A Phase II Study of Avastin Plus Rituximab for Patients With Relapsed and Chemotherapy- or Rituxan-Refractory Aggressive B-Cell Non-Hodgkin's Lymphoma
18 Years
N/A
Both
Lymphoma
Trial Information
A Phase II Study of Avastin Plus Rituximab for Patients With Relapsed and Chemotherapy- or Rituxan-Refractory Aggressive B-Cell Non-Hodgkin's Lymphoma
Bevacizumab is a new research drug that may help to stop or slow the growth of blood vessels
in your tumor. These blood vessels are needed by the tumor to grow. Rituxan is a
commercially available drug that is commonly used to treat relapsed and refractory lymphoma.
Before treatment starts, you will be asked questions about your medical history and about
any surgeries you have had. You will have a complete physical exam including blood (around
3 tablespoons) and urine tests. You will have a sample of bone marrow collected to learn if
the lymphoma has spread to the bone marrow. To collect a bone marrow sample, an area of the
hip or chest bone is numbed with anesthetic and a small amount of bone marrow is withdrawn
through a large needle. You will have either a CT scan or a MRI of the neck, chest,
abdomen, and pelvis, and you will have a gallium or PET scan. You will be asked about any
medications that you are taking, including over-the-counter medications. Women who are able
to have children must have a negative blood pregnancy test.
Additional blood samples (2 tablespoons) will be collected from you before starting therapy
and every 2 months during this study for tests to help your doctors and researchers to learn
more about how Bevacizumab works.
During the study, you will be given a dose of rituximab by vein once a week for 8 weeks in a
row, and a dose of Bevacizumab every other week. The drugs will be contained in a bag and
will be given to you through a needle in one of your veins. This method of giving the drugs
is called an infusion. The infusion of Bevacizumab may take 1 to 2 hours, and the infusion
of rituximab may take up to 3 to 6 hours. This method of giving a drug is called an
infusion. In the first week, infusions of rituxan and Bevacizumab will be given on the same
day.
During the infusion of each drug, you will have your vital signs checked often and you will
be watched for any side effects. If you experience side effects, the infusion may be slowed
down or stopped until the symptoms have gone away.
Within 2 weeks after your 8th dose of rituximab, (4th dose of Bevacizumab) you will have a
follow-up visit scheduled to evaluate the status of the disease. During the follow-up
visit, you will have a physical exam and blood (around 4 tablespoons) will be collected for
lab tests. You will have a CT scan or a MRI, gallium or PET scan, and bone marrow biopsy
(if needed). If the disease gets worse or you experience any intolerable side effects, you
will be taken off the study. If you are taken off the study or your doctor decides that you
should stop study treatment, you will be asked to return to M. D. Anderson for all of the
scheduled follow-up visits to check for long term side effects of the drug and to check on
the status of the disease.
If the disease remains stable or shrinks after 8 weeks of therapy, you may continue to
receive Bevacizumab treatments every 2 weeks for a maximum of a total of 6 months. Even if
the treatment is shown to be of benefit to you, your doctor may not continue to give you
additional treatments with Bevacizumab beyond the total of 6 months.
After treatment, you will have follow-up visits scheduled to check on the status of the
disease. These visits will be scheduled every 3 months for 1 year, then every 4 months for
1 more year, then every 6 months until the disease gets worse. During these visits, you
will have a physical exam, blood tests (around 2 tablespoons), and either a CT scan or a
MRI. You will also have a sample of bone marrow collected.
This is an investigational study. Bevacizumab has been authorized by the FDA for use in
research only. Rituximab is FDA approved and is commercially available. There will be no
cost for Bevacizumab or for any tests and procedures that are not considered part of
standard of care. Up to 40 patients will take part in this study. All patients will be
enrolled at M. D. Anderson.
Inclusion Criteria:
- Must have bi-dimensionally measurable, recurrent or chemotherapy - or
Rituxan-refractory aggressive B-cell NHL (Diffuse large B-cell, transformed B-cell
lymphoma, or Mantle cell lymphoma)
- Patient who relapse after autologous (not allogeneic) stem cell transplantation are
eligible.
- Patients must have had prior Rituximab therapy, with response duration of at least 6
months to the last Rituximab-based therapy (single agent or in combination)
- No anti-lymphoma therapy within the past 3 weeks, and no radiation therapy within 2
weeks.
- Patients must not be eligible for treatment of a higher priority.
- Must have a good performance status (<3 Zubrod, >/=60 Karnofsky).
- Must have a good marrow reserve: ANC >/=1,000, Platelets >/=75,000.
- Bilirubin
- Age > 18 (There is no information about the toxicity of Bevacizumab especially
adverse effects on growth and development in pediatric patients).
- Must sign a consent form.
- Must have a life expectancy of > 12 weeks.
Exclusion Criteria:
- HIV positive
- History of serious cardiac disease such as myocardial infarction within 6 months of
treatment, brady- or tachyarrhythmia, or clinically uncontrolled hypertension (blood
pressure >160/110 mmHg).
- Active infection or history of opportunistic infection.
- Pregnant women or breast-feeding women.
- Women of child-bearing age who are not practicing adequate contraception.
- History of prior DVT or pulmonary embolus.
- INR > 1.5
- Serum creatinine > 2mg/dl, or clinically significant proteinuria (patients with >1+
proteinuria should have 24 hour urine collection and those with >2gm/day should be
excluded).
- Evidence of bleeding diathesis or coagulopathy.
- History of other cancers within 5 years except for basal cell carcinoma of the skin.
- Radiotherapy within 14 days of Day 0.
- Current, recent (within 21 days of Day 0), or planned participation in an
experimental drug study.
- Hemoglobin <9gm/dl (may be transfused or receive epoetin alfa [e.g., Epogen]to
maintain or exceed this level).
- History of other disease, metabolic dysfunction, physical examination finding, or
clinical laboratory finding giving reasonable suspicion of a disease or condition
that contraindicates the use of an investigational drug or that might affect the
interpretation of the results of the study or render the subject at high risk from
treatment complications.
- Serious, non-healing wound, ulcer, or bone fracture.
- History of CNS disease (including CNS involvement from primary cancer) or hemorrhagic
or thrombotic stroke within the last 6 months.
- History of hemoptysis requiring transfusion and/or hospitalization within the last 5
years.
- Anatomic lesion that increase the risk of serious hemorrhage (e.g., invasion of a
major vessel by tumor).
- Current, ongoing treatment with full-dose warfarin or its equivalent.
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to Day 0.
- Fine needle aspirations, indwelling catheter placement, or core biopsy within 7 days
prior to Day 0.
- Anticipation of need for major surgical procedure during the course of the study.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Number of Participants With Response (Complete Response or Progressive Disease)
Outcome Description:
Response criteria according to the International Working Group Recommendations for lymphoma where Complete Response (CR) defined as "complete disappearance" of clinically detectable disease and Progressive Disease defined by disease appearance by complete blood count (CBC), clinical and radiologic findings, and/or sizes of lymph nodes, spleen, and liver. Response measured from first documentation of response to first detection of progression.
Outcome Time Frame:
After 8 weeks of therapy (4 doses of Avastin and 8 doses of Rituximab),
Safety Issue:
No
Principal Investigator
Barbara Pro, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
M.D. Anderson Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
2003-0520
NCT ID:
NCT00081861
Start Date:
March 2004
Completion Date:
September 2007
Related Keywords:
- Lymphoma
- Non-Hodgkin's Lymphoma
- B-Cell Lymphoma
- Lymphoma
- Avastin
- Bevacizumab
- Rituximab
- Rituxan
- Lymphoma
- Lymphoma, Non-Hodgkin
- Lymphoma, B-Cell
Name | Location |
|---|---|
| UT MD Anderson Cancer Center | Houston, Texas 77030 |
