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
Conditions
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.
Detailed description
PRIMARY OBJECTIVES: I. 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. II. To improve the response rate by administering 131I-tositumomab to patients who have achieved a PR not a CR after any prior therapy. III. 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: I. 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.
Interventions
COMBINATION_PRODUCTTositumomab and Iodine I 131 Tositumomab
Give IV
Sponsors
National Cancer Institute (NCI)
Fred Hutchinson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| Evaluate Toxicities of 131I-tositumomab | 48 months (median) | Adverse events following treatment of 131I-tositumomab |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Tositumomab and Iodine I 131 Tositumomab: Give IV
Laboratory Biomarker Analysis: Correlative studies | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Treatment (Monoclonal Antibody Therapy) |
|---|---|
| Age, Continuous | 61 years |
| CLL or SLL CLL (Chronic lymphocytic leukemia) | 11 Participants |
| CLL or SLL SLL (Small lymphocytic leukemia) | 5 Participants |
| Disease status before 131 I-tositumomab CR (complete response) | 4 Participants |
| Disease status before 131 I-tositumomab PR (partial response) | 12 Participants |
| Minimal Residual Disease (MRD) status before 131 I-tositumomab Negative | 4 Participants |
| Minimal Residual Disease (MRD) status before 131 I-tositumomab Positive | 12 Participants |
| Prior chemotherapy BR (bendamustine and rituximab) | 2 Participants |
| Prior chemotherapy FCR(fludaribine, cyclophosphamide and rituximab) | 4 Participants |
| Prior chemotherapy FR (fludaribine and rituximab) | 9 Participants |
| Prior chemotherapy R-CHOP | 1 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 16 / 16 |
| serious Total, serious adverse events | 0 / 16 |
Outcome results
Primary
Improved Response Rate After Treatment With 131I-tositumomab for Patients Who Had Evidence of CLL at the End of Initial Chemotherapy
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
Population: 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 | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Monoclonal Antibody Therapy) | Improved Response Rate After Treatment With 131I-tositumomab for Patients Who Had Evidence of CLL at the End of Initial Chemotherapy | Participants who achieved a CR | 8 Participants |
| Treatment (Monoclonal Antibody Therapy) | Improved Response Rate After Treatment With 131I-tositumomab for Patients Who Had Evidence of CLL at the End of Initial Chemotherapy | Participants who did not achieve a CR | 4 Participants |
Primary
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
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Monoclonal Antibody Therapy) | Minimal Residual Disease (MRD) by Flow Cytometry or Polymerase Chain Reaction (PCR) in Patients Who Had a Complete Remission (CR) After Any Prior Therapy | Negative MRD status | 4 Participants |
| Treatment (Monoclonal Antibody Therapy) | Minimal Residual Disease (MRD) by Flow Cytometry or Polymerase Chain Reaction (PCR) in Patients Who Had a Complete Remission (CR) After Any Prior Therapy | Positive MRD status | 0 Participants |
Primary
Probability of Progression-free Survival (PFS)
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Monoclonal Antibody Therapy) | Probability of Progression-free Survival (PFS) | 52 percentage probability |
Secondary
Evaluate Toxicities of 131I-tositumomab
Adverse events following treatment of 131I-tositumomab
Time frame: 48 months (median)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (Monoclonal Antibody Therapy) | Evaluate Toxicities of 131I-tositumomab | Grade 3 anemia | 1 participants with this toxicity |
| Treatment (Monoclonal Antibody Therapy) | Evaluate Toxicities of 131I-tositumomab | Grade 3 or 4 neutropenia | 13 participants with this toxicity |
| Treatment (Monoclonal Antibody Therapy) | Evaluate Toxicities of 131I-tositumomab | Grade 3 or 4 thrombocytopenia | 8 participants with this toxicity |
| Treatment (Monoclonal Antibody Therapy) | Evaluate Toxicities of 131I-tositumomab | Hypogammaglobulinemia | 1 participants with this toxicity |
| Treatment (Monoclonal Antibody Therapy) | Evaluate Toxicities of 131I-tositumomab | Neutropenia related sepsis/typhlitis | 1 participants with this toxicity |
| Treatment (Monoclonal Antibody Therapy) | Evaluate Toxicities of 131I-tositumomab | Basal cell carcinoma | 2 participants with this toxicity |
| Treatment (Monoclonal Antibody Therapy) | Evaluate Toxicities of 131I-tositumomab | Squamous cell carcinoma | 1 participants with this toxicity |
| Treatment (Monoclonal Antibody Therapy) | Evaluate Toxicities of 131I-tositumomab | Myelodysplastic syndrome | 2 participants with this toxicity |