Study Evaluating Chemotherapy in Combination With Inotuzumab Ozogamicin In Subjects With Non-Hodgkin's Lymphoma
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
3 other identifiers
interventional
103
9 countries
28
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Mar 2010
Longer than P75 for phase_1
28 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 21, 2010
CompletedFirst Posted
Study publicly available on registry
January 25, 2010
CompletedStudy Start
First participant enrolled
March 1, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2014
CompletedResults Posted
Study results publicly available
August 2, 2019
CompletedAugust 2, 2019
June 1, 2019
3.3 years
January 21, 2010
July 24, 2017
June 13, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (6)
Participants Reporting Dose Limiting Toxicity (DLT) Adverse Events (AEs) for Participants in the DE Cohort and the MTD Confirmation Cohort for Arm 1
DLT was defined as: febrile neutropenia, Grade (Gr) 4 neutropenia ≥7 days, Gr 4 thrombocytopenia ≥7 days, Gr 3/4 thrombocytopenia associated with bleeding requiring a transfusion, Gr 3/4 non-hematologic toxicity (except alopecia) ≥7 days or treatment-related and clinically significant irrespective of duration, ≥Gr 3 QTc prolongation, Gr 4 alanine or aspartate aminotransferase, Gr 2 hyperbilirubinemia (greater than (\>)1.5 x upper normal limit) \>7 days, delayed recovery from a treatment-related toxicity that prevented re-dosing by \>7 days, or Granulocyte-colony stimulating factor treatment during the first cycle.
From the first dose of study medication (Study Day 1) to the completion of the first 21-day cycle.
Participants Reporting DLT AEs for Participants in the DE Cohort and the MTD Confirmation Cohort for Arm 2
DLT was defined as: febrile neutropenia, Grade (Gr) 4 neutropenia ≥7 days, Gr 4 thrombocytopenia ≥7 days, Gr 3/4 thrombocytopenia associated with bleeding requiring a transfusion, Gr 3/4 non-hematologic toxicity (except alopecia) ≥7 days or treatment-related and clinically significant irrespective of duration, ≥Gr 3 QTc prolongation, Gr 4 alanine or aspartate aminotransferase, Gr 2 hyperbilirubinemia (greater than (\>)1.5 x upper normal limit) \>7 days, delayed recovery from a treatment-related toxicity that prevented re-dosing by \>7 days, or Granulocyte-colony stimulating factor treatment during the first cycle.
From the first dose of study medication (Study Day 1) to the completion of the first 21-day cycle.
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
OR was evaluated according to the International Response Criteria for NHLs. CR was defined as complete disappearance of all lesions and disease-related symptoms; all nodes must have decreased to normal (less than or equal to \[≤\]1.5 centimeters \[cm\] in their greatest transverse diameter (GTD) 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 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 ≥50% in the SPD or GTD (for single nodules). With the exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present. No progression of non-target disease or new lesions.
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.
Percentage of Participants With a Treatment Emergent AE
An AE was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event may not necessarily have had a causal relationship with the treatment or usage. 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. Treatment-emergent AEs were defined as those occurring on or after the first study drug dose day through and including 56 days post last dose of study drug. The severity of all AEs was graded by the investigator using the National Cancer Institute Common Terminology Criteria for AE Version 3.0 (NCI CTCAE v3.0).
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.
Percentage of Participants With Any Grade 3/4 Chemistry Abnormality During Therapy
The following parameters were analyzed for blood 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. Laboratory test results were graded using the NCI CTCAE v3.0 where CTCAE Grade 3 equals "severe" and CTCAE Grade 4 equals "life threatening or disabling."
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.
Percentage of Participants With Any Grade 3/4 Hematology Abnormality During Therapy
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 CTCAE v3.0 where CTCAE Grade 3 equals "severe" and CTCAE Grade 4 equals "life threatening or disabling."
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 (10)
Percentage of Participants With a Best OR of CR or PR According to International Response Criteria for NHLs in the DE Cohorts
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.
Kaplan-Meier Estimate of the Progression-Free Survival (PFS) in the DE Cohorts
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
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
6, 12 and 24 months
Kaplan-Meier Estimate of the PFS in the MTD Confirmation/EE Cohorts
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
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.
6, 12, and 24 months
- +5 more secondary outcomes
Study Arms (2)
Arm 1 (R-CVP)
EXPERIMENTALSubjects in arm 1 will be enrolled in dose escalation cohorts that will initially evaluate an escalating dose of cyclophosphamide in combination with set doses of inotuzumab ozogamicin, vincristine, prednisone, and rituximab.
Arm 2 (R-GDP)
EXPERIMENTALSubjects in arm 2 will be enrolled in dose escalation cohorts that will initially evaluate escalating doses of gemcitabine and/or cisplatinum in combination with set doses of inotuzumab ozogamicin, dexamethasone, and rituximab.
Interventions
Day 1: Rituximab at 375 mg/m2 Cyclophosphamide at 375 mg/m2 (cohort 1), 550mg/m2 (cohort 2), 750 mg/m2 (cohort 3, 4) Vincristine at 1.4 mg/m2 (max 2 mg) Day 2 Inotuzumab ozogamicin at 0.8 mg/m2 (cohort 1, 2, 3), 1.3 mg/m2 (cohort 4) Days 1-5: Prednisone at 40 mg/m2 Each cycle is 3 weeks, with a maximum of 6 cycles total.
Day 1: Rituximab at 375 mg/m2 Gemcitabine at 500 mg/m2 (cohort 1, 2b, 3b), 1000mg/m2 (cohort 2a, 3a, 4, 5) Cisplatin at 37.5 mg/m2 (cohort 1, 2a), 50mg/m2 (cohort 2b, 3a), 75mg/m2 (cohort 3b, 4, 5) Day 2: Inotuzumab ozogamicin at 0.8 mg/m2 (cohort 1, 2a, 2b, 3a, 3b, 4), 1.3mg/m2 (cohort 5) Days 1-4: Dexamethasone at 40 mg Each cycle is 3 weeks, with a maximum of 6 cycles total.
Eligibility Criteria
You may qualify if:
- 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).
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Pfizerlead
- UCB Pharmacollaborator
Study Sites (28)
Davis Cancer Pavillion and Shands Medical Plaza
Gainesville, Florida, 32608, United States
Shands Cancer Hospital At The University Of Florida
Gainesville, Florida, 32608, United States
Shands Hospital at the University of Florida
Gainesville, Florida, 32610, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111-2497, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030-4009, United States
Northwest Medical Specialties, PLLC
Federal Way, Washington, 98003, United States
Northwest Medical Specialties, PLLC
Gig Harbor, Washington, 98332, United States
Northwest Medical Specialties, PLLC
Lakewood, Washington, 98499, United States
Rainier Physicians, PC
Puyallup, Washington, 98373, United States
Northwest Medical Specialties PLLC
Tacoma, Washington, 98405, United States
UZ Gent
Ghent, 9000, Belgium
UZ Gasthuisberg
Leuven, 3000, Belgium
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2, Canada
Queen Elizabeth Health Sciences Centre
Halifax, Nova Scotia, B3H 2Y9, Canada
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2M9, Canada
Hopital Saint-Louis -Universite Paris VII
Paris, 75010, France
Hospital Saint-Louis - Service d'Hemato-Oncologie
Paris, 75475, France
Centre Hospitalier Lyon Sud - Service d'Hematologie
Pierre-Bénite, 69495, France
Prince of Wales Hospital
Hong Kong, Hong Kong
Nagoya Daini Red Cross Hospital
Nagoya, Aichi-ken, 466-8650, Japan
National Cancer Center Hospital
Chuo-ku, Tokyo, 104-0045, Japan
Cancer Institute Hospital, Japanese Foundation For Cancer Research
Koto-Ku, Tokyo, 135-8550, Japan
Singapore General Hospital
Singapore, 169608, Singapore
Samsung Medical Center
Seoul, 135-710, South Korea
Nuffield Hospital
Eastleigh, Hants, SO53 2DW, United Kingdom
Spire Southampton Hospital
Southampton, Hants, SO16 6UY, United Kingdom
Cancer Sciences Division, Somers Cancer Research Building
Southampton, Hants, SO16 6YD, United Kingdom
Guy's and St Thomas' NHS Foundation Trust
London, SE1 9RT, United Kingdom
Related Publications (2)
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.
PMID: 28959500DERIVEDOgura 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.
PMID: 27154915DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
This is a preliminary study with a limited number of participants, which was performed primarily to assess safety.The sample size for this study was determined by clinical rather than statistical considerations.
Results Point of Contact
- Title
- Pfizer ClinicalTrials.gov Call Center
- Organization
- Pfizer, Inc.
Study Officials
- STUDY DIRECTOR
Pfizer CT.gov Call Center
Pfizer
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- GT60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 21, 2010
First Posted
January 25, 2010
Study Start
March 1, 2010
Primary Completion
July 1, 2013
Study Completion
March 1, 2014
Last Updated
August 2, 2019
Results First Posted
August 2, 2019
Record last verified: 2019-06
Data Sharing
- IPD Sharing
- Will not share
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.