Study Comparing Inotuzumab Ozogamicin In Combination With Rituximab Versus Defined Investigator's Choice In Follicular Non-Hodgkin's Lymphoma (NHL) - Full Text View

Purpose

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.

Condition	Intervention	Phase
Lymphoma, Follicular	Drug: inotuzumab ozogamicin Drug: rituximab Drug: cyclophosphamide Drug: vincristine Drug: prednisone/prednisolone Drug: mitoxantrone Drug: fludarabine Drug: dexamethasone	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Health Services Research
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

Resource links provided by NLM:

MedlinePlus related topics: Lymphoma Steroids

Drug Information available for: Dexamethasone Cyclophosphamide Prednisolone Prednisolone acetate Prednisone Methylprednisolone acetate Methylprednisolone Prednisolone sodium phosphate Prednisolone phosphate Dexamethasone acetate Prednisolone sodium succinate Vincristine sulfate Methylprednisolone sodium succinate Dexamethasone sodium phosphate Fludarabine Mitoxantrone Mitoxantrone hydrochloride Fludarabine phosphate Rituximab

U.S. FDA Resources

Further study details as provided by Pfizer:

Primary Outcome Measures:

To assess efficacy as measured by progression free survival (PFS), with a goal of demonstrating the superiority of inotuzumab ozogamicin when administered in combination with rituximab, compared with an active comparator arm. [ Time Frame: 4 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To assess the safety and tolerability of inotuzumab ozogamicin in combination with rituximab. To assess the population pharmacokinetics (PK) of inotuzumab ozogamicin in combination with rituximab, and to evaluate factors affecting drug metabolism. [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
To evaluate the efficacy of inotuzumab ozogamicin in combination with rituximab using the following endpoints and analyses: Overall Response Rate and Overall Survival [ Time Frame: 4 years ] [ Designated as safety issue: No ]
QT assessment [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]

Enrollment:	29
Study Start Date:	November 2007
Study Completion Date:	April 2011
Primary Completion Date:	April 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: A 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.	Drug: inotuzumab ozogamicin IV administration, 1.8mg/m² on day 2 of each cycle every 28 days, for up to 8 cycles. Drug: rituximab IV administration, 375 mg/m² on day 1 of each cycle every 28 days, for up to 8 cycles.
Active Comparator: B 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.	Drug: rituximab intravenous rituximab at a dose of 375 mg/m2 on day 1 Drug: cyclophosphamide intravenous cyclophosphamide at a dose of 750 mg/m2 on day 1 Drug: vincristine intravenous vincristine at a dose of 1.4 mg/m2 (not to exceed 2 mg) on day 1 Drug: prednisone/prednisolone oral prednisone/prednisolone at a dose of 40 mg/m2 on days 1 through 5 Drug: mitoxantrone mitoxantrone 10 mg/m2 intravenous on day 2 Drug: fludarabine fludarabine 25 mg/m2 intravenous on days 2 through 4 Drug: dexamethasone oral dexamethasone 20 mg/day on days 1-5

Arms

Assigned Interventions

Experimental: A

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.

Drug: inotuzumab ozogamicin

IV administration, 1.8mg/m² on day 2 of each cycle every 28 days, for up to 8 cycles.

Drug: rituximab

IV administration, 375 mg/m² on day 1 of each cycle every 28 days, for up to 8 cycles.

Active Comparator: B

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.

Drug: rituximab

intravenous rituximab at a dose of 375 mg/m2 on day 1

Drug: cyclophosphamide

intravenous cyclophosphamide at a dose of 750 mg/m2 on day 1

Drug: vincristine

intravenous vincristine at a dose of 1.4 mg/m2 (not to exceed 2 mg) on day 1

Drug: prednisone/prednisolone

oral prednisone/prednisolone at a dose of 40 mg/m2 on days 1 through 5

Drug: mitoxantrone

mitoxantrone 10 mg/m2 intravenous on day 2

Drug: fludarabine

fludarabine 25 mg/m2 intravenous on days 2 through 4

Drug: dexamethasone

oral dexamethasone 20 mg/day on days 1-5

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00562965

Show 38 Study Locations

Sponsors and Collaborators

Pfizer

UCB, Inc.

Investigators

Study Director:

Pfizer CT.gov Call Center

Pfizer

More Information

Additional Information:

To obtain contact information for a study center near you, click here. This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Pfizer
ClinicalTrials.gov Identifier:	NCT00562965 History of Changes
Other Study ID Numbers:	3129K4-3301, B1931006
Study First Received:	November 21, 2007
Last Updated:	December 22, 2012
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Fludarabine monophosphate
Rituximab
Fludarabine
Dexamethasone

Prednisolone
Methylprednisolone Hemisuccinate
Mitoxantrone
Prednisone
Vincristine
Dexamethasone acetate
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Dexamethasone 21-phosphate
Prednisolone hemisuccinate
Prednisolone phosphate
BB 1101
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on June 13, 2013