Lymphoma, Non-Hodgkin
Conditions
Brief summary
The purpose of this study is to determine the effectiveness of fludarabine, Velcade, and rituximab treatment regimen in patients with relapsed or refractory follicular non-Hodgkin lymphoma.
Detailed description
OUTLINE: This is a multi-center study. * Fludarabine 25 mg/m2 IV over 30 minutes , Days 1, 2, 4 * Velcade(given after fludarabine) 1.3 mg/m2 IV push over 3 to 5 seconds, Days 1, 4, 8, 11 * Rituximab (given after Velcade) 375 mg/m2 IV piggyback, Day 1 * Cycle = 28 days; max 6 cycles ECOG Performance Status: 0-2 Life Expectancy: Not specified Hematopoietic: * Absolute neutrophil count (ANC) ≥ 1.5 K/mm3 (ANC \> 0.5 K/mm3 if known lymphomatous involvement of the bone marrow). * Platelets ≥ 100 K/mm3 (Platelets \>50 K/mm3 if known lymphomatous involvement of the bone marrow). Hepatic: * Total bilirubin ≤1.5 ULN * Aspartate aminotransferase (AST, SGOT) ≤ 2.5 x ULN * Alanine aminotransferase (ALT, SGPT) ≤ 2.5 x ULN Renal: * Creatinine \< 1.5 x institutional upper limit (ULN) or creatinine clearance ≥ 50 cc/min Cardiovascular: * No myocardial infarction within 6 months prior to enrollment * No heart failure per New York Heart Association Classification III or IV * No severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia
Interventions
DRUGFludarabine
Fludarabine 25 mg/m2 IV over 30 minutes on days 1, 2, 4. Cycle = 28 days; maximum of 6 cycles of therapy.
DRUGVelcade
Velcade (given after fludarabine)1.3 mg/m2 IV push over 3 to 5 seconds on days 1, 4, 8, 11. Cycle = 28 days; maximum of 6 cycles of therapy.
DRUGRituximab
Rituximab given after Velcade) 375 mg/m2 IV piggyback on day 1. Cycle = 28 days; maximum of 6 cycles of therapy.
Sponsors
Genentech, Inc.
Millennium Pharmaceuticals, Inc.
Hoosier Cancer Research Network
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
* Must have histologically confirmed Follicular Non-Hodgkin Lymphoma (Grade I, II, or IIIa) * Must have measurable disease defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded as ≥2 cm with conventional techniques or as \>1 cm with spiral CT scan) and obtained by imaging within 30 days prior to registration for protocol therapy. * Must have received at least one prior therapeutic regimen, but no more than three prior regimens of conventional cytotoxic therapy. NOTE: Prior recipients of stem cell transplantation will be included, with the preparative cytoreductive and high-dose therapies counted collectively as one prior therapy. * Must be off all cytotoxic chemotherapy for at least four weeks prior to registration for protocol therapy (6 weeks for BCNU or mitomycin C). * Patients are allowed to have received one course of prior radioimmunotherapy (RIT: either tositumomab or ibritumomab). NOTE: Radioimmunotherapy must be completed at least 12 weeks prior to registration for protocol therapy with recovery to baseline of ANC and platelets. * Prior fludarabine, Velcade or rituximab is allowed as long as therapy is completed at least 30 days prior to registration for protocol therapy. Patients may be refractory (defined as not responding or demonstrating progressive disease in \<6 months) to prior rituximab. Patients may not be refractory to prior fludarabine or Velcade. * Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed and for 30 days following protocol therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. * Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to prior to registration for protocol therapy. NOTE: Patients are considered of child bearing potential unless they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal (no menses for at least 12 months). * Females must not be breastfeeding. * Males must agree to use an acceptable method of contraception for the duration of the study.
Exclusion criteria
* No current active CNS metastases. Patients with neurological symptoms must undergo a head CT scan or brain MRI to exclude brain metastasis within 7 days prior to registration for protocol therapy. NOTE: Patients with treated brain metastasis must be off steroids or on tapering or stable doses of steroids and have completed radiation at least 30 days prior to registration for protocol therapy. * No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, Gleason ≤ grade 6 prostate cancers, or other cancer for which the subject has been disease-free for at least 3 years. * No treatment with any investigational agent within 30 days prior to registration for protocol therapy. * Prior radiation therapy is allowed to \< 25% of the bone marrow. NOTE: No radiation therapy within 30 days prior to registration for protocol therapy. * No clinically significant infections as judged by the treating investigator. * No active HIV, hepatitis B or hepatitic C infection. * No cerebrovascular accident (CVA) within 6 months of study enrollment. * No psychiatric illness/social situations that would limit compliance with study requirements. * No history of hypersensitivity to Velcade, boron or mannitol. * No peripheral neuropathy grade \> 1.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | 6 months | To determine the overall response rate and frequency of complete and partial responses in patients with relapsed or refractory follicular non-Hodgkin lymphoma (NHL) who receive therapy with fludarabine, Velcade, and rituximab administered every 28 days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Survival | 6 months | To evaluate the progression-free survival and event-free survival in patients who receive therapy with fludarabine, Velcade, and rituximab. |
| Toxicity | 6 months | To evaluate the toxicity profile of this regimen. Adverse event counts by grade are presented. |
| Biologic Interaction | 6 months | To explore the biologic interaction between fludarabine and Velcade and determine if Velcade can potentiate the DNA-damaging effect of fludarabine. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fludarabine, Velcade and Rituximab Fludarabine, Velcade and Rituximab
Fludarabine: Fludarabine 25 mg/m2 IV over 30 minutes on days 1, 2, 4. Cycle = 28 days; maximum of 6 cycles of therapy.
Velcade: Velcade (given after fludarabine)1.3 mg/m2 IV push over 3 to 5 seconds on days 1, 4, 8, 11. Cycle = 28 days; maximum of 6 cycles of therapy.
Rituximab: Rituximab given after Velcade) 375 mg/m2 IV piggyback on day 1. Cycle = 28 days; maximum of 6 cycles of therapy. | 4 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Fludarabine, Velcade and Rituximab |
|---|---|
| Age, Continuous | 59.50 years STANDARD_DEVIATION 14.01 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Region of Enrollment United States | 4 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 4 / 4 |
| serious Total, serious adverse events | 1 / 4 |
Outcome results
Primary
Overall Response Rate
To determine the overall response rate and frequency of complete and partial responses in patients with relapsed or refractory follicular non-Hodgkin lymphoma (NHL) who receive therapy with fludarabine, Velcade, and rituximab administered every 28 days.
Time frame: 6 months
Population: Data for this primary objective was not collected or analyzed due to the termination of the study.
Secondary
Biologic Interaction
To explore the biologic interaction between fludarabine and Velcade and determine if Velcade can potentiate the DNA-damaging effect of fludarabine.
Time frame: 6 months
Population: Data for this secondary objective was not collected or analyzed due to the termination of the study.
Secondary
Survival
To evaluate the progression-free survival and event-free survival in patients who receive therapy with fludarabine, Velcade, and rituximab.
Time frame: 6 months
Population: Data for this secondary objective was not collected or analyzed due to the termination of the study.
Secondary
Toxicity
To evaluate the toxicity profile of this regimen. Adverse event counts by grade are presented.
Time frame: 6 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fludarabine, Velcade and Rituximab | Toxicity | Total Adverse Events | 122 number of adverse events |
| Fludarabine, Velcade and Rituximab | Toxicity | Grade 1 Adverse Events | 77 number of adverse events |
| Fludarabine, Velcade and Rituximab | Toxicity | Grade 2 Adverse Events | 35 number of adverse events |
| Fludarabine, Velcade and Rituximab | Toxicity | Grade 3 Adverse Events | 9 number of adverse events |
| Fludarabine, Velcade and Rituximab | Toxicity | Grade 4 Adverse Events | 1 number of adverse events |
| Fludarabine, Velcade and Rituximab | Toxicity | Grade 5 Adverse Events | 0 number of adverse events |