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Study Evaluating Inotuzumab Ozogamicin (CMC-544) Plus Rituximab In Diffuse Large B-Cell Non-Hodgkin's Lymphoma

30. oktober 2017 opdateret af: Pfizer

An Open-label, Single-arm, Phase 2 Study Of Inotuzumab Ozogamicin Plus Rituximab In Subjects With Relapsed/Refractory Cd22-positive Diffuse Large B-cell Lymphoma, Eligible For Autologous Stem Cell Transplantation

The purpose of this study is to evaluate inotuzumab ozogamicin in combination with rituximab prior to an autologous stem cell transplant (aSCT) in patients with relapsed/refractory diffuse large B-cell Non-Hodgkin's lymphoma.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

64

Fase

  • Fase 2

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Det Forenede Kongerige
      • Manchester, Det Forenede Kongerige, M20 4BX
        • The Christie NHS Foundation Trust
      • Manchester, Det Forenede Kongerige, M20 4BX
        • Christie Hospital
  • Forenede Stater
    • Illinois
      • Maywood, Illinois, Forenede Stater, 60153
        • Loyola University Medical Center, Foster G. McGraw Hospital and Satellites
    • Massachusetts
      • Boston, Massachusetts, Forenede Stater, 02111
        • Tufts Medical Center
    • Michigan
      • Ann Arbor, Michigan, Forenede Stater, 48109
        • University Of Michigan Comprehensive Cancer Center
    • Missouri
      • Saint Louis, Missouri, Forenede Stater, 63110
        • Washington University School of Medicine
      • Saint Louis, Missouri, Forenede Stater, 63110-1094
        • Barnes-Jewish Hospital
      • Saint Peters, Missouri, Forenede Stater, 63376
        • Siteman Cancer Center
    • New Jersey
      • Hackensack, New Jersey, Forenede Stater, 07601
        • Hackensack University Medical Center
      • Hackensack, New Jersey, Forenede Stater, 07601
        • John Theurer Cancer Center, Hackensack University Medical Center
      • Hackensack, New Jersey, Forenede Stater, 07601-1941
        • John Theurer Cancer Center (JTCC) at Hackensack University Medical Center (HUMC)
      • Hackensack, New Jersey, Forenede Stater, 07601-2105
        • John Theurer Cancer Center (JTCC) at Hackensack University Medical Center (HUMC)
      • Hackensack, New Jersey, Forenede Stater, 07601
        • John Theurer Cancer Center (JTCC) at Hackensack University Medical Center (HUMC)
    • New York
      • New York, New York, Forenede Stater, 10065
        • Memorial Sloan - Kettering Cancer Center
    • Pennsylvania
      • Hershey, Pennsylvania, Forenede Stater, 17033-0850
        • Penn State Milton S Hershey Medical Center
    • Texas
      • Dallas, Texas, Forenede Stater, 75390
        • UT Southwestern Medical Center
      • Dallas, Texas, Forenede Stater, 75235
        • Zale Lipshy University Hospital
      • Dallas, Texas, Forenede Stater, 75235
        • UT Southwestern University Hospital - St. Paul
      • Houston, Texas, Forenede Stater, 77030
        • University of Texas, MD Anderson Cancer Center
      • Houston, Texas, Forenede Stater, 77030-4009
        • The University of Texas, M. D. Anderson Cancer Center
      • San Antonio, Texas, Forenede Stater, 78229
        • Methodist Healthcare System of
    • Wisconsin
      • Madison, Wisconsin, Forenede Stater, 53792-0001
        • University of Wisconsin Hospital and Clinics
      • Madison, Wisconsin, Forenede Stater, 53792
        • Pharmaceutical Research Center
  • Frankrig
      • Lille, Frankrig, 59037
        • CHRU de Lille Hopital Claude Huriez
      • Marseille, Frankrig, 13273
        • Institut Paoli Calmettes
      • Montpellier Cedex 5, Frankrig, 34295
        • CHU Saint-Eloi
      • Paris, Frankrig, 75010
        • Hopital Saint Louis
      • Pessac, Frankrig, 33604
        • Hôpital Haut-Lévêque
      • Pierre-Benite cedex 114, Frankrig, 69495
        • CH Lyon sud
      • Pierre-benite Cedex, Frankrig, 69495
        • CH Lyon sud
      • Strasbourg, Frankrig, 67098
        • Departement d'Hematologie et d'Oncologie-
  • Korea, Republikken
      • Seoul, Korea, Republikken, 120-752
        • Severance Hospital, Yonsei University Health System
    • Gangnam-gu
      • Seoul, Gangnam-gu, Korea, Republikken, 135-710
        • Samsung Medical Center
    • Seoul/korea
      • Seoul, Seoul/korea, Korea, Republikken, 138-736
        • Asan Medical Center
  • Singapore
      • Singapore, Singapore, 169608
        • Singapore General Hospital
  • Tyskland
      • Berlin, Tyskland, 13353
        • Charite Campus Virchow-Kilinikum-

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

Inclusion Criteria:

  • CD20/CD22-positive diffuse large B-cell NHL that has relapsed after 1 or 2 prior therapies; one prior therapy must include anthracyclines and one must include rituximab in combination with chemotherapy
  • Relapsed/disease progression within 12 months after start of prior therapy and/or secondary International Prognostic Index (sIPI) score greater than 1
  • Eligible for autologous stem cell transplant (aSCT)

Exclusion Criteria:

  • Prior allogeneic hematopoietic stem cell transplant
  • Within 6 months prior to test article: autologous transplant, treatment with anti-CD22 antibodies, radio-immunotherapy
  • Veno-occlusive disease or sinusoidal obstruction syndrome, chronic liver disease, systemic vasculitides, current or chronic hepatitis B or C infection

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Ikke-randomiseret
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Rituximab 375 mg/m^2 + Inotuzumab Ozogamicin 1.8 mg/m^2
Inotuzumab ozogamicin, in combination with rituximab, will be administered to patients with relapsed/refractory diffuse large B-cell Non-Hodgkin's lymphoma prior to an autologous stem cell transplant (aSCT).
Medicin: inotuzumab ozogamicin (CMC-544)
1.8 mg/m^2 every 21 days by intravenous infusion, 3 to 6 doses
Andre navne:
  • cmc-544
Medicin: rituximab
375 mg/m^2 two days before cycle 1 by intravenous infusion; 375 mg/m^2 every 21 days by intravenous infusion, 3 to 6 doses

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) After 3 Cycles of Inotuzumab Ozogamicin Plus Rituximab Therapy
Tidsramme: Up to 2 years (9 weeks of 3 21-day cycles and every 3 to 6 months during the long-term follow-up period)
Response criteria based on National Cancer Institute (NCI) International Response Criteria for non-Hodgkin's lymphoma. CR: no detectable clinical & radiographic evidence of disease/disease-related symptoms; lymph nodes/nodal masses regressed to normal size (less than or equal to [≤] 1.5 cm in greatest transverse diameter for nodes greater than [>] 1.5 cm pre-therapy); spleen & other organs (if enlarged pre-therapy) regressed in size & spleen not palpable on physical examination; repeat bone marrow infiltrate clear. PR: > or equal to (≥) 50% decrease in sum of product diameters (SPD) of 6 largest dominant nodes/nodal masses; no increase in size of other nodes, liver, or spleen; splenic & hepatic nodules regressed by ≥ 50% in SPD; involvement of other organs usually assessable & no measurable disease present; no new sites of disease. Participants achieving CR, but with persistent morphologic bone marrow involvement or no bone marrow assessment after treatment were partial responders.
Up to 2 years (9 weeks of 3 21-day cycles and every 3 to 6 months during the long-term follow-up period)

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Kaplan-Meier Estimate of Progression Free Survival (PFS) 6 Months After Inotuzumab Ozogamicin Plus Rituximab Therapy
Tidsramme: 6 months after the first dose of inotuzumab ozogamicin
PFS; time from date of randomization to earliest date of progression, relapse after CR, death from any cause without progression, start of new treatment for the lymphoma excluding treatments/procedures for consolidation therapy in this protocol, or censored at date of last tumor assessment. Progression: abnormal lymph nodes (long axis > 1.5 cm or long axis 1.1 to 1.5 cm and short axis > 1.0 cm); appearance of any new lesion > 1.5 cm in any axis during or at end of treatment; ≥ 50% increase from nadir in SPD of any previously involved nodes, in a single involved node, or in the size of other lesions; ≥ 50% increase in longest diameter of any single previously identified node > 1.0 cm in short axis.
6 months after the first dose of inotuzumab ozogamicin
Kaplan-Meier Estimate of PFS 2 Years After Inotuzumab Ozogamicin Plus Rituximab Therapy
Tidsramme: 2 years after the first dose of inotuzumab ozogamicin
PFS; time from date of randomization to earliest date of progression, relapse after CR, death from any cause without progression, start of new treatment for the lymphoma excluding treatments/procedures for consolidation therapy in this protocol, or censored at date of last tumor assessment. Progression: abnormal lymph nodes (long axis > 1.5 cm or long axis 1.1 to 1.5 cm and short axis > 1.0 cm); appearance of any new lesion > 1.5 cm in any axis during or at end of treatment; ≥ 50% increase from nadir in SPD of any previously involved nodes, in a single involved node, or in the size of other lesions; ≥ 50% increase in longest diameter of any single previously identified node > 1.0 cm in short axis.
2 years after the first dose of inotuzumab ozogamicin
Percentage of Participants With a Response of CR or PR and Who Had Successful Granulocyte Colony Stimulating Factor (G-CSF) Mobilization of Peripheral Blood Stem Cells (PBSCs) Overall and After 3 Cycles of Inotuzumab Ozogamicin Plus Rituximab Therapy
Tidsramme: From the first dose to approximately 2 to 3 weeks after 3 cycles of inotuzumab ozogamicin plus rituximab (induction) therapy (up to 12 weeks) and up to approximately 2 to 3 weeks after 6 cycles (up to 21 weeks).
Successful mobilization of PBSC: ≥ 2 x 10^6 cluster of differentiation (CD) 34+ cells per kilogram (cells/kg) after 3 cycles. CR: no detectable clinical & radiographic evidence of disease/disease-related symptoms; lymph nodes/nodal masses regressed to normal size (≤ 1.5 cm in greatest transverse diameter for nodes > 1.5 cm pre-therapy); spleen & other organs (if enlarged pre-therapy) regressed in size & spleen not palpable on physical examination; repeat bone marrow infiltrate clear. PR: ≥ 50% decrease in SPD of 6 largest dominant nodes/nodal masses; no increase in size of other nodes, liver, or spleen; splenic & hepatic nodules regressed by ≥ 50% in SPD; involvement of other organs usually assessable & no measurable disease present; no new sites of disease. Participants achieving CR, but with persistent morphologic bone marrow involvement or no bone marrow assessment post treatment were partial responders. Response includes confirmed CR/PR and unconfirmed CR/PR.
From the first dose to approximately 2 to 3 weeks after 3 cycles of inotuzumab ozogamicin plus rituximab (induction) therapy (up to 12 weeks) and up to approximately 2 to 3 weeks after 6 cycles (up to 21 weeks).
Percentage of Participants With Successful G-CSF Mobilization of PBSC
Tidsramme: From the first dose to approximately 2 to 3 weeks after up to 6 cycles of inotuzumab ozogamicin plus rituximab (induction) therapy (up to 21 weeks).
Successful mobilization of PBSC was defined as ≥ 2 x 10^6 CD34+ cells/kg collected after 3 cycles of inotuzumab ozogamicin plus rituximab therapy.
From the first dose to approximately 2 to 3 weeks after up to 6 cycles of inotuzumab ozogamicin plus rituximab (induction) therapy (up to 21 weeks).
Percentage of Participants Who Underwent Autologous Stem Cell Transplant (aSCT)
Tidsramme: A minimum of 4 weeks and a maximum of 8 weeks after the last cycle of inotuzumab ozogamicin plus rituximab (induction) therapy (up to 26 weeks).
Participants underwent high dose chemotherapy and aSCT. In order to proceed to aSCT, participants were required to achieve CR or PR and successful collection of PSBC (≥ 2.0 x 10^6 CD34+ cells/kg collected after 3 cycles).
A minimum of 4 weeks and a maximum of 8 weeks after the last cycle of inotuzumab ozogamicin plus rituximab (induction) therapy (up to 26 weeks).
Event-Free Survival (EFS) After aSCT
Tidsramme: From the completion of aSCT through 2 year long-term follow-up period, including but not limited to planned assessments scheduled every 3 to 6 months.
EFS was the time (in months) from the date of aSCT to the earliest date of progression, relapse after CR, death from any cause without progression, initiation of a new treatment for the lymphoma or was censored at the date of the last tumor assessment.
From the completion of aSCT through 2 year long-term follow-up period, including but not limited to planned assessments scheduled every 3 to 6 months.
Percentage of Participants With a CR After 3 Cycles of Inotuzumab Ozogamicin Plus Rituximab Therapy
Tidsramme: From the first dose to approximately 2 to 3 weeks after 3 cycles of inotuzumab ozogamicin plus rituximab (induction) therapy (up to 12 weeks).
CR: complete disappearance of all detectable clinical & radiographic evidence of disease & disease-related symptoms; lymph nodes & nodal masses regressed to normal size (≤ 1.5 cm in their greatest transverse diameter for nodes > 1.5 cm before therapy); spleen and other organs (if enlarged prior to therapy) regressed in size & spleen not palpable on physical examination; repeat bone marrow infiltrate clear. Response includes confirmed CR and unconfirmed CR.
From the first dose to approximately 2 to 3 weeks after 3 cycles of inotuzumab ozogamicin plus rituximab (induction) therapy (up to 12 weeks).
Overall Survival (OS)
Tidsramme: From randomization until the date of death, or the date of last contact if no death occurred (up to 2 years).
OS was the time (in months) from the date of randomization to the date of death, and censored at the date of last contact if no death occurred.
From randomization until the date of death, or the date of last contact if no death occurred (up to 2 years).
Percentage of Participants With Any Grade 3/4 Laboratory Abnormality During Therapy
Tidsramme: Within 3 days prior each dose of test article, on Day -2, 1, 8, and 15 of Cycles 1 to 3, 2 to 3 weeks after Cycle 3, at the end-of-treatment visit, and every 3 to 6 months during long-term follow-up (up to 2 years).
The following parameters were analyzed for serum chemistry; blood urea nitrogen (or urea), creatinine, glucose, calcium, sodium, potassium, phosphorus, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, total bilirubin (and direct bilirubin, if total bilirubin was elevated), alkaline phosphatase, uric acid (or urate), albumin and total protein. The following parameters were analyzed for hematology; lymphocytes, basophils, eosinophils, erythrocytes, hematocrit, hemoglobin, leukocytes, monocytes, neutrophils, platelets, prothrombin international normalized ratio, prothrombin time, fibrinogen, and activated partial thromboplastin time. Laboratory test results were graded using the NCI Common Terminology Criteria for Adverse Events, version 3.0 (CTCAE v3.0).
Within 3 days prior each dose of test article, on Day -2, 1, 8, and 15 of Cycles 1 to 3, 2 to 3 weeks after Cycle 3, at the end-of-treatment visit, and every 3 to 6 months during long-term follow-up (up to 2 years).
Percentage of Participants With Treatment-Emergent Adverse Events (AEs) During Inotuzumab Ozogamicin Plus Rituximab Treatment
Tidsramme: Treatment emergent AEs were collected from time of first dose to end of trial visit (participants not undergoing consolidation treatment) or until consolidation therapy. SAEs were collected from informed consent until end of trial visit (up to 6 months).
An AE was any untoward, undesired, or unplanned event in the form of signs, symptoms, disease, or laboratory/physiologic observations occurring in a participant given a test article or in a clinical study; the event may not necessarily have had a causal relationship with the treatment. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; cancer. Treatment-emergent AEs were AEs that emerged after the first dose of the study treatment during the treatment period that were absent pre-treatment, or worsened during the treatment period relative to the pre-treatment state. The severity of all AEs was graded by the investigator using the NCI Common Terminology Criteria for AE Version 3.0 (CTCAE v3.0).
Treatment emergent AEs were collected from time of first dose to end of trial visit (participants not undergoing consolidation treatment) or until consolidation therapy. SAEs were collected from informed consent until end of trial visit (up to 6 months).

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Pfizer

Samarbejdspartnere

UCB Pharma

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Hjælpsomme links

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

8. juni 2009

Primær færdiggørelse (Faktiske)

31. oktober 2012

Studieafslutning (Faktiske)

31. oktober 2012

Datoer for studieregistrering

Først indsendt

20. marts 2009

Først indsendt, der opfyldte QC-kriterier

20. marts 2009

Først opslået (Skøn)

23. marts 2009

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

5. december 2017

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

30. oktober 2017

Sidst verificeret

1. oktober 2017

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • 3129K5-2005
  • B1931001 (Anden identifikator: Alias Study Number)
  • 2008-007802-12 (EudraCT nummer)

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

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