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

Lymphoma, B-Cell Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00867087
• Other study ID #: 3129K5-2005
• Secondary ID: B19310012008-007
• Status: Completed
• Phase: Phase 2
• First received: March 20, 2009
• Last updated: October 30, 2017
• Start date: June 8, 2009
• Est. completion date: October 31, 2012

Study information

• Verified date: October 2017
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: October 31, 2012
• Est. primary completion date: October 31, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

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

Locations

Country	Name	City	State
France	CHRU de Lille Hopital Claude Huriez	Lille
France	Institut Paoli Calmettes	Marseille
France	CHU Saint-Eloi	Montpellier Cedex 5
France	Hopital Saint Louis	Paris
France	Hopital Haut-Leveque	Pessac
France	CH Lyon Sud	Pierre-benite Cedex
France	CH Lyon Sud	Pierre-Benite cedex 114
France	Departement d'Hematologie et d'Oncologie-	Strasbourg
Germany	Charite Campus Virchow-Kilinikum-	Berlin
Korea, Republic of	Asan Medical Center	Seoul	Seoul/korea
Korea, Republic of	Samsung Medical Center	Seoul	Gangnam-gu
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Singapore	Singapore General Hospital	Singapore
United Kingdom	Christie Hospital	Manchester
United Kingdom	The Christie NHS Foundation Trust	Manchester
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Tufts Medical Center	Boston	Massachusetts
United States	UT Southwestern Medical Center	Dallas	Texas
United States	UT Southwestern University Hospital - St. Paul	Dallas	Texas
United States	Zale Lipshy University Hospital	Dallas	Texas
United States	Hackensack University Medical CenteR	Hackensack	New Jersey
United States	John Theurer Cancer Center (JTCC) at Hackensack University Medical Center (HUMC)	Hackensack	New Jersey
United States	John Theurer Cancer Center (JTCC) at Hackensack University Medical Center (HUMC)	Hackensack	New Jersey
United States	John Theurer Cancer Center (JTCC) at Hackensack University Medical Center (HUMC)	Hackensack	New Jersey
United States	John Theurer Cancer Center, Hackensack University Medical Center	Hackensack	New Jersey
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	The University of Texas, M. D. Anderson Cancer Center	Houston	Texas
United States	University of Texas, MD Anderson Cancer Center	Houston	Texas
United States	Pharmaceutical Research Center	Madison	Wisconsin
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	Loyola University Medical Center, Foster G. McGraw Hospital and Satellites	Maywood	Illinois
United States	Memorial Sloan - Kettering Cancer Center	New York	New York
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	Methodist Healthcare System of	San Antonio	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Pfizer	UCB Pharma

Countries where clinical trial is conducted

United States,  France,  Germany,  Korea, Republic of,  Singapore,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) After 3 Cycles of Inotuzumab Ozogamicin Plus Rituximab Therapy	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)
Secondary	Kaplan-Meier Estimate of Progression Free Survival (PFS) 6 Months After Inotuzumab Ozogamicin Plus Rituximab Therapy	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
Secondary	Kaplan-Meier Estimate of PFS 2 Years After Inotuzumab Ozogamicin Plus Rituximab Therapy	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
Secondary	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	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).
Secondary	Percentage of Participants With Successful G-CSF Mobilization of PBSC	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).
Secondary	Percentage of Participants Who Underwent Autologous Stem Cell Transplant (aSCT)	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).
Secondary	Event-Free Survival (EFS) After aSCT	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.
Secondary	Percentage of Participants With a CR After 3 Cycles of Inotuzumab Ozogamicin Plus Rituximab Therapy	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).
Secondary	Overall Survival (OS)	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).
Secondary	Percentage of Participants With Any Grade 3/4 Laboratory Abnormality During Therapy	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).
Secondary	Percentage of Participants With Treatment-Emergent Adverse Events (AEs) During Inotuzumab Ozogamicin Plus Rituximab Treatment	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).

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