Study Evaluating Inotuzumab Ozogamicin (CMC-544) Plus Rituximab In Diffuse Large B-Cell Non-Hodgkin's Lymphoma
- Conditions
- Lymphoma, B-Cell
- Interventions
- Drug: inotuzumab ozogamicin (CMC-544)Drug: rituximab
- Registration Number
- NCT00867087
- Lead Sponsor
- Pfizer
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 64
- 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)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Rituximab 375 mg/m^2 + Inotuzumab Ozogamicin 1.8 mg/m^2 inotuzumab ozogamicin (CMC-544) 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). Rituximab 375 mg/m^2 + Inotuzumab Ozogamicin 1.8 mg/m^2 rituximab 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).
- Primary Outcome Measures
Name Time Method Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) After 3 Cycles of Inotuzumab Ozogamicin Plus Rituximab Therapy 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.
- Secondary Outcome Measures
Name Time Method Kaplan-Meier Estimate of Progression Free Survival (PFS) 6 Months After Inotuzumab Ozogamicin Plus Rituximab Therapy 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.
Kaplan-Meier Estimate of PFS 2 Years After Inotuzumab Ozogamicin Plus Rituximab Therapy 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.
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 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.
Percentage of Participants With Successful G-CSF Mobilization of PBSC 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.
Percentage of Participants Who Underwent Autologous Stem Cell Transplant (aSCT) 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).
Event-Free Survival (EFS) After aSCT 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.
Percentage of Participants With a CR After 3 Cycles of Inotuzumab Ozogamicin Plus Rituximab Therapy 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.
Overall Survival (OS) 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.
Percentage of Participants With Any Grade 3/4 Laboratory Abnormality During Therapy 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).
Percentage of Participants With Treatment-Emergent Adverse Events (AEs) During Inotuzumab Ozogamicin Plus Rituximab Treatment 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).
Trial Locations
- Locations (33)
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
University of Texas, MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
CHU Saint-Eloi
🇫🇷Montpellier Cedex 5, France
Hopital Saint Louis
🇫🇷Paris, France
Loyola University Medical Center, Foster G. McGraw Hospital and Satellites
🇺🇸Maywood, Illinois, United States
Barnes-Jewish Hospital
🇺🇸Saint Louis, Missouri, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Siteman Cancer Center
🇺🇸Saint Peters, Missouri, United States
Hackensack University Medical CenteR
🇺🇸Hackensack, New Jersey, United States
Memorial Sloan - Kettering Cancer Center
🇺🇸New York, New York, United States
Penn State Milton S Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
UT Southwestern University Hospital - St. Paul
🇺🇸Dallas, Texas, United States
Zale Lipshy University Hospital
🇺🇸Dallas, Texas, United States
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
The University of Texas, M. D. Anderson Cancer Center
🇺🇸Houston, Texas, United States
University of Wisconsin Hospital and Clinics
🇺🇸Madison, Wisconsin, United States
CHRU de Lille Hopital Claude Huriez
🇫🇷Lille, France
Pharmaceutical Research Center
🇺🇸Madison, Wisconsin, United States
Institut Paoli Calmettes
🇫🇷Marseille, France
Hopital Haut-Leveque
🇫🇷Pessac, France
CH Lyon Sud
🇫🇷Pierre-benite Cedex, France
Departement d'Hematologie et d'Oncologie-
🇫🇷Strasbourg, France
Charite Campus Virchow-Kilinikum-
🇩🇪Berlin, Germany
Samsung Medical Center
🇰🇷Seoul, Gangnam-gu, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Seoul/korea, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Singapore General Hospital
🇸🇬Singapore, Singapore
Christie Hospital
🇬🇧Manchester, United Kingdom
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
John Theurer Cancer Center (JTCC) at Hackensack University Medical Center (HUMC)
🇺🇸Hackensack, New Jersey, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Methodist Healthcare System of
🇺🇸San Antonio, Texas, United States
John Theurer Cancer Center, Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States