Clinical trial NCT01055496: Study Evaluating Chemotherapy in Combination With Inotuzumab Ozogamicin In Subjects With Non-Hodgkin's Lymphoma
Official title: AN OPEN-LABEL, PHASE 1 STUDY OF R-CVP OR R-GDP IN COMBINATION WITH INOTUZUMAB OZOGAMICIN IN SUBJECTS WITH CD22-POSTIVE NON-HODGKIN'S LYMPHOMA
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lymphoma, B-Cell
Keywords: Non-Hodgkin's lymphoma
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: UCB Pharma
First posted: 2010-01-25
Enrollment: 103
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Primary purpose: TREATMENT

Brief summary: This is a phase 1 trial designed to evaluate safety and tolerability of chemotherapy in combination with inotuzumab ozogamicin, an investigational product, in adults with CD22-positive non-Hodgkin's lymphoma. The trial will involve two arms. In one arm, subjects will receive chemotherapy regimen R-CVP (rituximab, cyclophosphamide, vincristine and prednisone). In the other arm, subjects will receive R-GDP (rituximab, gemcitabine, cisplatinum and dexamethasone). Subjects in both arms will also receive inotuzumab ozogamicin.


Eligibility criteria: Inclusion Criteria:

* Dose escalation cohorts: subjects with diagnosis of CD22-positive Non-Hodgkin's Lymphoma (NHL) who have had at least 1 prior anticancer treatment, including prior treatment with rituximab and chemotherapy.
* Expanded maximum tolerated dose (MTD) confirmation and preliminary efficacy cohorts: subjects with diagnosis of CD22-positive NHL who have had at least 1 prior anticancer treatment, including prior treatment with rituximab and chemotherapy or newly diagnosed subjects who are not candidates for anthracycline-based therapy.
* At least 1 measurable disease lesion that is \> 1 cm in the longest transverse diameter, with a product of the diameters \> 2.25 cm2 by CT or magnetic resonance imaging (MRI).

Exclusion Criteria:

* Candidate for potentially curative therapy such as stem cell transplantation.
* Prior allogeneic hematopoietic stem cell transplantation (HSCT).
* Prior autologous transplantation, radioimmunotherapy, or other anti CD22 immunotherapy \<= 6 months before the first dose of investigational product.
* More than 3 previous combination chemotherapy (2 or more cytotoxics) anticancer regimens.

Primary outcomes:
measure: Participants Reporting Dose Limiting Toxicity (DLT) Adverse Events (AEs) for Participants in the DE Cohort and the MTD Confirmation Cohort for Arm 1
timeFrame: From the first dose of study medication (Study Day 1) to the completion of the first 21-day cycle.
measure: Participants Reporting DLT AEs for Participants in the DE Cohort and the MTD Confirmation Cohort for Arm 2
timeFrame: From the first dose of study medication (Study Day 1) to the completion of the first 21-day cycle.
measure: Percentage of Participants With Best Overall Response (OR) of Complete Response (CR) or Partial Response (PR) According to International Response Criteria for NHLs in the MTD and EE Cohorts
timeFrame: From first dose of study medication through 2 year follow-up period, including but not limited to planned assessments scheduled every 9 to 24 weeks.
measure: Percentage of Participants With a Treatment Emergent AE
timeFrame: SAEs were assessed from informed consent through and including the end of treatment visit (at least 28 calendar days after last study drug administration). Non-SAEs were recorded from time of the first dose of study drug through last participant visit.
measure: Percentage of Participants With Any Grade 3/4 Chemistry Abnormality During Therapy
timeFrame: Within 3 days prior to the start of each cycle, on Day 8 of each cycle, on Day 15 of Cycles 1, 2, and 3, and the end-of-treatment visit. Each Cycle is 21 Days.
measure: Percentage of Participants With Any Grade 3/4 Hematology Abnormality During Therapy
timeFrame: Within 3 days prior to the start of each cycle, Day 8 of each cycle, Day 15 of Cycles 1, 2, and 3, and the end-of-treatment visit. Each Cycle is 21 Days.
Secondary outcomes:
measure: Percentage of Participants With a Best OR of CR or PR According to International Response Criteria for NHLs in the DE Cohorts
timeFrame: From first dose of study medication through 2 year follow-up period, including but not limited to planned assessments scheduled every 9 to 24 weeks.
measure: Kaplan-Meier Estimate of the Progression-Free Survival (PFS) in the DE Cohorts
timeFrame: From first dose of study medication through 2 year follow-up period, including but not limited to planned assessments scheduled every 9 to 24 weeks
measure: Kaplan-Meier Estimates of the Probability of Being Alive and Free From PD or New Anticancer Therapy at 6, 12, and 24 Months in the DE Cohorts
timeFrame: 6, 12 and 24 months
measure: Kaplan-Meier Estimate of the PFS in the MTD Confirmation/EE Cohorts
timeFrame: From first dose of study medication through 2 year follow-up period, including but not limited to planned assessments scheduled every 9 to 24 weeks
measure: Kaplan-Meier Estimates of the Probability of Being Alive and Free From PD or New Anticancer Therapy at 6, 12, and 24 Months in the MTD Confirmation/EE Cohorts.
timeFrame: 6, 12, and 24 months
measure: Kaplan-Meier Estimate of the Overall Survival (OS) in the DE Cohorts
timeFrame: From first dose of study medication through 2 year follow-up period
measure: Kaplan-Meier Estimates of the Probability of Being Alive at 6, 12, and 24 Months in the DE Cohorts
timeFrame: 6, 12, and 24 months
measure: Kaplan-Meier Estimate of the OS in the MTD Confirmation/EE Cohorts
timeFrame: From first dose of study medication through 2 year follow-up period
measure: Kaplan-Meier Estimates of the Probability of Being Alive at 6, 12, and 24 Months in the MTD Confirmation/EE Cohorts
timeFrame: 6, 12, and 24 Months
measure: Mean Inotuzumab Ozogamicin Serum Concentrations
timeFrame: Pre-dose on Cycle 1, Day 2; Pre-dose, 1 and 3 hours post-dose on Cycle 3, Day 2; 24 hours post-dose on Cycle 3, Day 3 and 168 hours post-dose on Cycle 3, Day 8.
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: Davis Cancer Pavillion and Shands Medical Plaza
state: Florida
city: Gainesville
country: United States
facility: Shands Cancer Hospital At The University Of Florida
state: Florida
city: Gainesville
country: United States
facility: Shands Hospital at the University of Florida
state: Florida
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Federal Way
country: United States
facility: Northwest Medical Specialties, PLLC
state: Washington
city: Gig Harbor
country: United States
facility: Northwest Medical Specialties, PLLC
state: Washington
city: Lakewood
country: United States
facility: Northwest Medical Specialties, PLLC
state: Washington
city: Puyallup
country: United States
facility: Rainier Physicians, PC
state: Washington
city: Tacoma
country: United States
facility: Northwest Medical Specialties PLLC
state: Washington
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: UZ Gasthuisberg
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Halifax
country: Canada
facility: Queen Elizabeth Health Sciences Centre
state: Nova Scotia
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Paris Cedex 10
country: France
facility: Hospital Saint-Louis - Service d'Hemato-Oncologie
city: Paris
country: France
facility: Hopital Saint-Louis -Universite Paris VII
city: Pierre Benite
country: France
facility: Centre Hospitalier Lyon Sud - Service d'Hematologie
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital
city: Nagoya
country: Japan
facility: Nagoya Daini Red Cross Hospital
state: Aichi
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Koto-Ku
country: Japan
facility: Cancer Institute Hospital, Japanese Foundation For Cancer Research
state: Tokyo
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Singapore
country: Singapore
facility: Singapore General Hospital
city: Eastleigh
country: United Kingdom
facility: Nuffield Hospital
state: Hants
city: Southampton
country: United Kingdom
facility: Spire Southampton Hospital
state: Hants
city: Southampton
country: United Kingdom
facility: Cancer Sciences Division, Somers Cancer Research Building
state: Hants
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Foundation Trust
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Sangha R, Davies A, Dang NH, Ogura M, MacDonald DA, Ananthakrishnan R, Paccagnella ML, Vandendries E, Boni J, Goh YT. Phase 1 study of inotuzumab ozogamicin combined with R-GDP for the treatment of patients with relapsed/refractory CD22+ B-cell non-Hodgkin lymphoma. J Drug Assess. 2017 Aug 16;6(1):10-17. doi: 10.1080/21556660.2017.1315336. eCollection 2017.
citation: Ogura M, Tobinai K, Hatake K, Davies A, Crump M, Ananthakrishnan R, Ishibashi T, Paccagnella ML, Boni J, Vandendries E, MacDonald D. Phase I Study of Inotuzumab Ozogamicin Combined with R-CVP for Relapsed/Refractory CD22+ B-cell Non-Hodgkin Lymphoma. Clin Cancer Res. 2016 Oct 1;22(19):4807-4816. doi: 10.1158/1078-0432.CCR-15-2488. Epub 2016 May 6.