Non-Hodgkin's Lymphoma, Cancer
Conditions
Keywords
Non Hodgkin's Lymphoma, Phase II, Lymphoid malignancies
Brief summary
1.1 To determine the efficacy of a combination treatment of VP-16, chlorambucil, dexamethasone, and vincristine in patients with relapsed/refractory hematological malignancies. 1.2 To determine the toxicity profile of the above regimen in this patient population. 1.3 Evaluate the effect of low dose administration of chemotherapy on angiogenesis, and correlate this with tumor responses.
Detailed description
The purpose of the study is to see how effective the combination of chemotherapy drugs VP-16, chlorambucil, dexamethasone, and vincristine is for patients who have blood cancers that have returned or not responded to prior treatment. Some patients may also receive a medication called rituximab if their doctor thinks it is appropriate. This drug combination will be given to study participants in a low dose continuous basis. The study will also collect information about the side effects of the above drug combination on patients with these types of cancers. Previous studies on patients with non-Hodgkin's lymphoma indicate that some patients treated with this drug combination achieved a high response. The aim of this study is to test this drug combination in a controlled setting.
Interventions
DRUGVincristine
Vincristine should be administered intravenously through a freely-running IV.
DRUGVP-16
The VP-16 is optional for the first cycle if the patient has delays in obtaining the drug.
DRUGRituximab
The total amount of rituximab needed for a patient's entire infusions (one course) will be determined at study entry. A single dose of 375 mg/m2 will be based upon the patient's actual body surface area calculated during the baseline evaluation. The dose level of rituximab will not be adjusted. Patients will only receive rituximab if their tumors are CD20 positive CLL or NHL. Rituximab will only be administered to patients if they have previously had less than 8 doses. If a patient is treated with rituxan they should have at least 4 doses
DRUGDexamethasone
Dexamethasone will be administered at 200mg q 14 days. Dexamethasone should be administered over a 1 hour infusion.
DRUGLevofloxacin
Levofloxacin will be administered at 500 mg PO qd.
Sponsors
New Mexico Cancer Research Alliance
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
* All patients, 18 years of age or older, with Hodgkin's lymphoma, Non-Hodgkin lymphoma (NHL), multiple myeloma (MM), or chronic lymphocytic leukemia (CLL) are eligible. * Patients must have a life expectancy of at least 12 weeks. * Patients must have a Zubrod performance status of 0-2. * Patients must sign an informed consent. * Patients should have adequate bone marrow function defined by an absolute peripheral granulocyte count of \> 1,000 or cells/mm3 and platelet count \>50,000/mm3 and absence of a regular red blood cell or platelet transfusion requirement. * Patients should have adequate hepatic function with a total bilirubin \< 2 mg/dl and SGOT or SGPT \< two times the upper limit of normal, and adequate renal function as defined by a serum creatinine \< 2.0 x upper limit of normal. * Patients must have received at least two previous chemotherapy regimens for their disease. * Patients must have measurable disease (NHL) or evaluable disease (MM, CLL).
Exclusion criteria
* Patients with symptomatic brain metastases are excluded from this study. * Pregnant women or nursing mothers are not eligible for this trial. Patients of child bearing potential must use adequate contraception. * Patients may receive no other concurrent chemotherapy or radiation therapy during this trial. * Patients with severe medical problems such as uncontrolled diabetes mellitus or cardiovascular disease or active infections are not eligible for this trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR), the Sum of Complete and Partial Responses | Up to 6 months after first on-study treatment | Solid tumor response is per Response Evaluation Criteria in Solid Tumors (RECIST) (ver 1.0). For CLL: complete remission (CR) requires the following for\>=2 months 1) no symptoms attributable to CLL, 2) normal physical examination, 3) absolute lymphocyte count\<4,000/µL, 4) ANC\>1,500/µL, 5) platelets\>100,000/µL, 6) hemoglobin\>11 g/dL, 7) bone marrow lymphocytosis\<30%, 8) no nodules in bone marrow. Partial response (PR) requires the following for \>=2 months 1) decrease in previously enlarged nodes, spleen, and liver by \>=50%, 2) ANC\>=1,500/µL or platelets\>=100,000/µL, 3) hemoglobin\>=11 g/dL, 4) 50% improvement over pre-therapy reductions in hemoglobin and/or platelets. For MM, CR is no monoclonal protein (M-protein) in blood and urine and \<5% plasma cells in bone marrow on \>=2 determinations \>=6 wk apart & stable bone disease & calcium levels. PR is\>50% and \>90% decreases in serum & urine M-protein, respectively, on \>=2 occasions for \>=6 wk, stable bone disease & calcium. |
Secondary
| Measure | Time frame |
|---|---|
| Toxicity | End of 2 cycles (cycle = 28 days) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm 1 Combination Treatment VP-16 at 50 mg/day, orally for 14 days every 28 days; Chlorambucil at 0.1 mg/kg/day orally for 14 days every 28 days; Vincristine at 2 mg intravenously every 14 days; Dexamethasone at 200 mg intravenously every 24 days; Rituxan (rituximab) at 375 mg/m2 intravenously every 14 day; Levofloxacin at 500 mg orally daily; Diflucan at 200 mg orally daily
One cycle lasts 28 days. At least 2 but no more than 8 cycles will be administered to each patient | 17 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Arm 1 Combination Treatment |
|---|---|
| Age, Continuous | 56 years |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 14 / 16 |
| serious Total, serious adverse events | 5 / 16 |
Outcome results
Primary
Overall Response Rate (ORR), the Sum of Complete and Partial Responses
Solid tumor response is per Response Evaluation Criteria in Solid Tumors (RECIST) (ver 1.0). For CLL: complete remission (CR) requires the following for\>=2 months 1) no symptoms attributable to CLL, 2) normal physical examination, 3) absolute lymphocyte count\<4,000/µL, 4) ANC\>1,500/µL, 5) platelets\>100,000/µL, 6) hemoglobin\>11 g/dL, 7) bone marrow lymphocytosis\<30%, 8) no nodules in bone marrow. Partial response (PR) requires the following for \>=2 months 1) decrease in previously enlarged nodes, spleen, and liver by \>=50%, 2) ANC\>=1,500/µL or platelets\>=100,000/µL, 3) hemoglobin\>=11 g/dL, 4) 50% improvement over pre-therapy reductions in hemoglobin and/or platelets. For MM, CR is no monoclonal protein (M-protein) in blood and urine and \<5% plasma cells in bone marrow on \>=2 determinations \>=6 wk apart & stable bone disease & calcium levels. PR is\>50% and \>90% decreases in serum & urine M-protein, respectively, on \>=2 occasions for \>=6 wk, stable bone disease & calcium.
Time frame: Up to 6 months after first on-study treatment
Population: Trial was terminated due to low accrual; no data to report. An insufficient number of subjects were accrued to report data accurately.
Secondary
Toxicity
Time frame: End of 2 cycles (cycle = 28 days)
Population: Trial was terminated early due to low accrual; no data to report. Adverse event data for enrolled patients is reported in the adverse event results section.