Study Evaluating Inotuzumab Ozogamicin (CMC-544) In Indolent Non-Hodgkins Lymphoma

Lymphoma Clinical Trial

Official title:

A Phase 2 Study Of Inotuzumab Ozogamicin (Cmc-544) In Subjects With Indolent Non-hodgkin's Lymphoma (Nhl) That Is Refractory To Or Has Relapsed After Rituximab And Chemotherapy Or Radioimmunotherapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00868608
• Other study ID #: 3129K7-2001
• Secondary ID: B19310072008-001
• Status: Completed
• Phase: Phase 2
• First received: March 24, 2009
• Last updated: October 27, 2017
• Start date: July 30, 2009
• Est. completion date: June 27, 2013

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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 81
• Est. completion date: June 27, 2013
• Est. primary completion date: January 10, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin

Intervention

Drug:
• Inotuzumab Ozogamicin (CMC-544)
Administered intravenously at 1.8 mg/m2 every 4 weeks for a planned 4 - 8 cycles

Locations

Country	Name	City	State
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	Universitaire Ziekenhuizen UZ Gasthuisberg	Leuven
Belgium	Oncologisch Centrum GZA - Location St. Augustinus	Wilrijk
Germany	Charite Berlin-Campus Virchow-Klinikum	Berlin
Germany	Charite Campus Mitte	Berlin
Hong Kong	The Chinese University of Hong Kong, Prince of Wales Hospital	Shatin, N.T.
Hungary	Debreceni Egyetem Orvos-es Egeszsegtudomanyi Centrum Belgyogyaszati Intezet,	Debrecen
Hungary	Kaposi Mor Oktato Korhaz, Belgyogyaszati Osztaly	Kaposvar
Japan	EPMint Co., Ltd	Aichi
Japan	Nagoya Daini Red Cross Hospital	Aichi
Japan	National Cancer Center Hospital	Chuo-ku	Tokyo
Japan	National Hospital Organization Kyushu Cancer Center	Fukuoka
Japan	National Hp. Org. Kyushu Medical Center	Fukuoka
Japan	Tokai University Hospital	Kanagawa
Japan	National Cancer Center Hospital East	Kashiwa	Chiba
Japan	Cancer Inst. Hp. of Japanese Foundation for Cancer Research	Tokyo
Korea, Republic of	Samsung Medical Center	Seoul	Korea
Netherlands	Erasmus MC Apotheek	Rotterdam
Netherlands	Erasmus Medisch Centrum	Rotterdam
Singapore	Singapore General Hospital	Singapore
United States	Quest Diagnostics	Allentown	Pennsylvania
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 Alabama Birmingham	Birmingham	Alabama
United States	Carlisle Regional Medical Center Lab	Carlisle	Pennsylvania
United States	Rush University Medical Center	Chicago	Illinois
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	John Theurer Cancer Center	Hackensack	New Jersey
United States	New York Medical College	Hawthorne	New York
United States	Penn State Milton S. Hershey medical Center	Hershey	Pennsylvania
United States	University of Texas, MD Anderson Cancer Center	Houston	Texas
United States	Lewistown Hospital	Lewistown	Pennsylvania
United States	Loma Linda University Cancer Center	Loma Linda	California
United States	Loma Linda University Cancer Center #5	Loma Linda	California
United States	Loma Linda University Medical Center	Loma Linda	California
United States	Facey Medical Group	Mission Hills	California
United States	Providence Holy Cross	Mission Hills	California
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Barnes-Jewish Hospital	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Park Nicollet Frauenshuh Cancer Center	Saint Louis Park	Minnesota
United States	CMSA Medical Lab	State College	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Pfizer	UCB Pharma

Countries where clinical trial is conducted

United States,  Belgium,  Germany,  Hong Kong,  Hungary,  Japan,  Korea, Republic of,  Netherlands,  Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Indolent NHL Achieving CR or Partial Response (PR) According to International Response Criteria for NHL	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.	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.
Secondary	Percentage of Participants With Follicular NHL Achieving CR or PR According to International Response Criteria for NHL	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.	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.
Secondary	Percentage of Participants With Indolent NHL Achieving a CR According to International Response Criteria for NHL	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.	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.
Secondary	Percentage of Participants With Follicular NHL Achieving a CR According to International Response Criteria for NHL	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.	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.
Secondary	Duration of Response in Participants With Indolent NHL	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.	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.
Secondary	Probability of Maintaining a Response at 6, 12 and 24 Months in Participants With Indolent NHL	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.	6, 12 and 24 months
Secondary	Duration of Response in Participants With Follicular NHL	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.	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.
Secondary	Probability of Maintaining a Response at 6, 12 and 24 Months in Participants With Follicular NHL	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.	6, 12 and 24 months
Secondary	Kaplan-Meier Estimate of the Progression-Free Survival (PFS) in Participants With Indolent NHL	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.	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.
Secondary	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	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.	6, 12 and 24 months
Secondary	Kaplan-Meier Estimate of the PFS in Participants With Follicular NHL	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.	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.
Secondary	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	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.	6, 12 and 24 months
Secondary	Kaplan-Meier Estimate of the Overall Survival (OS) in Participants With Indolent NHL	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.	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.
Secondary	Kaplan-Meier Estimates of the Probability of Survival at 6, 12 and 24 Months in Participants With Indolent NHL	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.	6, 12 and 24 months
Secondary	Kaplan-Meier Estimate of the OS in Participants With Follicular NHL	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.	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.
Secondary	Kaplan-Meier Esitmates of the Probability of Survival at 6, 12 and 24 Months in Participants With Follicular NHL	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.	6, 12 and 24 months
Secondary	Median Induced Change From Baseline of QT Study Specific Correction (QTcS) by Cycle Based on Median Maximum Calicheamicin Concentration (Cmax)	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	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
Secondary	Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population)	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.	Protocol reporting period: from informed consent to at least 28 days after the last dose.
Secondary	Percentage of Participants With QTc Interval Corrected Using Fridericia's Formula (QTcF) by Category (Safety Population)	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.	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.

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