Study: Treatment of Relapsed Lymphoid Malignancies With an Anti-Angiogenic Approach
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm 1 Combination Treatment Treatment with combination therapy as follows: 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 At least 2 courses, but no more than 8 courses total, will be administered to each patient |
Drug: Vincristine
Vincristine should be administered intravenously through a freely-running IV.
Other Names:
Drug: VP-16
The VP-16 is optional for the first cycle if the patient has delays in obtaining the drug.
Other Names:
Drug: Rituximab
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
Other Names:
Drug: Dexamethasone
Dexamethasone will be administered at 200mg q 14 days. Dexamethasone should be administered over a 1 hour infusion.
Other Names:
Drug: Levofloxacin
Levofloxacin will be administered at 500 mg PO qd.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- Toxicity [End of 2 cycles (cycle = 28 days)]
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of New Mexico Cancer Center | Albuquerque | New Mexico | United States | 87131 |
Sponsors and Collaborators
- New Mexico Cancer Care Alliance
Investigators
- Principal Investigator: Dulcinea Quintana, MD, UNM Cancer Center
- Study Chair: Robert Hromas, MD, University of Florida
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- INST 1003C
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Arm 1 Combination Treatment |
|---|---|
| Arm/Group Description | 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 |
| Period Title: Overall Study | |
| STARTED | 17 |
| Received Treatment | 16 |
| COMPLETED | 14 |
| NOT COMPLETED | 3 |
Baseline Characteristics
| Arm/Group Title | Arm 1 Combination Treatment |
|---|---|
| Arm/Group Description | 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 |
| Overall Participants | 17 |
| Age (years) [Median (Full Range) ] | |
| Median (Full Range) [years] |
56
|
| Sex: Female, Male (Count of Participants) | |
| Female |
5
29.4%
|
| Male |
12
70.6%
|
Outcome Measures
| Title | Overall Response Rate (ORR), the Sum of Complete and Partial Responses |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Trial was terminated due to low accrual; no data to report. An insufficient number of subjects were accrued to report data accurately. |
| Arm/Group Title | Arm 1 Combination Treatment |
|---|---|
| Arm/Group Description | 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 |
| Measure Participants | 0 |
| Title | Toxicity |
|---|---|
| Description | |
| Time Frame | End of 2 cycles (cycle = 28 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Arm 1 Combination Treatment |
|---|---|
| Arm/Group Description | 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 |
| Measure Participants | 0 |
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Arm 1 Combination Treatment | |
| Arm/Group Description | VP-16 50mg/d PO x14 days q 28 days + Chlorambucil 0.1mg/kg/d PO x14 days q 28 days + Vincristine 2mg IV x14 days + Dexamethasone 200mg IV q 24 days + Rituxan (rituximab) 375 mg/m2 IVI x14 days + Levofloxacin 500 mg PO qd + Diflucan 200 mg PO qd Vincristine: should be administered intravenously through a freely-running IV at 2mg q 14 days. VP-16: The VP-16 is optional for the first cycle if the patient has delays in obtaining the drug. Dose and schedule 50 mg/d P.O. x14 days q 28 days. Rituximab: 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. Dexamethasone: Dexamethasone will be administered at 200mg q 14 days. Dexamethasone should be administered over a 1 hour infusion. Levofloxacin: Levofloxacin will be administ | |
All Cause Mortality |
||
| Arm 1 Combination Treatment | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Arm 1 Combination Treatment | ||
| Affected / at Risk (%) | # Events | |
| Total | 5/16 (31.3%) | |
| Blood and lymphatic system disorders | ||
| Neutrophil count decreased | 1/16 (6.3%) | 2 |
| Cardiac disorders | ||
| Arrhythmia (irregular heartbeat) | 1/16 (6.3%) | 1 |
| Gastrointestinal disorders | ||
| Dehydration | 1/16 (6.3%) | 2 |
| Diarrhea | 1/16 (6.3%) | 2 |
| General disorders | ||
| Death | 1/16 (6.3%) | 1 |
| Infections and infestations | ||
| Pneumonia | 1/16 (6.3%) | 1 |
| Metabolism and nutrition disorders | ||
| Hyperglycemia (high blood sugar) | 1/16 (6.3%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||
| Pneumonitis | 2/16 (12.5%) | 2 |
Other (Not Including Serious) Adverse Events |
||
| Arm 1 Combination Treatment | ||
| Affected / at Risk (%) | # Events | |
| Total | 14/16 (87.5%) | |
| Blood and lymphatic system disorders | ||
| Hemoglobin decreased | 8/16 (50%) | 20 |
| Leukocytes decreased | 5/16 (31.3%) | 23 |
| Neutrophils decreased | 7/16 (43.8%) | 28 |
| Platelet count decreased | 5/16 (31.3%) | 10 |
| Cardiac disorders | ||
| Hypotension (low blood pressure) | 1/16 (6.3%) | 1 |
| Ear and labyrinth disorders | ||
| Tinnitus (ringing in the ears) | 1/16 (6.3%) | 1 |
| Eye disorders | ||
| Dry eye | 1/16 (6.3%) | 1 |
| Extraocular muscle disorder | 1/16 (6.3%) | 1 |
| Blurred vision | 1/16 (6.3%) | 3 |
| Gastrointestinal disorders | ||
| Anorexia (Loss of appetite) | 3/16 (18.8%) | 3 |
| Constipation | 6/16 (37.5%) | 7 |
| Diarrhea | 2/16 (12.5%) | 4 |
| Dry mouth | 1/16 (6.3%) | 1 |
| Taste disturbance | 1/16 (6.3%) | 1 |
| Nausea | 8/16 (50%) | 8 |
| Vomiting | 1/16 (6.3%) | 1 |
| Gastrointestinal - Other | 2/16 (12.5%) | 2 |
| Rectal hemorrhage | 2/16 (12.5%) | 2 |
| General disorders | ||
| Fatigue | 11/16 (68.8%) | 14 |
| Fever | 3/16 (18.8%) | 3 |
| Rigors (stiffness) | 1/16 (6.3%) | 1 |
| Increased sweating | 1/16 (6.3%) | 1 |
| Weight loss | 1/16 (6.3%) | 1 |
| Epistaxis (Nosebleed) | 1/16 (6.3%) | 1 |
| Edema: limbs | 1/16 (6.3%) | 1 |
| Abdominal pain | 5/16 (31.3%) | 6 |
| Chest pain | 1/16 (6.3%) | 1 |
| Pain - Other | 1/16 (6.3%) | 2 |
| Scrotal pain | 1/16 (6.3%) | 1 |
| Immune system disorders | ||
| Allergic rhinitis (runny nose) | 1/16 (6.3%) | 1 |
| Infections and infestations | ||
| Pneumonia | 1/16 (6.3%) | 1 |
| Bladder infection | 1/16 (6.3%) | 1 |
| Investigations | ||
| Hypercalcemia (High calcium levels) | 1/16 (6.3%) | 2 |
| Hyperglycemia (High blood glucose) | 2/16 (12.5%) | 3 |
| Hyperuricemia (High uric acid) | 1/16 (6.3%) | 3 |
| Hypoalbuminemia (Low albumin levels) | 1/16 (6.3%) | 1 |
| Hypocalcemia (Low calcium levels) | 1/16 (6.3%) | 1 |
| Hypokalemia (Low potassium levels) | 5/16 (31.3%) | 6 |
| Hypomagnesemia (Low magnesium levels) | 1/16 (6.3%) | 4 |
| Blood creatinine increased | 1/16 (6.3%) | 1 |
| Musculoskeletal and connective tissue disorders | ||
| Musculoskeletal/Soft Tissue - Other | 1/16 (6.3%) | 1 |
| Osteoporosis | 1/16 (6.3%) | 1 |
| Back pain | 1/16 (6.3%) | 1 |
| Bone pain | 2/16 (12.5%) | 3 |
| Myalgia (Muscle pain) | 3/16 (18.8%) | 3 |
| Nervous system disorders | ||
| Agitation | 2/16 (12.5%) | 3 |
| Anxiety | 2/16 (12.5%) | 3 |
| Ataxia (Lack of muscle coordination) | 1/16 (6.3%) | 1 |
| Confusional state | 2/16 (12.5%) | 2 |
| Convulsions | 1/16 (6.3%) | 1 |
| Depression | 1/16 (6.3%) | 1 |
| Dizziness | 4/16 (25%) | 4 |
| Headache | 1/16 (6.3%) | 1 |
| Insomnia | 3/16 (18.8%) | 3 |
| Neurology - Other | 1/16 (6.3%) | 1 |
| Neuralgia (Nerve pain) | 1/16 (6.3%) | 17 |
| Peripheral sensory neuropathy | 7/16 (43.8%) | 10 |
| Renal and urinary disorders | ||
| Ureteric obstruction | 1/16 (6.3%) | 1 |
| Reproductive system and breast disorders | ||
| Decreased libido | 1/16 (6.3%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||
| Cough | 4/16 (25%) | 6 |
| Dyspnea (Shortness of breath) | 1/16 (6.3%) | 1 |
| Hiccups | 1/16 (6.3%) | 2 |
| Pulmonary/Upper Respiratory - Other | 2/16 (12.5%) | 2 |
| Skin and subcutaneous tissue disorders | ||
| Alopecia (Hair loss) | 4/16 (25%) | 4 |
| Exfoliative dermatitis | 2/16 (12.5%) | 2 |
Limitations/Caveats
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.
Results Point of Contact
| Name/Title | Dulcinea Quintana, MD |
|---|---|
| Organization | University of New Mexico |
| Phone | 505-272-4661 |
| dcandelaria@salud.unm.edu |
- INST 1003C