Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab in Treating Patients With Previously Untreated Marginal Zone Lymphoma

• Sponsor: University of Miami (Other)
• Overall Status: Completed
• CT.gov ID: NCT00453102
• Collaborator: (none)
• Enrollment: 18
• Location: 1
• Arm: 1
• Duration (Months): 108
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Zevalin may be an effective therapy for newly diagnosed marginal zone lymphoma (MZL).

Condition or Disease	Intervention/Treatment	Phase
Marginal Zone Lymphoma	Drug: Rituximab; Drug: Ibritumomab Tiuxetan	Phase 2

Detailed Description

This phase II study will assess the clinical response rate to Ibritumomab Tiuxetan in patients with untreated nodal, splenic and non-gastric extranodal MZL as well as in antibiotic resistant patients with mucosa-associated lymphoid tissue (MALT) gastric lymphoma.

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Ibritumomab Tiuxetan (Zevalin®) in Patients With Previously Untreated Marginal Zone Lymphoma
• Study Start Date: Feb 1, 2006
• Actual Primary Completion Date: Feb 1, 2015
• Actual Study Completion Date: Feb 1, 2015

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Zevalin + Rituximab Ibritumomab Tiuxetan (Zevalin) + Rituximab

Drug: Rituximab; IV Infusion of 250mg/m² of Rituximab Within 4 hours on Days 1, 7, 8, 9 0.4 millicuries (mCi)/kilogram (kg) (14.8 megabecquerels (MBq)/kilogram (kg)) for patients with normal platelet count 0.3 mCi/kg (11.1 MBq/kg) for patients with platelet count of 100,000-149,000 cells/mm³; Other Names: Rituxan IDEC-C2B8 Chimeric anti-CD20 monoclonal antibody ; Drug: Ibritumomab Tiuxetan; IV injection of Y-90 Zevalin® over 10 minutes on Days 1, 7, 8, 9: 0.4 mCi/kg (14.8 MBq/kg) for patients with normal platelet count 0.3 mCi/kg (11.1 MBq/kg) for patients with platelet count of 100,000-149,000 cells/mm³; Other Names: Zevalin

Outcome Measures

Primary Outcome Measures

1. Overall Rate of Response (ORR) in Participants Receiving Protocol Therapy. [12 weeks post-therapy]

   The overall response rate (ORR) including complete response (CR), complete response unconfirmed (CRu), and partial response (PR) in participants receiving protocol therapy.

Secondary Outcome Measures

1. Rate of Progression-Free Survival [End of study.]

   The time from the start of protocol therapy until the first documented or confirmed disease progression, or death related to study disease, whichever is earlier.

2. 5-Year Rate of Progression-Free Survival (5-Year PFS) [5 Years]

   Percentage of participants still alive without disease progression five years after the date of protocol therapy initiation.

3. Overall Survival (OS) Rate [End of Study]

   The time from the date of initiation of study treatment until date of death from any cause for all participants.

4. 5 Year Rate of Overall Survival (5-Year OS) [5 Years]

   Percentage of participants still alive five years after the date of protocol therapy initiation.

5. Number of Participants With Unacceptable Toxicity. [Up to 12 weeks post-therapy]

   Number of participants with treatment-related (possible, probable, or definite) grade 3 or higher non-hematologic adverse events.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• ≥ 18 years old with previously untreated, histologically confirmed Marginal Zone Lymphoma (non-gastric extranodal MZL, splenic MZL and nodal MZL) or gastric MZL that did not respond to antibiotic therapy given up to 6 months prior to enrollment, but not less than 2 months)

• Measurable and evaluable disease

• All stages are eligible

• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2 (Appendix B)

• Willing and able to provide written informed consent

• Women of childbearing potential must have a negative pregnancy test at study entry and must agree to use effective contraception while on treatment and for 6 months after treatment

• Life expectancy of at least 6 months

Exclusion Criteria:

• Prior chemotherapy, radiation therapy, immunotherapy, systemic corticosteroids, or systemic biologic anticancer therapy before beginning study treatment.

• ≥ 25% lymphoma bone marrow involvement

• Platelet count < 100,000 cells/mm³

• Neutrophil count < 1,500 cells/mm³

• Known history of HIV infection

• Pregnant or lactating (pregnancy test is required for all female patients of childbearing potential)

• Woman of childbearing potential or sexually active man unwilling to use adequate contraceptive protection.

• Physical or mental condition that makes patient unable to complete specified follow-up assessments

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Miami Sylvester Comprehensive Cancer Center - Miami	Miami	Florida	United States	33136

Sponsors and Collaborators

• University of Miami

Investigators

• Study Chair: Izidore S. Lossos, MD, University of Miami Sylvester Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

• Lossos IS, Fabregas JC, Koru-Sengul T, Miao F, Goodman D, Serafini AN, Hosein PJ, Stefanovic A, Rosenblatt JD, Hoffman JE. Phase II study of (90)Y Ibritumomab tiuxetan (Zevalin) in patients with previously untreated marginal zone lymphoma. Leuk Lymphoma. 2015 Jun;56(6):1750-5. doi: 10.3109/10428194.2014.975801. Epub 2014 Nov 20.

• Responsible Party: Izidore Lossos, Professor, University of Miami
• ClinicalTrials.gov Identifier: NCT00453102
• Other Study ID Numbers: 20060078; SCCC-2005133; WIRB-20060249
• First Posted: Mar 28, 2007
• Last Update Posted: Jan 1, 2016
• Last Verified: Nov 1, 2015

• Keywords provided by Izidore Lossos, Professor, University of Miami: Marginal Zone Lymphoma; Non-gastric extranodal Marginal Zone Lymphoma; Splenic Marginal Zone Lymphoma; Nodal Marginal Zone Lymphoma; Gastric Marginal Zone Lymphoma; MZL; Non-gastric extranodal MZL; Splenic MZL; Nodal MZL; Gastric MZL
• Additional relevant MeSH terms: Lymphoma; Lymphoma, B-Cell, Marginal Zone; Rituximab

Study Results

Participant Flow

Arm/Group Title	Zevalin + Rituximab
Arm/Group Description	Ibritumomab Tiuxetan (Zevalin) + Rituximab Rituximab: IV Infusion of 250mg/m² of Rituximab Within 4 hours on Days 1, 7, 8, 9 0.4 millicuries (mCi)/kilogram (kg) (14.8 megabecquerels (MBq)/kilogram (kg)) for patients with normal platelet count 0.3 mCi/kg (11.1 MBq/kg) for patients with platelet count of 100,000-149,000 cells/mm³ Ibritumomab Tiuxetan: IV injection of Y-90 Zevalin® over 10 minutes on Days 1, 7, 8, 9: 0.4 mCi/kg (14.8 MBq/kg) for patients with normal platelet count 0.3 mCi/kg (11.1 MBq/kg) for patients with platelet count of 100,000-149,000 cells/mm³
Period Title: Overall Study
STARTED	18
COMPLETED	16
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Zevalin + Rituximab
Arm/Group Description	Ibritumomab Tiuxetan (Zevalin) + Rituximab Rituximab: IV Infusion of 250mg/m² of Rituximab Within 4 hours on Days 1, 7, 8, 9 0.4 millicuries (mCi)/kilogram (kg) (14.8 megabecquerels (MBq)/kilogram (kg)) for patients with normal platelet count 0.3 mCi/kg (11.1 MBq/kg) for patients with platelet count of 100,000-149,000 cells/mm³ Ibritumomab Tiuxetan: IV injection of Y-90 Zevalin® over 10 minutes on Days 1, 7, 8, 9: 0.4 mCi/kg (14.8 MBq/kg) for patients with normal platelet count 0.3 mCi/kg (11.1 MBq/kg) for patients with platelet count of 100,000-149,000 cells/mm³
Overall Participants	16
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	62
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62 (13)
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	62
Sex: Female, Male (Count of Participants)
Female	7 43.8%
Male	9 56.3%
Disease Stage (participants) [Number]
Stage I/II	3 18.8%
Stage III/IV	13 81.3%
Extranodal disease sites (participants) [Number]
0, 1 sites	11 68.8%
2 or more sites	5 31.3%
Eastern Cooperative Oncology Group (ECOG) Performance Status (participants) [Number]
0	14 87.5%
1	2 12.5%
2	0 0%
Bone Marrow involvement (participants) [Number]
Yes	0 0%
No	16 100%
Lactate dehydrogenase (LDH) Levels (participants) [Number]
Normal	14 87.5%
Elevated	2 12.5%
Bulky disease (cm) (participants) [Number]
5 and less cm	9 56.3%
More than 5 cm	7 43.8%
International Prognostic Index (IPI) Risk Group (participants) [Number]
Low risk	3 18.8%
Low/intermediate risk	9 56.3%
Intermediate/high risk	4 25%
High risk	0 0%
Follicular Lymphoma International Prognostic Index (FLIPI) Risk Group (participants) [Number]
Low risk	7 43.8%
Intermediate risk	7 43.8%
High risk	2 12.5%

Outcome Measures

1. Primary Outcome

Title	Overall Rate of Response (ORR) in Participants Receiving Protocol Therapy.
Description	The overall response rate (ORR) including complete response (CR), complete response unconfirmed (CRu), and partial response (PR) in participants receiving protocol therapy.
Time Frame	12 weeks post-therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Zevalin + Rituximab
Arm/Group Description	Ibritumomab Tiuxetan (Zevalin) + Rituximab Rituximab: IV Infusion of 250mg/m² of Rituximab Within 4 hours on Days 1, 7, 8, 9 0.4 millicuries (mCi)/kilogram (kg) (14.8 megabecquerels (MBq)/kilogram (kg)) for patients with normal platelet count 0.3 mCi/kg (11.1 MBq/kg) for patients with platelet count of 100,000-149,000 cells/mm³ Ibritumomab Tiuxetan: IV injection of Y-90 Zevalin® over 10 minutes on Days 1, 7, 8, 9: 0.4 mCi/kg (14.8 MBq/kg) for patients with normal platelet count 0.3 mCi/kg (11.1 MBq/kg) for patients with platelet count of 100,000-149,000 cells/mm³
Measure Participants	16
Number (90% Confidence Interval) [percentage of participants]	87.5 546.9%

2. Secondary Outcome

Title	Rate of Progression-Free Survival
Description	The time from the start of protocol therapy until the first documented or confirmed disease progression, or death related to study disease, whichever is earlier.
Time Frame	End of study.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Zevalin + Rituximab
Arm/Group Description	Ibritumomab Tiuxetan (Zevalin) + Rituximab Rituximab: IV Infusion of 250mg/m² of Rituximab Within 4 hours on Days 1, 7, 8, 9 0.4 millicuries (mCi)/kilogram (kg) (14.8 megabecquerels (MBq)/kilogram (kg)) for patients with normal platelet count 0.3 mCi/kg (11.1 MBq/kg) for patients with platelet count of 100,000-149,000 cells/mm³ Ibritumomab Tiuxetan: IV injection of Y-90 Zevalin® over 10 minutes on Days 1, 7, 8, 9: 0.4 mCi/kg (14.8 MBq/kg) for patients with normal platelet count 0.3 mCi/kg (11.1 MBq/kg) for patients with platelet count of 100,000-149,000 cells/mm³
Measure Participants	16
Median (Full Range) [months]	47.6

3. Secondary Outcome

Title	5-Year Rate of Progression-Free Survival (5-Year PFS)
Description	Percentage of participants still alive without disease progression five years after the date of protocol therapy initiation.
Time Frame	5 Years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Zevalin + Rituximab
Arm/Group Description	Ibritumomab Tiuxetan (Zevalin) + Rituximab Rituximab: IV Infusion of 250mg/m² of Rituximab Within 4 hours on Days 1, 7, 8, 9 0.4 millicuries (mCi)/kilogram (kg) (14.8 megabecquerels (MBq)/kilogram (kg)) for patients with normal platelet count 0.3 mCi/kg (11.1 MBq/kg) for patients with platelet count of 100,000-149,000 cells/mm³ Ibritumomab Tiuxetan: IV injection of Y-90 Zevalin® over 10 minutes on Days 1, 7, 8, 9: 0.4 mCi/kg (14.8 MBq/kg) for patients with normal platelet count 0.3 mCi/kg (11.1 MBq/kg) for patients with platelet count of 100,000-149,000 cells/mm³
Measure Participants	16
Number (90% Confidence Interval) [percentage of participants]	40 250%

4. Secondary Outcome

Title	Overall Survival (OS) Rate
Description	The time from the date of initiation of study treatment until date of death from any cause for all participants.
Time Frame	End of Study

Outcome Measure Data

Analysis Population Description

Median overall survival by Kaplan-Meier method for all patients was not attained.

Arm/Group Title	Zevalin + Rituximab
Arm/Group Description	Ibritumomab Tiuxetan (Zevalin) + Rituximab Rituximab: IV Infusion of 250mg/m² of Rituximab Within 4 hours on Days 1, 7, 8, 9 0.4 millicuries (mCi)/kilogram (kg) (14.8 megabecquerels (MBq)/kilogram (kg)) for patients with normal platelet count 0.3 mCi/kg (11.1 MBq/kg) for patients with platelet count of 100,000-149,000 cells/mm³ Ibritumomab Tiuxetan: IV injection of Y-90 Zevalin® over 10 minutes on Days 1, 7, 8, 9: 0.4 mCi/kg (14.8 MBq/kg) for patients with normal platelet count 0.3 mCi/kg (11.1 MBq/kg) for patients with platelet count of 100,000-149,000 cells/mm³
Measure Participants	16
Number [months]	NA

5. Secondary Outcome

Title	5 Year Rate of Overall Survival (5-Year OS)
Description	Percentage of participants still alive five years after the date of protocol therapy initiation.
Time Frame	5 Years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Zevalin + Rituximab
Arm/Group Description	Ibritumomab Tiuxetan (Zevalin) + Rituximab Rituximab: IV Infusion of 250mg/m² of Rituximab Within 4 hours on Days 1, 7, 8, 9 0.4 millicuries (mCi)/kilogram (kg) (14.8 megabecquerels (MBq)/kilogram (kg)) for patients with normal platelet count 0.3 mCi/kg (11.1 MBq/kg) for patients with platelet count of 100,000-149,000 cells/mm³ Ibritumomab Tiuxetan: IV injection of Y-90 Zevalin® over 10 minutes on Days 1, 7, 8, 9: 0.4 mCi/kg (14.8 MBq/kg) for patients with normal platelet count 0.3 mCi/kg (11.1 MBq/kg) for patients with platelet count of 100,000-149,000 cells/mm³
Measure Participants	16
Number (90% Confidence Interval) [percentage of participants]	71.8 448.8%

6. Secondary Outcome

Title	Number of Participants With Unacceptable Toxicity.
Description	Number of participants with treatment-related (possible, probable, or definite) grade 3 or higher non-hematologic adverse events.
Time Frame	Up to 12 weeks post-therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Zevalin + Rituximab
Arm/Group Description	Ibritumomab Tiuxetan (Zevalin) + Rituximab Rituximab: IV Infusion of 250mg/m² of Rituximab Within 4 hours on Days 1, 7, 8, 9 0.4 millicuries (mCi)/kilogram (kg) (14.8 megabecquerels (MBq)/kilogram (kg)) for patients with normal platelet count 0.3 mCi/kg (11.1 MBq/kg) for patients with platelet count of 100,000-149,000 cells/mm³ Ibritumomab Tiuxetan: IV injection of Y-90 Zevalin® over 10 minutes on Days 1, 7, 8, 9: 0.4 mCi/kg (14.8 MBq/kg) for patients with normal platelet count 0.3 mCi/kg (11.1 MBq/kg) for patients with platelet count of 100,000-149,000 cells/mm³
Measure Participants	16
Number [participants]	2 12.5%

Adverse Events

Arm/Group Title	Zevalin + Rituximab
Arm/Group Description	Ibritumomab Tiuxetan (Zevalin) + Rituximab Rituximab: IV Infusion of 250mg/m² of Rituximab Within 4 hours on Days 1, 7, 8, 9 0.4 millicuries (mCi)/kilogram (kg) (14.8 megabecquerels (MBq)/kilogram (kg)) for patients with normal platelet count 0.3 mCi/kg (11.1 MBq/kg) for patients with platelet count of 100,000-149,000 cells/mm³ Ibritumomab Tiuxetan: IV injection of Y-90 Zevalin® over 10 minutes on Days 1, 7, 8, 9: 0.4 mCi/kg (14.8 MBq/kg) for patients with normal platelet count 0.3 mCi/kg (11.1 MBq/kg) for patients with platelet count of 100,000-149,000 cells/mm³
All Cause Mortality
	Zevalin + Rituximab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Zevalin + Rituximab
	Affected / at Risk (%)	# Events
Total	2/16 (12.5%)
Gastrointestinal disorders
Abdominal Pain (Grade 3)	1/16 (6.3%)	1
General disorders
Fatigue (Grade 3)	1/16 (6.3%)	1
Infections and infestations
Sepsis (Grade 5)	1/16 (6.3%)	1
Respiratory, thoracic and mediastinal disorders
Upper Respiratory Infection (Grade 3)	1/16 (6.3%)	1
Other (Not Including Serious) Adverse Events
	Zevalin + Rituximab
	Affected / at Risk (%)	# Events
Total	15/16 (93.8%)
Blood and lymphatic system disorders
Edema limbs	1/16 (6.3%)	1
Hemoglobin	9/16 (56.3%)	21
Leukocytes	15/16 (93.8%)	61
Lymphopenia	8/16 (50%)	18
Myelodysplasia	1/16 (6.3%)	1
Neutrophils	9/16 (56.3%)	29
Petechiae	1/16 (6.3%)	1
Platelets	14/16 (87.5%)	29
PTT	1/16 (6.3%)	1
Cardiac disorders
Palpitations	1/16 (6.3%)	1
Eye disorders
Blurred vision	1/16 (6.3%)	1
Dry eye syndrome	1/16 (6.3%)	1
Gastrointestinal disorders
Abdominal Pain (Grade 1-2)	3/16 (18.8%)	4
Anorexia	1/16 (6.3%)	1
Back Pain	2/16 (12.5%)	2
Dehydration	1/16 (6.3%)	1
Diarrhea	1/16 (6.3%)	2
Dry mouth	2/16 (12.5%)	2
Dysphagia	1/16 (6.3%)	1
Gastritis	2/16 (12.5%)	2
Hemorrhoids	1/16 (6.3%)	2
Nausea	4/16 (25%)	4
Vomiting	3/16 (18.8%)	3
General disorders
Fatigue	6/16 (37.5%)	8
Fever	6/16 (37.5%)	8
Headache	3/16 (18.8%)	4
Joint Pain	3/16 (18.8%)	3
Myalgia	3/16 (18.8%)	3
Neuralgia	1/16 (6.3%)	1
Pain in extremity	2/16 (12.5%)	2
Rigors/chills	1/16 (6.3%)	1
Sweating	1/16 (6.3%)	1
Tooth disorder	1/16 (6.3%)	1
Immune system disorders
Rhinitis	2/16 (12.5%)	2
Infections and infestations
Febrile neutropenia	1/16 (6.3%)	1
Hepatic infection	1/16 (6.3%)	1
Upper respiratory infection	4/16 (25%)	4
Injury, poisoning and procedural complications
Allergic Reaction	3/16 (18.8%)	3
Metabolism and nutrition disorders
Alkaline phosphatase increased	2/16 (12.5%)	6
Creatinine increased	2/16 (12.5%)	2
Hyperglycemia	7/16 (43.8%)	15
Hypermagnesemia	1/16 (6.3%)	1
Hypoalbuminemia	2/16 (12.5%)	3
Hypoglycemia	1/16 (6.3%)	1
Hypokalemia	1/16 (6.3%)	1
Hypomagnesemia	1/16 (6.3%)	1
Metabolic/Lab - Other(Specify)	6/16 (37.5%)	17
Musculoskeletal and connective tissue disorders
Arthritis (non-septic)	1/16 (6.3%)	1
Fracture	1/16 (6.3%)	1
Joint-function	1/16 (6.3%)	1
Muscle weakness	3/16 (18.8%)	3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Treatment related secondary malignancy	2/16 (12.5%)	2
Nervous system disorders
Anxiety	1/16 (6.3%)	1
Depression	1/16 (6.3%)	1
Dizziness	1/16 (6.3%)	1
Facial nerve disorder	1/16 (6.3%)	1
Peripheral sensory neuropathy	1/16 (6.3%)	1
Renal and urinary disorders
Urinary frequency	1/16 (6.3%)	1
Reproductive system and breast disorders
Vaginal hemorrhage	1/16 (6.3%)	1
Respiratory, thoracic and mediastinal disorders
Atelectasis	1/16 (6.3%)	1
Bronchial obstruction	1/16 (6.3%)	1
Bronchitis	1/16 (6.3%)	1
Bronchospasm	1/16 (6.3%)	2
Cough	3/16 (18.8%)	4
Dyspnea	2/16 (12.5%)	5
Hemorrhage nasal	1/16 (6.3%)	1
Infection, Upper airway NOS	1/16 (6.3%)	1
Skin and subcutaneous tissue disorders
Bruising	4/16 (25%)	4
Dry skin	1/16 (6.3%)	1
Infection, Skin (cellulites)	1/16 (6.3%)	1
Rash	4/16 (25%)	4
Vascular disorders
Hematoma	1/16 (6.3%)	2
Thrombosis/embolism (vascular access)	1/16 (6.3%)	1

Limitations/Caveats

Data reported for only 16 of 18 enrolled participants due to 2 participants withdrawing consent.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.