiple primary cancer or patients with a history of other malignant cancer within the past 5 years, except for basal cell cancer of the skin, squamous cell cancer, or cervical cancer in situ
  • Patients with, or confirmed in the past to have had, autoimmune hemolytic anemia
  • Patients who received SyB L-0501 in the past
  • Patients who received cytokine preparation such as erythropoietin or granulocyte colony-stimulating factor (G-CSF) or blood transfusions within 2 weeks before the examination at registration for this study
  • Patients who received other investigational products or unapproved medication within 3 months before registration in this study

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: Non randomisé
  • Modèle interventionnel: Affectation à un seul groupe
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: SyB L-0501
Médicament: SyB L-0501

The administration of SyB L-0501 at 120 mg/m^2/day by intravenous infusion on day 2 and 3 of each 21-day cycle with up to 6 cycles. Dose modifications are permitted from 2nd cycle according to dose reduction schedule.

SyB L-0501 60 mg/m^2, 90 mg/m^2 or 120 mg/m^2/day on Day 2 and Day 3 will be followed by 18 days of observation.

Autres noms:
  • Chlorhydrate de bendamustine
Médicament: Rituximab
The administration of rituximab at 375 mg/m^2/day by intravenous infusion on day 1 of each 21-day cycle with up to 6 cycles. Dose modifications are not permitted.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
The Overall Response Rate [Complete Response (CR) + Partial Response (PR)] Determined on the Basis of Revised Response Criteria for Malignant Lymphoma
Délai: up to 30 weeks

CR: Disappearance of all evidence of disease. PR: Regression of measurable disease and no new sites.

For the criteria for CR, See Outcome measure 2 description.

The criteria for PR is as below.

Nodal Masses:

more than 50% decrease in sum of the product of the perpendicular diameters (SPD) of up to 6 largest dominant masses; no increase in size of other nodes

  1. FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site
  2. Variably FDG-avid or PET negative; regression on CT

Spleen, Liver:

more than 50% decrease in SPD of nodules (for single nodule in greatest transverse diameter); no increase in size of liver or spleen

Bone Marrow:

Irrelevant if positive prior to therapy; cell type should be specified
up to 30 weeks

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
The Complete Response (CR) Rate Determined on the Basis of Revised Response Criteria for Malignant Lymphoma
Délai: up to 30 weeks

The criteria for CR is as below

Nodal Masses:

  1. fluorodeoxy glucose (FDG)-avid or positron emission tomography (PET) positive prior to therapy; mass of any size permitted if PET negative
  2. Variably FDG-avid or PET negative; regression to normal size on computed tomography (CT)

Spleen, Liver:

Not palpable, nodules disappeared

Bone Marrow:

Infiltrate cleared on repeat biopsy; if indeterminate by morphology, immunohistochemistry should be negative
up to 30 weeks
Progression Free Survival (PFS)
Délai: up to 30 weeks

PFS = day of the first PFS event - day of start of study treatment + 1

The definitions of PFS event are as below.

  1. PD according to overall response on the basis of Revised Response Criteria for Malignant Lymphoma

    PD: Any new lesion or increase by ≥50% of previously involved sites from nadir. Nodal masses; 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. Lesions PET positive if FDG-avid lymphoma or PET positive prior to therapy. Spleen, Liver; ≥50% increase from nadir in the SPD of any previous lesions. Bone marrow; New or recurrent involvement

  2. Disease progression during treatment period
  3. Disease progression during follow up period
  4. Start of treatment of new lesion
  5. Occurrence of other multiple malignant tumors
  6. Death
up to 30 weeks
Number of Subjects With Adverse Event
Délai: up to 30 weeks
up to 30 weeks
Number of Adverse Events
Délai: up to 30 weeks
up to 30 weeks
Number of Subjects With Abnormality (Grade ≥3) in Laboratory Test Values
Délai: up to 30 weeks

Abnormalities in laboratory test values in overall study period were analyzed. Severity of abnormalities were evaluated using Common Terminology Criteria for Adverse Events (CTCAE).

grade 1 : mild grade 2 : moderate grade 3 : severe grade 4 : life threatening or disabling grade 5 : death related to adverse event
up to 30 weeks
Number of Subjects With Grade ≥3 Physical Examination Finding
Délai: up to 30 weeks
up to 30 weeks
Concomitant Medication Usage
Délai: up to 30 weeks
up to 30 weeks
The Maximum Concentration (Cmax) of Unchanged SyB L-0501 in Japan
Délai: Prior to and 30 min after start of administration, and 0, 30, 60, 120 min after completion of administration on Day 2 of the 1st cycle
Prior to and 30 min after start of administration, and 0, 30, 60, 120 min after completion of administration on Day 2 of the 1st cycle
The Maximum Drug Concentration Time (Tmax) of Unchanged SyB L-0501 in Japan
Délai: Prior to and 30 min after start of administration, and 0, 30, 60, 120 min after completion of administration on Day 2 of the 1st cycle
Prior to and 30 min after start of administration, and 0, 30, 60, 120 min after completion of administration on Day 2 of the 1st cycle
The Area Under the Curve (AUC) for Unchanged SyB L-0501 in Japan
Délai: Prior to and 30 min after start of administration, and 0, 30, 60, 120 min after completion of administration on Day 2 of the 1st cycle
Prior to and 30 min after start of administration, and 0, 30, 60, 120 min after completion of administration on Day 2 of the 1st cycle
The Half-life Period (t1/2) of Unchanged SyB L-0501 in Japan
Délai: Prior to and 30 min after start of administration, and 0, 30, 60, 120 min after completion of administration on Day 2 of the 1st cycle
Prior to and 30 min after start of administration, and 0, 30, 60, 120 min after completion of administration on Day 2 of the 1st cycle
The Maximum Concentration (Cmax) of Unchanged SyB L-0501 in Korea
Délai: Prior to and 30 min after start of administration, and 0, 30, 60, 120 min after completion of administration on Day 2 of the 1st cycle
Prior to and 30 min after start of administration, and 0, 30, 60, 120 min after completion of administration on Day 2 of the 1st cycle
The Maximum Drug Concentration Time (Tmax) of Unchanged SyB L-0501 in Korea
Délai: Prior to and 30 min after start of administration, and 0, 30, 60, 120 min after completion of administration on Day 2 of the 1st cycle
Prior to and 30 min after start of administration, and 0, 30, 60, 120 min after completion of administration on Day 2 of the 1st cycle
The Area Under the Curve (AUC) for Unchanged SyB L-0501 in Korea
Délai: Prior to and 30 min after start of administration, and 0, 30, 60, 120 min after completion of administration on Day 2 of the 1st cycle
Prior to and 30 min after start of administration, and 0, 30, 60, 120 min after completion of administration on Day 2 of the 1st cycle
The Half-life Period (t1/2) of Unchanged SyB L-0501 in Korea
Délai: Prior to and 30 min after start of administration, and 0, 30, 60, 120 min after completion of administration on Day 2 of the 1st cycle
Prior to and 30 min after start of administration, and 0, 30, 60, 120 min after completion of administration on Day 2 of the 1st cycle

Collaborateurs et enquêteurs

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

Parrainer

SymBio Pharmaceuticals

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

1 avril 2010

Achèvement primaire (Réel)

1 octobre 2011

Achèvement de l'étude (Réel)

1 octobre 2011

Dates d'inscription aux études

Première soumission

1 mai 2010

Première soumission répondant aux critères de contrôle qualité

6 mai 2010

Première publication (Estimation)

7 mai 2010

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Estimation)

4 juillet 2013

Dernière mise à jour soumise répondant aux critères de contrôle qualité

29 mai 2013

Dernière vérification

1 mai 2013

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • 2010001

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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