Lymphoproliferative Disorder
Conditions
Keywords
post-transplant lymphoproliferative disorder
Brief summary
RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. Monoclonal antibodies, such as rituximab, can block cancer cell growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving bortezomib together with rituximab may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving bortezomib together with rituximab works in treating patients with post-transplant lymphoproliferative disorders.
Detailed description
OBJECTIVES: Primary * To estimate the overall (complete and partial) response rates in patients with CD20+ post-transplant lymphoproliferative disorders treated with bortezomib and rituximab. Secondary * To evaluate the duration of remission, time to treatment failure, relapse-free survival, and overall survival of these patients. * To characterize the quantitative and qualitative toxicities of this regimen. OUTLINE: * Induction therapy: Patients receive bortezomib intravenously (IV) and rituximab IV on days 1, 8, 15, and 22. Patients achieving complete remission (CR) after completion of induction therapy proceed to maintenance therapy after 6 months of rest. Patients achieving partial remission (PR) or stable disease after completion of induction therapy receive additional bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR/PR after completion of bortezomib therapy proceed to maintenance therapy after 3 months of rest. * Maintenance therapy: Patients receive bortezomib IV and rituximab IV on days 1, 8, 15, and 22. Treatment repeats every 6 months for 4 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for 2 years.
Interventions
BIOLOGICALrituximab
375 mg/m\^2 intravenously on Days 1,8, 15 and 22
DRUGbortezomib
1.3 mg/m\^2 intravenous bolus days 1, 8, 15 and 22
Sponsors
Millennium Pharmaceuticals, Inc.
Masonic Cancer Center, University of Minnesota
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
No
Inclusion criteria
* Histologically confirmed CD20+ B-cell post-transplant lymphoproliferative disorder * Has undergone prior solid organ transplant * Measurable disease as defined by Non-Hodgkin Lymphoma Response Criteria * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Absolute neutrophil count (ANC) ≥ 1,000/mm³ * Platelet count ≥ 75,000/mm³ * Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 40 mL/min * Alanine transaminase (ALT) and Aspartate aminotransferase (AST) ≤ 3 times upper limit of normal * Total bilirubin ≤ 2.0 mg/dL
Exclusion criteria
* Pregnant or nursing * Fertile patients must use effective contraception during and for 3 months after completion of study treatment * Peripheral neuropathy ≥ grade 2 * Known lymphomatous meningitis or central nervous system (CNS) involvement * HIV infection * Uncontrolled infection * Myocardial infarction within the past 6 months or uncontrolled angina * New York Heart Association class III-IV heart failure * Severe uncontrolled ventricular arrhythmias * Evidence of acute ischemia or active conduction system abnormalities by electrocardiogram (EKG) * Concurrent serious medical or psychiatric disorder (e.g., active infection or uncontrolled diabetes) that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient's ability to complete the study * Diagnosis or treatment for another malignancy within the past 3 years, except completely resected basal cell carcinoma or squamous cell carcinoma of the skin, in situ malignancy, or curatively treated low-risk prostate cancer * Known hypersensitivity to rituximab, bortezomib, boron, or any of the other agents used in this study * Less than 14 days since prior investigational drugs * Less than 4 weeks since prior bortezomib therapy (12 weeks for rituximab) and recovered from toxic effects prior to enrollment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Patients With Overall (Complete and Partial) Response Rates | Day 1 to 2 Years Post Treatment |
Secondary
| Measure | Time frame |
|---|---|
| Remission Duration Among Patients Who Respond to Treatment | Day 1 to 8 Months Post Treatment |
| Time to Treatment Failure | Day 1 to Time of Disease Progression |
| Relapse-free Survival | at 2 years |
| Overall Survival | at 2 years |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treated Study Participants Study participants receiving bortezomib and rituximab for post-transplant lymphoproliferative disorders (PTLD).
Induction Therapy:
rituximab: 375 mg/m\^2 intravenously on Days 1,8, 15 and 22 bortezomib: 1.3 mg/m\^2 intravenous bolus days 1, 8, 15 and 22 If complete response, start Maintenance Therapy. If partial response or stable disease, start Single Agent Bortezomib. If progressive disease, discontinue study treatment.
Single Agent Bortezomib bortezomib: 1.3 mg/m\^2 intravenous bolus days 1, 4, 8, 11 every 21 days for 4 cycles.
If complete response or partial response, start Maintenance Therapy. If stable disease or progressive disease, discontinue study treatment.
Maintenance Therapy:
rituximab: 375 mg/m\^2 intravenously on Days 1,8, 15 and 22 bortezomib: 1.3 mg/m\^2 intravenous bolus days 1, 8, 15 and 22 Repeat every 6 months for a total of 4 cycles. | 3 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Maintenance Therapy | concurrent illness | 1 |
Baseline characteristics
| Characteristic | Treated Study Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 3 / 3 |
| serious Total, serious adverse events | 2 / 3 |
Outcome results
Primary
Number of Patients With Overall (Complete and Partial) Response Rates
Time frame: Day 1 to 2 Years Post Treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treated Study Participants | Number of Patients With Overall (Complete and Partial) Response Rates | 2 participants |
Secondary
Overall Survival
Time frame: at 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treated Study Participants | Overall Survival | 1 participants |
Secondary
Relapse-free Survival
Time frame: at 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treated Study Participants | Relapse-free Survival | 2 participants |
Secondary
Remission Duration Among Patients Who Respond to Treatment
Time frame: Day 1 to 8 Months Post Treatment
Population: Both of the participants who responded to treatment were in remission at last contact or death.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treated Study Participants | Remission Duration Among Patients Who Respond to Treatment | 45 months |
Secondary
Time to Treatment Failure
Time frame: Day 1 to Time of Disease Progression
Population: Two participants had a complete response at the time they completed the study and were not included in this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treated Study Participants | Time to Treatment Failure | 1 months |