Tositumomab and Iodine I 131 Tositumomab in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma in First Remission

• Sponsor: Fred Hutchinson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00476047
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 16
• Location: 1
• Arm: 1
• Duration (Months): 96
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This phase II trial studies how well tositumomab and iodine I 131 tositumomab works in treating patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) that have had their first decrease in or disappearance of signs and symptoms of cancer (first remission). Monoclonal antibodies, such as tositumomab and iodine I 131 tositumomab, may block cancer growth in different ways by targeting certain cells.

Condition or Disease	Intervention/Treatment	Phase
Lymphoid Leukemia in Remission; Stage I Chronic Lymphocytic Leukemia; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma	Combination Product: Tositumomab and Iodine I 131 Tositumomab	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To estimate the progression-free survival at 2 years following administration of 131I-tositumomab (tositumomab and iodine I 131 tositumomab) in patients with CLL/SLL who achieve a complete remission (CR) or partial remission (PR) with prior therapy.

2. To improve the response rate by administering 131I-tositumomab to patients who have achieved a PR not a CR after any prior therapy.

3. To eliminate residual disease (documented by flow cytometry or polymerase chain reaction [PCR]) using 131I-tositumomab in patients who have achieved a CR after any prior therapy.

SECONDARY OBJECTIVES:

1. To evaluate the toxicities of 131I-tositumomab in 1st remission patients with previously treated CLL/SLL.

OUTLINE:

Patients receive tositumomab and iodine I 131 tositumomab intravenously (IV) over 90 minutes on day 0 and then again 7-14 days later over 30-60 minutes.

After completion of study treatment, patients are followed up weekly for 3 months, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Study of 131I-Tositumomab (Bexxar®) Consolidation in Patients With B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma in First Remission
• Study Start Date: Feb 1, 2007
• Actual Primary Completion Date: Feb 1, 2015
• Actual Study Completion Date: Feb 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (monoclonal antibody therapy) Patients receive tositumomab and iodine I 131 tositumomab IV over 90 minutes on day 0 and then again 7-14 days later over 30-60 minutes.	Combination Product: Tositumomab and Iodine I 131 Tositumomab; Give IV; Other Names: Bexxar Bexxar Therapeutic Regimen Bexxar Therapy

Outcome Measures

Primary Outcome Measures

1. Probability of Progression-free Survival (PFS) [36 months]

   Progression free survival (PFS) is defined as the interval between the first treatment day to the first sign of disease progression. This outcome measures the percentage of participants with PFS at 36 months.

2. Improved Response Rate After Treatment With 131I-tositumomab for Patients Who Had Evidence of CLL at the End of Initial Chemotherapy [3 months after 131I-tositumomab consolidation]

   Response rates determined using National Cancer Institute (NCI) working group guidelines plus computed tomography (CT) scan criteria. Participants were assessed for response after initial chemotherapy and again 3 months after 131I-tositumomab treatment.Only patients who had less than a complete response (CR) after initial chemotherapy were assessed for improved response after 131I-tositumomab.

3. Minimal Residual Disease (MRD) by Flow Cytometry or Polymerase Chain Reaction (PCR) in Patients Who Had a Complete Remission (CR) After Any Prior Therapy [3 months after 131I-tositumomab consolidation]

Secondary Outcome Measures

1. Evaluate Toxicities of 131I-tositumomab [48 months (median)]

   Adverse events following treatment of 131I-tositumomab

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Patients with a diagnosis of cluster of differentiation (CD)20+ CLL/SLL; prior to the first treatment patients with CLL must have been either Rai stage III/IV disease or Rai stage I/II with evidence of disease activity as defined by the National Cancer Institute (NCI) 1996 guidelines, and patients with SLL must have been Stage III or IV per Ann Arbor staging system

• Patient has received prior therapy and is in 1st remission with a partial or complete response to treatment

• Patients must have no more than 25% of the intratrabecular marrow space involved by leukemia in bone marrow biopsy specimens as assessed microscopically after completion of treatment; bilateral posterior iliac crest core biopsies are required if the percentage of intratrabecular space involved exceeds 10% on a unilateral biopsy; the mean of bilateral biopsies must be no more than 25%

• Patient must have consented to participate in the study and signed and dated an appropriate institutional review board (IRB)-approved consent form that conforms to federal and institutional guidelines

• Patient must have a Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 (0 = fully active, able to carry on all pre-disease performance without restriction; 1 = restricted in physically strenuous activity but ambulatory and ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; 2 = ambulatory and capable of all self-care but unable to carry out any work activities and is up and about more than 50% of waking hours)

• Patient must have an anticipated survival of at least 3 months

• Granulocytes >= 1,500/uL within 14 days of planned dosimetric infusion

• Platelets >= 100,000/uL within 14 days of planned dosimetric infusion

• White blood count =< 20,000/mm^3

• Serum creatinine < 2 times upper limit of normal

• Total bilirubin < 2 times upper limit of normal

• Aspartate aminotransferase (AST) < 5 times upper limit of normal

• Males and females must agree to use a contraceptive method from enrollment to 6 months after receiving I-131 labeled tositumomab

Exclusion Criteria:

• Patients who have received prior radiolabeled antibody

• Patients with active hemolysis

• Patients must not require sustained transfusion support of blood products

• Patients in 2nd remission or beyond

• Patients who have undergone treatment with either stem cell or bone marrow transplant

• Patients with active obstructive hydronephrosis

• Patients with evidence of any significant systemic illness, active hepatitis B infection or other active infection at the time of study entry

• Patients with New York Heart Association class III or IV heart disease or other serious illness that would preclude evaluation

• Patients with known human immunodeficiency virus (HIV) infection

• Patients who are pregnant or nursing

• Patients with prior malignancy other than CLL/SLL, except for adequately treated skin cancer (basal cell or squamous cell carcinoma), in situ cervical cancer, or other cancer for which the patient has been disease-free for 5 years unless approved by the principal investigator (PI)

• Patients with active brain or leptomeningeal involvement by malignancy

• Patients who have, in the opinion of the investigator, other medical, social, or psychosocial factors that may negatively impact compliance or their safety by participation in this study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington	United States	98109

Sponsors and Collaborators

• Fred Hutchinson Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Mazyar Shadman, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mazyar Shadman, Principal Investigator, Fred Hutchinson Cancer Center
• ClinicalTrials.gov Identifier: NCT00476047
• Other Study ID Numbers: PSOC 2301; NCI-2011-01311; PSOC 2301; P30CA015704
• First Posted: May 21, 2007
• Last Update Posted: Oct 12, 2017
• Last Verified: Oct 1, 2017

• Additional relevant MeSH terms: Lymphoma; Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Tositumomab I-131

Study Results

Participant Flow

Arm/Group Title	Treatment (Monoclonal Antibody Therapy)
Arm/Group Description	Patients receive tositumomab and iodine I 131 tositumomab IV over 90 minutes on day 0 and then again 7-14 days later over 30-60 minutes. Tositumomab and Iodine I 131 Tositumomab: Give IV Laboratory Biomarker Analysis: Correlative studies
Period Title: Overall Study
STARTED	16
Completed Treatment	16
COMPLETED	15
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Treatment (Monoclonal Antibody Therapy)
Arm/Group Description	Patients receive tositumomab and iodine I 131 tositumomab IV over 90 minutes on day 0 and then again 7-14 days later over 30-60 minutes. Tositumomab and Iodine I 131 Tositumomab: Give IV Laboratory Biomarker Analysis: Correlative studies
Overall Participants	16
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	61
Sex: Female, Male (Count of Participants)
Female	5 31.3%
Male	11 68.8%
CLL or SLL (Count of Participants)
CLL (Chronic lymphocytic leukemia)	11 68.8%
SLL (Small lymphocytic leukemia)	5 31.3%
Prior chemotherapy (Count of Participants)
FR (fludaribine and rituximab)	9 56.3%
FCR(fludaribine, cyclophosphamide and rituximab)	4 25%
BR (bendamustine and rituximab)	2 12.5%
R-CHOP	1 6.3%
Disease status before 131 I-tositumomab (Count of Participants)
CR (complete response)	4 25%
PR (partial response)	12 75%
Minimal Residual Disease (MRD) status before 131 I-tositumomab (Count of Participants)
Positive	12 75%
Negative	4 25%

Outcome Measures

1. Primary Outcome

Title	Probability of Progression-free Survival (PFS)
Description	Progression free survival (PFS) is defined as the interval between the first treatment day to the first sign of disease progression. This outcome measures the percentage of participants with PFS at 36 months.
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Monoclonal Antibody Therapy)
Arm/Group Description	Patients receive tositumomab and iodine I 131 tositumomab IV over 90 minutes on day 0 and then again 7-14 days later over 30-60 minutes. Tositumomab and Iodine I 131 Tositumomab: Give IV Laboratory Biomarker Analysis: Correlative studies
Measure Participants	16
Number (95% Confidence Interval) [percentage probability]	52

2. Primary Outcome

Title	Improved Response Rate After Treatment With 131I-tositumomab for Patients Who Had Evidence of CLL at the End of Initial Chemotherapy
Description	Response rates determined using National Cancer Institute (NCI) working group guidelines plus computed tomography (CT) scan criteria. Participants were assessed for response after initial chemotherapy and again 3 months after 131I-tositumomab treatment.Only patients who had less than a complete response (CR) after initial chemotherapy were assessed for improved response after 131I-tositumomab.
Time Frame	3 months after 131I-tositumomab consolidation

Outcome Measure Data

Analysis Population Description

Participants who had a partial response (PR) after initial chemotherapy. Response assessed using NCI working group guidelines + CT criteria as described in the protocol.

Arm/Group Title	Treatment (Monoclonal Antibody Therapy)
Arm/Group Description	Patients receive tositumomab and iodine I 131 tositumomab IV over 90 minutes on day 0 and then again 7-14 days later over 30-60 minutes. Tositumomab and Iodine I 131 Tositumomab: Give IV
Measure Participants	12
Participants who achieved a CR	8 50%
Participants who did not achieve a CR	4 25%

3. Primary Outcome

Title	Minimal Residual Disease (MRD) by Flow Cytometry or Polymerase Chain Reaction (PCR) in Patients Who Had a Complete Remission (CR) After Any Prior Therapy
Time Frame	3 months after 131I-tositumomab consolidation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patient Who Achieved CR After Any Prior Therapy
Arm/Group Description	Patients who received study treatment and who had achieved a complete remission (CR) after any prior therapy.
Measure Participants	4
Negative MRD status	4 25%
Positive MRD status	0 0%

4. Secondary Outcome

Title	Evaluate Toxicities of 131I-tositumomab
Description	Adverse events following treatment of 131I-tositumomab
Time Frame	48 months (median)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Monoclonal Antibody Therapy)
Arm/Group Description	Patients receive tositumomab and iodine I 131 tositumomab IV over 90 minutes on day 0 and then again 7-14 days later over 30-60 minutes. Tositumomab and Iodine I 131 Tositumomab: Give IV Laboratory Biomarker Analysis: Correlative studies
Measure Participants	16
Grade 3 anemia	1 6.3%
Grade 3 or 4 neutropenia	13 81.3%
Grade 3 or 4 thrombocytopenia	8 50%
Hypogammaglobulinemia	1 6.3%
Neutropenia related sepsis/typhlitis	1 6.3%
Basal cell carcinoma	2 12.5%
Squamous cell carcinoma	1 6.3%
Myelodysplastic syndrome	2 12.5%

Adverse Events

Arm/Group Title	Treatment (Monoclonal Antibody Therapy)
Arm/Group Description	Patients receive tositumomab and iodine I 131 tositumomab IV over 90 minutes on day 0 and then again 7-14 days later over 30-60 minutes. Tositumomab and Iodine I 131 Tositumomab: Give IV Laboratory Biomarker Analysis: Correlative studies
All Cause Mortality
	Treatment (Monoclonal Antibody Therapy)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Monoclonal Antibody Therapy)
	Affected / at Risk (%)	# Events
Total	0/16 (0%)
Other (Not Including Serious) Adverse Events
	Treatment (Monoclonal Antibody Therapy)
	Affected / at Risk (%)	# Events
Total	16/16 (100%)
Blood and lymphatic system disorders
Anemia Grade 3	1/16 (6.3%)	1
Neutropenia Grade 3 or 4	13/16 (81.3%)	16
Thrombocytopenia Grade 3 or 4	8/16 (50%)	16

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.