Study Evaluating Inotuzumab Ozogamicin (CMC-544) In Indolent Non-Hodgkins Lymphoma
- Conditions
- Lymphoma
- Interventions
- Drug: Inotuzumab Ozogamicin (CMC-544)
- Registration Number
- NCT00868608
- Lead Sponsor
- Pfizer
- Brief Summary
The purpose of this study is to evaluate the efficacy of inotuzumab ozogamicin (CMC-544) in subjects with indolent Non-Hodgkins lymphoma (NHL) that is refractory or has relapsed after multiple therapies including rituximab or radioimmunotherapy. The investigational drug will be given to subjects with indolent NHL by intravenous infusion at a dose of 1.8 mg/m2, every 4 weeks.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 81
- Subjects who have been previously diagnosed with CD22-positive, indolent NHL (defined as follicular, marginal zone, or small lymphocytic lymphoma) that has progressed after 2 or more prior systemic therapies.
- Previous anticancer treatment given must have contained rituximab and chemotherapy, or anti CD20 Radio Immuno Therapy. Subjects must have exhibited no response or have progressed within 6 months from the completion of the most recent rituximab or rituximab containing therapy or within 12 months of the completion of Radio Immuno Therapy.
- Measurable disease with adequate bone marrow function, renal and hepatic function
- History of, or suggestive of, veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS) or history of chronic liver disease (eg, cirrhosis) or suspected alcohol abuse.
- Prior allogeneic hematopoietic stem cell transplant (HSCT).
- Clinical evidence of transformation to a more aggressive subtype of lymphoma or grade 3b follicular lymphoma.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description inotuzumab ozogamicin Inotuzumab Ozogamicin (CMC-544) inotuzumab ozogamicin
- Primary Outcome Measures
Name Time Method Percentage of Participants With Indolent NHL Achieving CR or Partial Response (PR) According to International Response Criteria for NHL Assessed for up to 2 years, including planned assessments every 8 to 12 weeks from first dose of study drug. Follow-up period may have been extended beyond 2 years due to dosing delays and allowed study visit windows. CR was defined as complete disappearance of all target lesions and disease-related symptoms; all nodes must have decreased to normal (less than or equal to \[≤\]1.5 cm in their greatest transverse diameter \[GTD\] for nodes more than \[\>\]1.5 cm before therapy) or ≤1 cm (short axis) in previously involved node; enlarged spleen prior to therapy must have regressed and be non-palpable; bone marrow lymphoma: infiltrate must have been cleared on repeat bone marrow aspirate and biopsy. PR was defined as \>50% decrease in the sum of the product diameters (SPD) of up to 6 index lesions. No increase in size of other nodes, liver or spleen. Splenic and hepatic nodules must have regressed by greater than or equal to \[≥\]50% in the SPD or GTD (for single nodules). With exception of splenic and hepatic nodules, involvement of other organs was usually assessable and no measurable disease should be present. No progression of non-target disease or new lesions.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Follicular NHL Achieving CR or PR According to International Response Criteria for NHL Assessed for up to 2 years, including planned assessments every 8 to 12 weeks from first dose of study drug. Follow-up period may have been extended beyond 2 years due to dosing delays and allowed study visit windows. CR was defined as complete disappearance of all target lesions and disease-related symptoms; all nodes must have decreased to normal (≤1.5 cm in their greatest transverse diameter for nodes \>1.5 cm before therapy) or ≤1 cm (short axis) in previously involved node; enlarged spleen prior to therapy must have regressed and be non-palpable; bone marrow lymphoma: infiltrate must have been cleared on repeat bone marrow aspirate and biopsy. PR was defined as \>50% decrease in the SPD of up to 6 index lesions. No increase in size of other nodes, liver or spleen. Splenic and hepatic nodules must have regressed by ≥50% in the SPD or greatest transverse diameter (for single nodules). With exception of splenic and hepatic nodules, involvement of other organs was usually assessable and no measurable disease should be present. No progression of non-target disease or new lesions.
Percentage of Participants With Indolent NHL Achieving a CR According to International Response Criteria for NHL Assessed for up to 2 years, including planned assessments every 8 to 12 weeks from first dose of study drug. Follow-up period may have been extended beyond 2 years due to dosing delays and allowed study visit windows. CR was defined as complete disappearance of all target lesions and disease-related symptoms; all nodes must have decreased to normal (≤1.5 cm in their greatest transverse diameter for nodes \>1.5 cm before therapy) or ≤1 cm (short axis) in previously involved node; enlarged spleen prior to therapy must have regressed and be non-palpable; bone marrow lymphoma: infiltrate must have been cleared on repeat bone marrow aspirate and biopsy.
Percentage of Participants With Follicular NHL Achieving a CR According to International Response Criteria for NHL Assessed for up to 2 years, including planned assessments every 8 to 12 weeks from first dose of study drug. Follow-up period may have been extended beyond 2 years due to dosing delays and allowed study visit windows. CR was defined as complete disappearance of all target lesions and disease-related symptoms; all nodes must have decreased to normal (≤1.5 cm in their greatest transverse diameter for nodes \>1.5 cm before therapy) or ≤1 cm (short axis) in previously involved node; enlarged spleen prior to therapy must have regressed and be non-palpable; bone marrow lymphoma: infiltrate must have been cleared on repeat bone marrow aspirate and biopsy.
Duration of Response in Participants With Indolent NHL Assessed for up to 2 years, including planned assessments every 8 to 12 weeks from first dose of study drug. Follow-up period may have been extended beyond 2 years due to dosing delays and allowed study visit windows. Duration of response was measured from the first date of response until the first date that the objective progression of disease (PD) or symptomatic deterioration or initiation of new anticancer therapy for the lymphoma or death from any cause is documented. Participants without an event were censored at the date of the last valid tumor assessment. A valid tumor assessment visit was defined as the tumor assessment visit with overall response of CR, PR, stable disease (SD), or PD, but not 'Not Done' or 'Unknown'. PD was defined according to the International Response Criteria for NHL: 1) New lesion or increase by ≥50% of previously involved sites from nadir, 2) New lesion(s) \>1.5 cm (any axis); ≥50% increase in SPD of \>1 node; or ≥50% increase in longest diameter of previously identified node \>1 cm in short axis, 3) \>50% increase from nadir in the SPD of any previous lesions (splenic or hepatic) and 4) New or recurrent involvement in bone marrow.
Probability of Maintaining a Response at 6, 12 and 24 Months in Participants With Indolent NHL 6, 12 and 24 months Duration of response was measured from the first date of response until the first date that the objective PD or symptomatic deterioration or initiation of new anticancer therapy for the lymphoma or death from any cause is documented. Participants without an event were censored at the date of the last valid tumor assessment. A valid tumor assessment visit was defined as the tumor assessment visit with overall response of CR, PR, stable disease (SD), or PD, but not 'Not Done' or 'Unknown'. PD was defined according to the International Response Criteria for NHL: 1) New lesion or increase by ≥50% of previously involved sites from nadir, 2) New lesion(s) \>1.5 cm (any axis); ≥50% increase in SPD of \>1 node; or ≥50% increase in longest diameter of previously identified node \>1 cm in short axis, 3) \>50% increase from nadir in the SPD of any previous lesions (splenic or hepatic) and 4) New or recurrent involvement in bone marrow.
Kaplan-Meier Esitmates of the Probability of Survival at 6, 12 and 24 Months in Participants With Follicular NHL 6, 12 and 24 months Kaplan-Meier: a rule for calculating an estimate of survival. OS was defined as the time from enrollment to death from any cause. For participants without death, censorship occurred at the date of last contact.
Duration of Response in Participants With Follicular NHL Assessed for up to 2 years, including planned assessments every 8 to 12 weeks from first dose of study drug. Follow-up period may have been extended beyond 2 years due to dosing delays and allowed study visit windows. Duration of response was measured from the first date of response until the first date that the objective PD or symptomatic deterioration or initiation of new anticancer therapy for the lymphoma or death from any cause is documented. Participants without an event were censored at the date of the last valid tumor assessment. A valid tumor assessment visit was defined as the tumor assessment visit with overall response of CR, PR, stable disease (SD), or PD, but not 'Not Done' or 'Unknown'. PD was defined according to the International Response Criteria for NHL: 1) New lesion or increase by ≥50% of previously involved sites from nadir, 2) New lesion(s) \>1.5 cm (any axis); ≥50% increase in SPD of \>1 node; or ≥50% increase in longest diameter of previously identified node \>1 cm in short axis, 3) \>50% increase from nadir in the SPD of any previous lesions (splenic or hepatic) and 4) New or recurrent involvement in bone marrow.
Probability of Maintaining a Response at 6, 12 and 24 Months in Participants With Follicular NHL 6, 12 and 24 months Duration of response was measured from the first date of response until the first date that the objective PD or symptomatic deterioration or initiation of new anticancer therapy for the lymphoma or death from any cause is documented. Participants without an event were censored at the date of the last valid tumor assessment. A valid tumor assessment visit was defined as the tumor assessment visit with overall response of CR, PR, stable disease (SD), or PD, but not 'Not Done' or 'Unknown'. PD was defined according to the International Response Criteria for NHL: 1) New lesion or increase by ≥50% of previously involved sites from nadir, 2) New lesion(s) \>1.5 cm (any axis); ≥50% increase in SPD of \>1 node; or ≥50% increase in longest diameter of previously identified node \>1 cm in short axis, 3) \>50% increase from nadir in the SPD of any previous lesions (splenic or hepatic) and 4) New or recurrent involvement in bone marrow.
Kaplan-Meier Estimate of the Progression-Free Survival (PFS) in Participants With Indolent NHL Assessed for up to 2 years, including planned assessments every 8 to 12 weeks from first dose of study drug. Follow-up period may have been extended beyond 2 years due to dosing delays and allowed study visit windows. Kaplan-Meier: a rule for calculating an estimate of survival. PFS was defined as time from enrollment to death from any cause without progression, progression during and after treatment, and initiation of all new anti-cancer treatments for the lymphoma. For participants with no event, censorship occurred at the date of last valid disease assessment. PD was defined in accordance with the International Response Criteria for NHL: 1) New lesion or increase by ≥50% of previously involved sites from nadir, 2) New lesion(s) \>1.5 cm (any axis); ≥50% increase in SPD of \>1 node; or ≥50% increase in longest diameter of previously identified node \>1 cm in short axis, 3) \>50% increase from nadir in the SPD of any previous lesions (splenic or hepatic) and 4) New or recurrent involvement in bone marrow.
Kaplan-Meier Estimates of the Probability of Being Alive and Free From PD or New Anticancer Therapy at 6, 12 and 24 Months in Participants With Indolent NHL 6, 12 and 24 months Kaplan-Meier: a rule for calculating an estimate of survival. PFS was defined as time from enrollment to death from any cause without progression, progression during and after treatment, and initiation of all new anti-cancer treatments for the lymphoma. For participants with no event, censorship occurred at the date of last valid disease assessment. PD was defined in accordance with the International Response Criteria for NHL: 1) New lesion or increase by ≥50% of previously involved sites from nadir, 2) New lesion(s) \>1.5 cm (any axis); ≥50% increase in SPD of \>1 node; or ≥50% increase in longest diameter of previously identified node \>1 cm in short axis, 3) \>50% increase from nadir in the SPD of any previous lesions (splenic or hepatic) and 4) New or recurrent involvement in bone marrow.
Kaplan-Meier Estimate of the PFS in Participants With Follicular NHL Assessed for up to 2 years, including planned assessments every 8 to 12 weeks from first dose of study drug. Follow-up period may have been extended beyond 2 years due to dosing delays and allowed study visit windows. Kaplan-Meier: a rule for calculating an estimate of survival. PFS was defined as time from enrollment to progression of disease or death from any cause. Events were defined as death from any cause without progression, progression during and after treatment, and initiation of all new anti-cancer treatments for the lymphoma. For participants with no event, censorship occurred at the date of last valid disease assessment. PD was defined in accordance with the International Response Criteria for NHL: 1) New lesion or increase by ≥50% of previously involved sites from nadir, 2) New lesion(s) \>1.5 cm (any axis); ≥50% increase in SPD of \>1 node; or ≥50% increase in longest diameter of previously identified node \>1 cm in short axis, 3) \>50% increase from nadir in the SPD of any previous lesions (splenic or hepatic) and 4) New or recurrent involvement in bone marrow.
Kaplan-Meier Estimate of the Probability of Being Alive and Free From PD or New Anticancer Therapy at 6, 12 and 24 Months in Participants With Follicular NHL 6, 12 and 24 months Kaplan-Meier: a rule for calculating an estimate of survival. PFS was defined as time from enrollment to progression of disease or death from any cause. Events were defined as death from any cause without progression, progression during and after treatment, and initiation of all new anti-cancer treatments for the lymphoma. For participants with no event, censorship occurred at the date of last valid disease assessment. PD was defined in accordance with the International Response Criteria for NHL: 1) New lesion or increase by ≥50% of previously involved sites from nadir, 2) New lesion(s) \>1.5 cm (any axis); ≥50% increase in SPD of \>1 node; or ≥50% increase in longest diameter of previously identified node \>1 cm in short axis, 3) \>50% increase from nadir in the SPD of any previous lesions (splenic or hepatic) and 4) New or recurrent involvement in bone marrow.
Kaplan-Meier Estimate of the Overall Survival (OS) in Participants With Indolent NHL Any time up to 2 years after enrollment. Follow-up period may have been extended beyond 2 years due to dosing delays and allowed study visit windows. Kaplan-Meier: a rule for calculating an estimate of survival. OS was defined as the time from enrollment to death from any cause. For participants without death, censorship occurred at the date of last contact.
Kaplan-Meier Estimates of the Probability of Survival at 6, 12 and 24 Months in Participants With Indolent NHL 6, 12 and 24 months Kaplan-Meier: a rule for calculating an estimate of survival. OS was defined as the time from enrollment to death from any cause. For participants without death, censorship occurred at the date of last contact.
Kaplan-Meier Estimate of the OS in Participants With Follicular NHL Any time up to 2 years after enrollment. Follow-up period may have been extended beyond 2 years due to dosing delays and allowed study visit windows. Kaplan-Meier: a rule for calculating an estimate of survival. OS was defined as the time from enrollment to death from any cause. For participants without death, censorship occurred at the date of last contact.
Median Induced Change From Baseline of QT Study Specific Correction (QTcS) by Cycle Based on Median Maximum Calicheamicin Concentration (Cmax) Cycle 1: pre-dose, 1 hour; Cycle 3 & 4: pre-dose, 1, 3, 48, 168 hours; Cycle 6 (if applicable): pre-dose; end of treatment: during clinic visit Triplicate 12-lead electrocardiogram (ECG) measurements were performed approximately 2 minutes apart. ECG assessments were pre-specified in the protocol to be time-matched with selected pharmacokinetic (PK) samples in order to conduct a concentration-QTc analysis. A study-specific QT correction factor was estimated using the un-averaged triplicate data and was used to calculate the study-specific corrected QT (QTcS). QTcS interval versus serum concentrations were modeled using a population analysis approach to identify potential effects of total calicheamicin exposure. Results for drug effects were based on the median Cmax for total calicheamicin across all participants: median Cmax was 61.3 ng/mL
Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) Protocol reporting period: from informed consent to at least 28 days after the last dose. Includes all TEAEs: any event that emerged after the first dose of the study treatment during the treatment period that was absent before administration of any study treatment, or worsened during the treatment period relative to the pre-treatment state.
Percentage of Participants With QTc Interval Corrected Using Fridericia's Formula (QTcF) by Category (Safety Population) Screening; Cycle 1: pre-dose & 1 hour; Cycles 3 and 4: pre-dose, 1, 3, 48, and 168 hours; Cycle 6: pre-dose; end of treatment: 28 to 56 days post-last dose. Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to the beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR). Maximum QTcF was categorized as less than or equal to (≤) 450 msec, \>450 msec to ≤480 msec, \>480 msec to ≤500 msec and \>500 msec. Participants are reported only once under the maximum QTcF interval observed at any of the time-points. Maximum increase from baseline was categorized as \<30 msec, ≥30 to \<60 msec (borderline) and ≥60 msec (prolonged) were summarized.
Trial Locations
- Locations (42)
New York Medical College
🇺🇸Hawthorne, New York, United States
University of Alabama Birmingham
🇺🇸Birmingham, Alabama, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
University of Alabama at Birmingham Comprehensive Cancer Center
🇺🇸Birmingham, Alabama, United States
University of Texas, MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Oncologisch Centrum GZA - Location St. Augustinus
🇧🇪Wilrijk, Belgium
Loma Linda University Cancer Center #5
🇺🇸Loma Linda, California, United States
Loma Linda University Cancer Center
🇺🇸Loma Linda, California, United States
Facey Medical Group
🇺🇸Mission Hills, California, United States
Providence Holy Cross
🇺🇸Mission Hills, California, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Barnes-Jewish Hospital
🇺🇸Saint Louis, Missouri, United States
Park Nicollet Frauenshuh Cancer Center
🇺🇸Saint Louis Park, Minnesota, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Quest Diagnostics
🇺🇸Allentown, Pennsylvania, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Carlisle Regional Medical Center Lab
🇺🇸Carlisle, Pennsylvania, United States
Penn State Milton S. Hershey medical Center
🇺🇸Hershey, Pennsylvania, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Lewistown Hospital
🇺🇸Lewistown, Pennsylvania, United States
Universitair Ziekenhuis Gent
🇧🇪Gent, Belgium
CMSA Medical Lab
🇺🇸State College, Pennsylvania, United States
Charite Campus Mitte
🇩🇪Berlin, Germany
Universitaire Ziekenhuizen UZ Gasthuisberg
🇧🇪Leuven, Belgium
Charite Berlin-Campus Virchow-Klinikum
🇩🇪Berlin, Germany
Debreceni Egyetem Orvos-es Egeszsegtudomanyi Centrum Belgyogyaszati Intezet,
🇭🇺Debrecen, Hungary
Kaposi Mor Oktato Korhaz, Belgyogyaszati Osztaly
🇭🇺Kaposvar, Hungary
National Cancer Center Hospital
🇯🇵Chuo-ku, Tokyo, Japan
EPMint Co., Ltd
🇯🇵Aichi, Japan
National Cancer Center Hospital East
🇯🇵Kashiwa, Chiba, Japan
Nagoya Daini Red Cross Hospital
🇯🇵Aichi, Japan
Tokai University Hospital
🇯🇵Kanagawa, Japan
National Hospital Organization Kyushu Cancer Center
🇯🇵Fukuoka, Japan
National Hp. Org. Kyushu Medical Center
🇯🇵Fukuoka, Japan
Cancer Inst. Hp. of Japanese Foundation for Cancer Research
🇯🇵Tokyo, Japan
Samsung Medical Center
🇰🇷Seoul, Korea, Korea, Republic of
Erasmus Medisch Centrum
🇳🇱Rotterdam, Netherlands
Erasmus MC Apotheek
🇳🇱Rotterdam, Netherlands
Singapore General Hospital
🇸🇬Singapore, Singapore
Loma Linda University Medical Center
🇺🇸Loma Linda, California, United States
John Theurer Cancer Center
🇺🇸Hackensack, New Jersey, United States
The Chinese University of Hong Kong, Prince of Wales Hospital
🇭🇰Shatin, N.T., Hong Kong