Zevalin (Ibritumomab Tiuxetan) for Early Stage Indolent Lymphomas

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00493467
• Collaborator: Biogen (Industry), CTI BioPharma (Industry)
• Enrollment: 31
• Location: 1
• Arm: 1
• Duration (Months): 106
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The goal of this clinical research study is to find out if giving (Rituxan) rituximab with 90Y (ibritumomab tiuxetan) (90 Y Zevalin®) may be effective in treating low-grade lymphoma. The safety of this combination treatment will also be studied.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Drug: Ibritumomab Tiuxetan (Zevalin); Drug: Rituximab	Phase 2

Detailed Description

90 Y Zevalin and rituximab are both designed to attach to lymphoma cells, causing them to die.

Before you can start treatment on this study, you will have "screening tests." These tests will help the doctor decide if you are eligible to take part in this study. You will have a physical exam. Blood (about 2 to 3 teaspoons) and urine will be collected for routine tests. You will have a chest x-ray and computerized tomography (CT) scans of the neck, chest, abdomen (stomach area), and pelvis.

A PET scan is also recommended. A PET (Positron Emission Tomography) scan is a medical technique that monitors the activity in the brain and other organs by tracking the movement of a special radioactive solution through the body. The radioactive solution is either inhaled as a mist or injected into a vein. The radioactive solution is usually made from simple sugar that has radioactive particles attached to it. After the solution is injected into a vein or inhaled, the PET scanner takes pictures of the radioactive solution as it moves through the body and collects in various organs. By watching how the solution travels through the body and studying where the solution collects, researchers can learn the extent of disease in certain organs in the body.

You will have an electrocardiogram (ECG -- a test that measures the electrical activity of the heart). You will have a bone marrow aspirate and biopsy performed. To collect a bone marrow aspirate and biopsy, an area of the hip or chest bone is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle. Women who are able to have children must have a negative blood or urine pregnancy test.

If you are found to be eligible to take part in this study, you will be given diphenhydramine (Benadryl) by vein and you will take acetaminophen (Tylenol) by mouth before each dose of rituximab. This is done to help decrease the risk of developing side effects of rituximab. You will then receive 1 dose of rituximab by vein over about 4-6 hours on Day 1 of treatment. After treatment with rituximab, you will then be given 111 In Zevalin (this is a radioactive agent that binds to rituximab to help with imaging exams), by vein over about 10 minutes. This is so researchers can use a special camera to see where the drug is in your body.

You will have imaging performed (on a camera, like an x-ray) on either Day 2 or 3. On Day 8 (7 days after the first dose of rituximab) you will receive a second dose of rituximab. You will also be given Benadryl, Tylenol, and 90Y Zevalin in the same manner as on Day 1.

If you experience intolerable side effects while on this study, you may be removed from this study. Your treatment on the study will end on Day 8.

You will return for follow-up tests for 4 years. Blood (about 2 tablespoons) will be drawn weekly for the first 3 months. Blood (about 2 tablespoons each time) will also be drawn at month 6 and 9 of the first year, and every 6 months in the second, third, and fourth years. You may also have CT scans, PET scans (which are recommended), x-rays, and bone marrow biopsies and aspirates performed, if your doctor thinks they are necessary.

Your participation on this study will end in about 4 years.

This is an investigational study. 90 Y Zevalin and rituximab are FDA approved and commercially available. Their use in this study is investigational. Up to 36 patients will take part in this multicenter study. Up to 36 patients will be enrolled at M. D. Anderson.

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Zevalin for the Treatment of Early-Stage Indolent Lymphomas
• Study Start Date: Jun 1, 2006
• Actual Primary Completion Date: Apr 1, 2015
• Actual Study Completion Date: Apr 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Zevalin Ibritumomab Tiuxetan (Zevalin) + Rituximab	Drug: Ibritumomab Tiuxetan (Zevalin); 111In Zevalin (5 mCi of ^111In, 1.6 mg of Ibritumomab Tiuxetan) Intravenously Over 10 minutes on Day 1. 90Y Zevalin 0.3 or 0.4 mCi/kg Intravenously Over 10 minutes on Day 8.; Other Names: Ibritumomab Zevalin IDEC-Y2B8 ; Drug: Rituximab; 250 mg/m^2 Intravenously Over 4-6 Hours On Days 1 and 8.; Other Names: Rituxan

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate (ORR) [Up to 5 years; Evaluation at 3-month intervals during Year 1, then every 6 months to Year 4. The median follow-up was 56 months for censored observations.]

   ORR defined as the percentage of number of complete response (CR), complete response unconfirmed (CRu) or partial response (PR) in patients treated using International Working Group (IWG) revised response criteria for Malignant Lymphoma. ORR to therapy is evaluated after three months using radiographic and clinical parameters to assess response. CR: Complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms. CRu: A residual lymph node mass greater than 1.5 cm in greatest transverse diameter that has regressed by more than 75% in the sum of the products of the greatest diameters (SPD). Individual nodes that were previously confluent must have regressed by more than 75% in their SPD compared to the original mass and indeterminate bone marrow. PR: ≥ 50% decrease in SPD of the six largest dominant nodes or nodal masses. No increase in the size of other nodes, liver or spleen and no new sites of disease.

Secondary Outcome Measures

1. Progression Free Survival (PFS) Rate at 3 Years [Evaluation at 3-month intervals during the first year and then every 6 months until year 3]

   PFS measured, in a responder, from the date when a CR, CRu or PR is first noted to the first date at which progressive disease is observed or death. An ongoing PFS interval occurs when there is a responder for whom progressive disease has not been noted. Progression of disease defined as enlargement of liver/spleen, new sites observed, new or increased lymph nodes or lymph node masses, or reappearance of bone marrow.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. New diagnosis of low-grade indolent lymphomas Stage I-II. Patients with multiple skin lesions will be eligible provided that the skin is the only site of involvement.

2. Histology includes Indolent cluster of differentiation antigen 20 (CD20)+ lymphomas including: Follicular lymphoma, Extranodal marginal lymphoma of MALT type, Nodal Marginal zone B-cell lymphoma (+/- monocytoid cells), and Splenic marginal B-cell lymphoma (+/- villous lymphocytes).

3. Signed Informed Consent.

4. Age >/= 18 years.

5. Pre-study Zubrod performance status of 0, 1, or 2.

6. Acceptable hematologic status within two weeks prior to patient registration, including: absolute neutrophil count ([segmented neutrophils + bands] x total WBC) >/= 1, 500/mm^{3, total lymphocyte count </= 5,000/mm}3 and platelet counts >/= 100,000/mm^3.

7. Female patients who are not pregnant or lactating.

8. Men and women of reproductive potential who are following accepted birth control methods (as determined by the treating physician, however abstinence is not an acceptable method).

9. Patients determined to have < 25% bone marrow involvement with lymphoma within six weeks of registration (define measurement of a bone marrow aspirate or biopsy).

10. Patient should have at least one lesion measuring >/= 1.5 cm in a single dimension. Measurable cutaneous lesions are allowed.

Exclusion Criteria:

1. Presence of central nervous system (CNS) lymphoma.

2. Patients with HIV or AIDS-related lymphoma.

3. Patients with pleural effusion.

4. Patients with abnormal liver function: total bilirubin > 2.0 mg/dL.

5. Patients with abnormal renal function: serum creatinine > 2.0 mg/dL.

6. Patients who have received prior external beam radiation therapy to > 25% of active bone marrow (involved field or regional).

7. Impaired bone marrow reserve as indicated by < 15% bone marrow cellularity

8. Serious nonmalignant disease or infection which, in the opinion of the investigator and/or the sponsor, would compromise other protocol objectives.

9. Major surgery, other than diagnostic surgery, within four weeks.

10. Evidence of transformation in the latest biopsy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• Biogen
• CTI BioPharma

Investigators

• Principal Investigator: Felipe Samaniego, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• University of Texas MD Anderson Cancer Center Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT00493467
• Other Study ID Numbers: 2005-0512; NCI-2012-01569
• First Posted: Jun 28, 2007
• Last Update Posted: Sep 1, 2020
• Last Verified: Aug 1, 2020

• Keywords provided by M.D. Anderson Cancer Center: Non-Hodgkin's Lymphoma; Lymphoma; Indolent Lymphomas; Ibritumomab Tiuxetan; Zevalin
• Additional relevant MeSH terms: Lymphoma; Rituximab

Study Results

Participant Flow

Recruitment Details	Recruitment Period: June 12, 2006 to May 08, 2009. All recruitment was done at The University of Texas (UT) MD Anderson Cancer Center.

Arm/Group Title	Zevalin
Arm/Group Description	Ibritumomab Tiuxetan (Zevalin): 111In Zevalin (5 mCi of ^111In, 1.6 mg of Ibritumomab Tiuxetan) intravenous (IV) over 10 minutes on Day 1; 90Y Zevalin 0.3 or 0.4 mCi/kg IV over 10 minutes on Day 8. Rituximab: 250 mg/m^2 IV over 4-6 Hours on Days 1 and 8 prior to the administration of 111In Zevalin and 90Y Zevalin, respectively.
Period Title: Overall Study
STARTED	31
COMPLETED	30
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Zevalin
Arm/Group Description	Ibritumomab Tiuxetan (Zevalin): 111In Zevalin (5 mCi of ^111In, 1.6 mg of Ibritumomab Tiuxetan) intravenous (IV) over 10 minutes on Day 1; 90Y Zevalin 0.3 or 0.4 mCi/kg IV over 10 minutes on Day 8. Rituximab: 250 mg/m^2 IV over 4-6 Hours on Days 1 and 8 prior to the administration of 111In Zevalin and 90Y Zevalin, respectively.
Overall Participants	31
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	60
Sex: Female, Male (Count of Participants)
Female	19 61.3%
Male	12 38.7%
Region of Enrollment (participants) [Number]
United States	31 100%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate (ORR)
Description	ORR defined as the percentage of number of complete response (CR), complete response unconfirmed (CRu) or partial response (PR) in patients treated using International Working Group (IWG) revised response criteria for Malignant Lymphoma. ORR to therapy is evaluated after three months using radiographic and clinical parameters to assess response. CR: Complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms. CRu: A residual lymph node mass greater than 1.5 cm in greatest transverse diameter that has regressed by more than 75% in the sum of the products of the greatest diameters (SPD). Individual nodes that were previously confluent must have regressed by more than 75% in their SPD compared to the original mass and indeterminate bone marrow. PR: ≥ 50% decrease in SPD of the six largest dominant nodes or nodal masses. No increase in the size of other nodes, liver or spleen and no new sites of disease.
Time Frame	Up to 5 years; Evaluation at 3-month intervals during Year 1, then every 6 months to Year 4. The median follow-up was 56 months for censored observations.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Zevalin
Arm/Group Description	Ibritumomab Tiuxetan (Zevalin): 111In Zevalin (5 mCi of ^111In, 1.6 mg of Ibritumomab Tiuxetan) intravenous (IV) over 10 minutes on Day 1; 90Y Zevalin 0.3 or 0.4 mCi/kg IV over 10 minutes on Day 8. Rituximab: 250 mg/m^2 IV over 4-6 Hours on Days 1 and 8 prior to the administration of 111In Zevalin and 90Y Zevalin, respectively.
Measure Participants	31
Complete Response	67.7 218.4%
Complete Response Unconfirmed	29.0 93.5%
Partial Response	3.3 10.6%

2. Secondary Outcome

Title	Progression Free Survival (PFS) Rate at 3 Years
Description	PFS measured, in a responder, from the date when a CR, CRu or PR is first noted to the first date at which progressive disease is observed or death. An ongoing PFS interval occurs when there is a responder for whom progressive disease has not been noted. Progression of disease defined as enlargement of liver/spleen, new sites observed, new or increased lymph nodes or lymph node masses, or reappearance of bone marrow.
Time Frame	Evaluation at 3-month intervals during the first year and then every 6 months until year 3

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Zevalin
Arm/Group Description	Ibritumomab Tiuxetan (Zevalin): 111In Zevalin (5 mCi of ^111In, 1.6 mg of Ibritumomab Tiuxetan) intravenous (IV) over 10 minutes on Day 1; 90Y Zevalin 0.3 or 0.4 mCi/kg IV over 10 minutes on Day 8. Rituximab: 250 mg/m^2 IV over 4-6 Hours on Days 1 and 8 prior to the administration of 111In Zevalin and 90Y Zevalin, respectively.
Measure Participants	31
Male	0.62 2%
Female	0.89 2.9%

Adverse Events

Time Frame	Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Arm/Group Title	Zevalin
Arm/Group Description	Ibritumomab Tiuxetan (Zevalin): 111In Zevalin (5 mCi of ^111In, 1.6 mg of Ibritumomab Tiuxetan) intravenous (IV) over 10 minutes on Day 1; 90Y Zevalin 0.3 or 0.4 mCi/kg IV over 10 minutes on Day 8. Rituximab: 250 mg/m^2 IV over 4-6 Hours on Days 1 and 8 prior to the administration of 111In Zevalin and 90Y Zevalin, respectively.
All Cause Mortality
	Zevalin
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Zevalin
	Affected / at Risk (%)	# Events
Total	1/31 (3.2%)
Gastrointestinal disorders
PERFORATION, GI	1/31 (3.2%)	1
General disorders
DEATH	1/31 (3.2%)	1
Other (Not Including Serious) Adverse Events
	Zevalin
	Affected / at Risk (%)	# Events
Total	29/31 (93.5%)
Blood and lymphatic system disorders
LEUKOCYTOSIS	19/31 (61.3%)	19
Eye disorders
BLURRED VISION	4/31 (12.9%)	4
DRY EYE	1/31 (3.2%)	1
PROPTOSIS/Enophthalmos	1/31 (3.2%)	1
REDNESS OF EYES	2/31 (6.5%)	2
TINNITUS	1/31 (3.2%)	1
Gastrointestinal disorders
ABDOMEN PAIN	2/31 (6.5%)	2
ANOREXIA	1/31 (3.2%)	1
CONSTIPATION	4/31 (12.9%)	4
COUGH	1/31 (3.2%)	1
DIARRHEA	4/31 (12.9%)	4
HEARTBURN	1/31 (3.2%)	1
NAUSEA	8/31 (25.8%)	8
PAIN (ABDOMEN NOS)	1/31 (3.2%)	1
PERFORATION, GI	1/31 (3.2%)	1
VOMITING	3/31 (9.7%)	3
General disorders
EDEMA: HEAD AND NECK	1/31 (3.2%)	1
EDEMA: LIMB	4/31 (12.9%)	4
FATIGUE	19/31 (61.3%)	19
PAIN	1/31 (3.2%)	1
RIGORS/CHILLS	1/31 (3.2%)	1
SWEATING	3/31 (9.7%)	3
Immune system disorders
ALLERGIC REACTION	2/31 (6.5%)	2
ALLERGIC RHINITIS	1/31 (3.2%)	1
Infections and infestations
ABDOMINAL INFECTION	1/31 (3.2%)	1
BLADDER INFECTION	1/31 (3.2%)	1
INFECTION UNKNOWN	2/31 (6.5%)	2
INFECTION WITHOUT NEUTROPHIL INCREASE	2/31 (6.5%)	2
Injury, poisoning and procedural complications
BRUISING	1/31 (3.2%)	1
Investigations
FEVER WITHOUT NEUTROPHIL INCREASE	4/31 (12.9%)	4
HEMOGLOBIN INCREASE	12/31 (38.7%)	12
NEUTROPHILS CHANGE (Absolute neutrophil count (ANC))	21/31 (67.7%)	21
PLATELETS, DECREASE	21/31 (67.7%)	21
Musculoskeletal and connective tissue disorders
MUSCLE SPASM	1/31 (3.2%)	1
PAIN (BACK)	1/31 (3.2%)	1
PAIN (JOINT)	1/31 (3.2%)	1
PAIN (MUSCLE)	3/31 (9.7%)	3
Nervous system disorders
DIZZINESS	4/31 (12.9%)	4
HEADACHE	3/31 (9.7%)	3
NEUROPATHY: SENSOR	8/31 (25.8%)	8
PAIN (HEAD/HEADACHES)	2/31 (6.5%)	2
Psychiatric disorders
INSOMNIA	1/31 (3.2%)	1
Reproductive system and breast disorders
PAIN PELVIC	1/31 (3.2%)	1
VAGINAL BLEEDING	1/31 (3.2%)	1
Respiratory, thoracic and mediastinal disorders
DYSPNEA	2/31 (6.5%)	2
HEMORRHAGE, PULMONARY	1/31 (3.2%)	1
Skin and subcutaneous tissue disorders
PRURITUS	2/31 (6.5%)	2
RASH/DESQUAMATION	1/31 (3.2%)	1
Vascular disorders
THROMBOSIS/THROMBUS	1/31 (3.2%)	1

Limitations/Caveats

[Not Specified]

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.