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

• ClinicalTrials.gov Identifier: NCT00867087
• Recruitment Status: Completed
• First Posted: March 23, 2009
• Results First Posted: August 22, 2017
• Last Update Posted: December 5, 2017
• Sponsor: Pfizer
• Collaborator: UCB Pharma
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: March 20, 2009
• First Posted Date: March 23, 2009
• Results First Submitted Date: July 24, 2017
• Results First Posted Date: August 22, 2017
• Last Update Posted Date: December 5, 2017
• Actual Study Start Date: June 8, 2009
• Actual Primary Completion Date: October 31, 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 24, 2017)

Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) After 3 Cycles of Inotuzumab Ozogamicin Plus Rituximab Therapy [ Time Frame: 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.

• Original Primary Outcome Measures (submitted: March 20, 2009): Overall response rate [ Time Frame: 6 months ]

Current Secondary Outcome Measures (submitted: July 24, 2017)

• Kaplan-Meier Estimate of Progression Free Survival (PFS) 6 Months After Inotuzumab Ozogamicin Plus Rituximab Therapy [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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).

• Original Secondary Outcome Measures (submitted: March 20, 2009): Pharmacokinetics: concentration of inotuzumab ozogamicin in serum [ Time Frame: 2-3 months ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study Evaluating Inotuzumab Ozogamicin (CMC-544) Plus Rituximab In Diffuse Large B-Cell Non-Hodgkin's Lymphoma
• Official Title: 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Lymphoma, B-Cell

Intervention

• Drug: inotuzumab ozogamicin (CMC-544)
  1.8 mg/m^2 every 21 days by intravenous infusion, 3 to 6 doses
  Other Name: cmc-544
• Drug: 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

Study Arms

Experimental: 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).

Interventions:

• Drug: inotuzumab ozogamicin (CMC-544)
• Drug: rituximab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 24, 2017): 64
• Original Estimated Enrollment (submitted: March 20, 2009): 60
• Actual Study Completion Date: October 31, 2012
• Actual Primary Completion Date: October 31, 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France, Germany, Korea, Republic of, Singapore, United Kingdom, United States
• Removed Location Countries: Hong Kong, Japan, Mexico, Poland

Administrative Information

• NCT Number: NCT00867087
• Other Study ID Numbers: 3129K5-2005; B1931001 ( Other Identifier: Alias Study Number ); 2008-007802-12 ( EudraCT Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Pfizer
• Study Sponsor: Pfizer
• Collaborators: UCB Pharma

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: October 2017