Lymphoma, FollicularPhase 3NCT00562965
Study Comparing Inotuzumab Ozogamicin In Combination With Rituximab Versus Defined Investigator's Choice In Follicular Non-Hodgkin's Lymphoma (NHL)
A Phase 3 study testing inotuzumab ozogamicin, rituximab and cyclophosphamide in people with Lymphoma, Follicular, run by Pfizer at 39 sites in 14 countries.
Trial summary
This protocol is designed to assess the efficacy and safety of inotuzumab ozogamicin given with rituximab compared to a defined investigator's choice therapy. Subjects will be randomized to one of these two arms of the study. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma, Follicular
- What is being tested?
- inotuzumab ozogamicin, rituximab and cyclophosphamide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 39 sitesin 14 countries
- Study dates
- Nov 2007to Apr 2011
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects with a diagnosis of CD20 and CD22-positive, follicular lymphoma, who have received 1 or 2 prior regimens, at least 1 of which should have contained administration of rituximab (either as a single agent or in combination).
- Age 18 years or older.
- ECOG performance status <= 2.
- ANC >= 1.5 x 10^9/L (1500/mL) and platelets >= 75 x 10^9/L (75,000/mL), serum creatinine <= 1.5 x ULN and urine protein to creatinine ratio of <= 0.5, total bilirubin <= 1.5 x ULN, AST and ALT <= 2.5 x ULN.
- At least 1 measurable disease lesion that is >= 1.5 cm x 1.5 cm by CT or MRI, in an area of no prior radiation therapy, or documented progression in an area that was previously irradiated.
Who cannot join
- Subjects with clinical evidence of transformation to a more aggressive subtype of lymphoma or grade 3b follicular lymphoma.
- Subjects whose disease is rituximab refractory, meaning that they did not have a CR or PR, or that they experienced disease progression within 6 months from the initiation of the rituximab or rituximab containing treatment regimen administered immediately preceding study enrollment.
Trial locations and contacts
39 sites in 14 countries.
39 sites in 14 countries
United States17 sites
Advanced Oncology Associates
Armonk, New York, 10504
The Harry & Jeanette Weinberg Cancer Inst at Franklin Square
Baltimore, Maryland, 21237
Hematology and Oncology Associates
Columbus, Mississippi, 39706
Hematology and Oncology Associates
Corinth, Mississippi, 38834
Deaconess Clinic
Evansville, Indiana, 47713
Hackensack University Medical Center
Hackensack, New Jersey, 07601
The Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, 07601
Facey Medical Group
Mission Hills, California, 91345
Hematology Oncology Associates of Northern New Jersy
Morristown, New Jersey, 07960
Advanced Oncology Associates
New Rochelle, New York, 10801
Newland Medical Associates
Novi, Michigan, 48374
Marc Zimmerman, MD
Pomona, New York, 10970
Park Nicollet Frauenshuh Cancer Center
Saint Louis Park, Minnesota, 55426
Newland Medical Associates, PC
Southfield, Michigan, 48075
Avi Einzing, MD
The Bronx, New York, 10461
Hematology and Oncology Associates at Bridgepoint
Tupelo, Mississippi, 38801
Wenatchee Valley Medical Center
Wenatchee, Washington, 98801
Canada4 sites
Hopital Charles LeMoyne
Greenfield Park, Quebec, J4V 2H1
Jewish General Hospital
Montreal, Quebec, H3T 1E2
C.H.A. Enfant-Jesus
Québec, Quebec, G1J 1Z4
CHUS-Hopital Fleurimont
Sherbrooke, Quebec, J1H 5N4
India3 sites
B. P. Poddar Hospital and Medical Research Ltd.
Kolkata, West Bengal, 700053
Jehangir Clinical Development Centre
Pune, Maharashtra, 411001
MMF Joshi Hospital and Ratna Memorial Hospital
Pune, Maharashtra, 411004
Spain3 sites
Hospital Santa Creu I Sant Pau
Barcelona, 08041
Hospital de La Princesa
Madrid, 28006
Hospital Universitario Puerta de Hierro
Majadahonda, Madrid, 28222
Belgium2 sites
Universitair Ziekenhuis Gent
Ghent, 9000
Oncologisch Centrum GZA - Location St. Augustinus
Wilrijk, 2610
Hong Kong2 sites
Queen Mary Hospital
Hong Kong
Prince of Wales Hospital
Shatin, NEW Territories
Argentina1 site
Centro de Transplantes de medula Osea de Rosario, CETRAMOR
Rosario, Santa Fe Province, S2000AYW
Italy1 site
Divisione di Ematologia - Fondazione IRCCS Policlinico San Matteo
Pavia, 27100
Russia1 site
Moscow Regional Research Clinical Institute named after Vladimirsky
Moscow, 120110
South Africa1 site
Wits Donald Gordon Clinical Trial Site
Johannesburg, Gauteng, 2193
South Korea1 site
Yonsei University Health System-Severance Hospital
Seoul, 120-752
About this study
Official title: An Open-label, Randomized, Phase 3 Study Of Inotuzumab Ozogamicin (Cmc-544) Administered In Combination With Rituximab Compared To A Defined Investigator's Choice Therapy In Subjects With Relapsed Or Refractory, Cd22- Positive, Follicular B-cell Non Hodgkin's Lymphoma
This protocol is designed to assess the efficacy and safety of inotuzumab ozogamicin given with rituximab compared to a defined investigator's choice therapy. Subjects will be randomized to one of these two arms of the study.
Read the detailed description
On January 14th 2009, enrollment in the study was discontinued because of poor enrollment and because it was unlikely that the study would meet the estimated enrollment of approximately 978 subjects. The decision was not prompted by the identification of any safety signals in this or other studies. Active treatment and follow-up of the already enrolled subjects was continued. On July, 22th 2010 , the study was amended to shorten the long-term follow-up to one year after active treatment.
- Conditions
- Lymphoma, Follicular
- Being tested
- inotuzumab ozogamicin, rituximab, cyclophosphamide, vincristine, prednisone/prednisolone
- Medical subject headings
- Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
inotuzumab ozogamicinDrug
IV administration, 1.8mg/m² on day 2 of each cycle every 28 days, for up to 8 cycles.
rituximabDrug
IV administration, 375 mg/m² on day 1 of each cycle every 28 days, for up to 8 cycles.
rituximabDrug
intravenous rituximab at a dose of 375 mg/m2 on day 1
cyclophosphamideDrug
intravenous cyclophosphamide at a dose of 750 mg/m2 on day 1
vincristineDrug
intravenous vincristine at a dose of 1.4 mg/m2 (not to exceed 2 mg) on day 1
prednisone/prednisoloneDrug
oral prednisone/prednisolone at a dose of 40 mg/m2 on days 1 through 5
mitoxantroneDrug
mitoxantrone 10 mg/m2 intravenous on day 2
fludarabineDrug
fludarabine 25 mg/m2 intravenous on days 2 through 4
dexamethasoneDrug
oral dexamethasone 20 mg/day on days 1-5
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | Subjects will receive rituximab intravenously at a dose level of 375 mg/m² on day 1 of each cycle followed by inotuzumab ozogamicin administered intravenously at a dose level of 1.8 mg/m2 on day 2. The sequence will be repeated every 28 days. Receives: Drug: inotuzumab ozogamicin; Drug: rituximab |
| B | Active comparator | Subjects will receive the investigator's choice from the following rituximab-containing regimens: R-CVP or R-FND. The investigator's choice of therapy will be administered every 21 days. Dosing for R-CVP will be intravenous rituximab at a dose of 375 mg/m2 on day 1, intravenous cyclophosphamide at a dose of 750 mg/m2 on day 1, intravenous vincristine at a dose of 1.4 mg/m2 (not to exceed 2 mg) on day 1, and oral prednisone/prednisolone at a dose of 40 mg/m2 on days 1 through 5. Dosing for R-FND will be as follows: rituximab 375 mg/m2 intravenous on day 1, mitoxantrone 10 mg/m2 intravenous on day 2, fludarabine 25 mg/m2 intravenous on days 2 through 4 and oral dexamethasone 20 mg/day on days 1-5. Receives: Drug: rituximab; Drug: cyclophosphamide; Drug: vincristine; Drug: prednisone/prednisolone; Drug: mitoxantrone; Drug: fludarabine; Drug: dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-Free Survival (PFS)
PFS was defined as the time from randomization to disease progression or death due to any cause, whichever occurred first, censored at the last tumor evaluation date. PFS calculated as (Months) = (first event date minus randomization date plus 1) divided by 30.44.
Measured: Baseline until disease progression or death or up to 1 year after last dose of study drug
Secondary outcomes (3)
Percentage of Participants With Objective Response (OR)
OR was based on assessment of complete response(CR),unconfirmed CR(Cru),partial response(PR) as per International Response Criteria for Non-Hodgkin's Lymphoma.Confirmed response=response persists on repeat imaging at least 4 weeks after initial response.CR=complete disappearance of all detectable clinical/radiographic evidence of disease,lymph nodes regressed to normal size [at least 1.5 centimeter(cm) or less],spleen regressed,not palpable on physical examination,bone marrow infiltrate cleared on repeat aspiration/biopsy.PR=at least 50 percent (%) decrease in sum of product diameters of 6 greatest dominant nodes,no increase in other nodes,liver/spleen,no new sites of disease. CRu=residual lymph node greater than 1.5 cm in transverse diameter that has regressed more than 75% in product diameter.Individual nodes previously confluent,regressed more than 75% in product diameters.Indeterminate bone marrow (increased number/size of lymph aggregates without cytologic/architectural atypia).
Measured: Baseline, every 6 to 12 weeks during treatment period, end of treatment (EOT) (42 days after last dose), every 12 weeks during follow-up for up to 1 year after the last dose of study drug
Overall Survival Probability at Months 6, 12 and 24
Overall survival was defined as the time from randomization to death due to any cause, censoring at the date of last contact or the end of the study. Participants who withdrew or lost to follow-up from study without having death documented were censored at the date of last contact. Kaplan-Meier estimates of the probability of survival at 6, 12 and 24 months was used to estimate the survival function.
Measured: Baseline up to Month 6, 12, 24
Pharmacokinetics of Inotuzumab Ozogamicin in Combination With Rituximab
Measured: 0, 1, 168 hours on Cycle 1, 2; 0, 1, 2, 168 hours on Cycle 3, 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Nov 2007 (estimated)
- Study startNov 2007
- Primary completionApr 2011
- Study completionApr 2011
Why it stopped: See termination reason in detailed description.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Lymphoma, FollicularStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- UCB Pharma
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00562965
- Sponsor's protocol ID
- 3129K4-3301
- Other IDs
- B1931006, 2007-000219-27
- Status last verified
- Dec 2017
- First submitted
- 21 Nov 2007
- Last updated
- 9 Jan 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Randomized, Phase 3 Study Of Inotuzumab Ozogamicin (Cmc-544) Administered In Combination With Rituximab Compared To A Defined Investigator's Choice Therapy In Subjects With Relapsed Or Refractory, Cd22- Positive, Follicular B-cell Non Hodgkin's Lymphoma
- ClinicalTrials.gov ID
- NCT00562965
- Acronym / sponsor ID
- 3129K4-3301
- Conditions
- Lymphoma, Follicular
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: See termination reason in detailed description.
- Enrolment
- 29 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Collaborators
- UCB Pharma
- Study start
- Nov 2007 (actual)
- Primary completion
- Apr 2011 (actual)
- Study completion
- Apr 2011 (actual)
- First posted
- 26 Nov 2007 (estimated)
- Results
- Posted 9 Jan 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This protocol is designed to assess the efficacy and safety of inotuzumab ozogamicin given with rituximab compared to a defined investigator's choice therapy. Subjects will be randomized to one of these two arms of the study.
Detailed description
On January 14th 2009, enrollment in the study was discontinued because of poor enrollment and because it was unlikely that the study would meet the estimated enrollment of approximately 978 subjects. The decision was not prompted by the identification of any safety signals in this or other studies. Active treatment and follow-up of the already enrolled subjects was continued. On July, 22th 2010 , the study was amended to shorten the long-term follow-up to one year after active treatment.
Study design
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Drug: inotuzumab ozogamicin, Drug: rituximabSubjects will receive rituximab intravenously at a dose level of 375 mg/m² on day 1 of each cycle followed by inotuzumab ozogamicin administered intravenously at a dose level of 1.8 mg/m2 on day 2. The sequence will be repeated every 28 days. |
| B | Active comparator | Drug: rituximab, Drug: cyclophosphamide, Drug: vincristine, Drug: prednisone/prednisolone, Drug: mitoxantrone, Drug: fludarabine, Drug: dexamethasoneSubjects will receive the investigator's choice from the following rituximab-containing regimens: R-CVP or R-FND. The investigator's choice of therapy will be administered every 21 days. Dosing for R-CVP will be intravenous rituximab at a dose of 375 mg/m2 on day 1, intravenous cyclophosphamide at a dose of 750 mg/m2 on day 1, intravenous vincristine at a dose of 1.4 mg/m2 (not to exceed 2 mg) on day 1, and oral prednisone/prednisolone at a dose of 40 mg/m2 on days 1 through 5. Dosing for R-FND will be as follows: rituximab 375 mg/m2 intravenous on day 1, mitoxantrone 10 mg/m2 intravenous on day 2, fludarabine 25 mg/m2 intravenous on days 2 through 4 and oral dexamethasone 20 mg/day on days 1-5. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Subjects with a diagnosis of CD20 and CD22-positive, follicular lymphoma, who have received 1 or 2 prior regimens, at least 1 of which should have contained administration of rituximab (either as a single agent or in combination).
- Age 18 years or older.
- ECOG performance status <= 2.
- ANC >= 1.5 x 10^9/L (1500/mL) and platelets >= 75 x 10^9/L (75,000/mL), serum creatinine <= 1.5 x ULN and urine protein to creatinine ratio of <= 0.5, total bilirubin <= 1.5 x ULN, AST and ALT <= 2.5 x ULN.
- At least 1 measurable disease lesion that is >= 1.5 cm x 1.5 cm by CT or MRI, in an area of no prior radiation therapy, or documented progression in an area that was previously irradiated.
Key exclusion criteria (2 listed)
- Subjects with clinical evidence of transformation to a more aggressive subtype of lymphoma or grade 3b follicular lymphoma.
- Subjects whose disease is rituximab refractory, meaning that they did not have a CR or PR, or that they experienced disease progression within 6 months from the initiation of the rituximab or rituximab containing treatment regimen administered immediately preceding study enrollment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| inotuzumab ozogamicinIV administration, 1.8mg/m² on day 2 of each cycle every 28 days, for up to 8 cycles. | Drug | A |
| rituximabIV administration, 375 mg/m² on day 1 of each cycle every 28 days, for up to 8 cycles. | Drug | A |
| rituximabintravenous rituximab at a dose of 375 mg/m2 on day 1 | Drug | B |
| cyclophosphamideintravenous cyclophosphamide at a dose of 750 mg/m2 on day 1 | Drug | B |
| vincristineintravenous vincristine at a dose of 1.4 mg/m2 (not to exceed 2 mg) on day 1 | Drug | B |
| prednisone/prednisoloneoral prednisone/prednisolone at a dose of 40 mg/m2 on days 1 through 5 | Drug | B |
| mitoxantronemitoxantrone 10 mg/m2 intravenous on day 2 | Drug | B |
| fludarabinefludarabine 25 mg/m2 intravenous on days 2 through 4 | Drug | B |
| dexamethasoneoral dexamethasone 20 mg/day on days 1-5 | Drug | B |
Primary outcome
Progression-Free Survival (PFS)
Time frame: Baseline until disease progression or death or up to 1 year after last dose of study drug
PFS was defined as the time from randomization to disease progression or death due to any cause, whichever occurred first, censored at the last tumor evaluation date. PFS calculated as (Months) = (first event date minus randomization date plus 1) divided by 30.44.
3 secondary outcomes
Percentage of Participants With Objective Response (OR)
Time frame: Baseline, every 6 to 12 weeks during treatment period, end of treatment (EOT) (42 days after last dose), every 12 weeks during follow-up for up to 1 year after the last dose of study drug
Overall Survival Probability at Months 6, 12 and 24
Time frame: Baseline up to Month 6, 12, 24
Pharmacokinetics of Inotuzumab Ozogamicin in Combination With Rituximab
Time frame: 0, 1, 168 hours on Cycle 1, 2; 0, 1, 2, 168 hours on Cycle 3, 4
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
39 sites in 14 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing inotuzumab ozogamicin, rituximab and cyclophosphamide in people with Lymphoma, Follicular, run by Pfizer at 39 sites in 14 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 39 sites in United States, Canada, India, Spain, Belgium and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jan 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-Free Survival (PFS) (time frame: Baseline until disease progression or death or up to 1 year after last dose of study drug). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2018.