A Phase I-II Study of Oxaliplatin, Fludarabine, Cytarabine and Rituximab in Patients With Richter's Transformation, Prolymphocytic Leukemia or Refractory/Relapsed B-Cell Chronic Lymphocytic Leukemia
Oxaliplatin, fludarabine, cytarabine and rituximab are anticancer drugs. Oxaliplatin is a
platinum compound that has been shown to be effective in fighting other cancers. Oxaliplatin
is a third generation platinum compound with higher activity and less toxicity in colon
cancer and other tumors compared to other platinum compounds, such as cisplatin. Oxaliplatin
has shown activity in patients with relapsed or refractory non-Hodgkin's lymphoma.
Before treatment starts, you will have a complete physical exam and routine blood tests
(about 2 teaspoons). A bone marrow sample will be collected. 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bone marrow is withdrawn through a large needle. Women who are able to have children must
have a negative blood or urine pregnancy test.
This research study has two parts, a Phase I part and a Phase II part. You will receive at
least 1 cycle of therapy.
Oxaliplatin will be given through a needle in your vein (called an IV) for 4 days (Days 1
through 4). Rituximab will be given through an IV on Day 3 of the first cycle and on Day 1
on every cycle after that. One day after the first dose of oxaliplatin and rituximab (Day
2), fludarabine and cytarabine will be given through an IV for two days (Days 2 and 3).
Peg-filgrastim will be given subcutaneously (through a needle just under your skin) on Day
6. Other IV fluids such as saline will be given on all of the treatment days to keep you
from being dehydrated, which means that the daily visit may take eight hours. The
combination will be repeated once a cycle (every 28 days) for up to a total of 6 cycles.
During the Phase I and II phases of the study, researchers will be testing different dose
levels of the study drug combination. Three patients will be enrolled at each dose level.
Each time the dose level is raised, it will occur after each patient has been monitored for
28 days. Individual patients who do not experience serious drug-related side effects after
the second cycle may receive the next higher dose level for the following treatment cycles.
Drugs will be given before each dose of rituximab to lower the risk of side effects. If
side effects do occur during rituximab treatment, rituximab may have to be stopped until the
side effects go away and then restarted. This may make your time in the outpatient area
The first treatment cycle will be given at M. D. Anderson. Depending on your response to
treatment, up to 5 more cycles can be performed either at M. D. Anderson or at home with
your regular physician. After 3 cycles of treatment, you will be checked at M. D.
Anderson to see if the disease is responding to treatment. If the disease is responding
after 3 cycles of therapy, you may continue to receive therapy for up to 3 more cycles. If
the disease is not responding, you will be taken off the study and your doctor will discuss
other treatment options with you.
Once the best safe dose of the drug combination is found in the Phase I portion of the
study, the next group of participants entering the study will take part in the Phase II
portion of the study. The goal of this part of the study is to look at the effects of the
drug combination in patients with refractory CLL, prolymphocytic leukemia or Richter's
transformation. The dose level for the combination will be the one found in the Phase I
part of the study.
The same dose levels for all four drugs will be used throughout the Phase II portion of the
study, unless intolerable side effects occur. In that case, the dose may be lowered or the
treatment may be stopped. You will be taken off study if the disease gets worse.
During each treatment cycle, you will have blood samples (about 1 teaspoon each) taken once
every 1-2 weeks. Bone marrow biopsies will be done at the end of the 3rd and 6th
After your last cycle of treatment is completed, you will have blood drawn (about 2
teaspoons each) every 3 months for as long as you are in remission, for routine testing.
This is an investigational study. The FDA has authorized the use of these drugs for
research only, when given for this purpose. All of these drugs are commercially available
for other types of treatment. Oxaliplatin will be free of charge during the study. You
and/or your insurance company will be responsible for the cost of the other drugs used in
this study. Patients will be enrolled at M. D. Anderson, University of California, San
Diego, or Dana-Farber Cancer Institute. Up to 52 patients will take part in this multicenter
study. The estimated number of patients who will be treated at M. D. Anderson is up to 52.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum Tolerated Dose (MTD) Oxaliplatin
MTD defined as dose level at which 2/3 or 2/6 participants experience Dose Limiting Toxicity (DLT), where DLTs are any oxaliplatin-related ≥Grade 3 non-hematological toxicity involving a major organ system (brain, heart, kidney, liver, lung) in the National Cancer Institute (NCI) Version 3.0 toxicity scale.
From treatment onset to end of each cycle of treatment (every 21 days)
William G. Wierda, MD, PhD
M.D. Anderson Cancer Center
United States: Food and Drug Administration
|Dana-Farber Cancer Institute||Boston, Massachusetts 02115|
|University of California-San Diego||La Jolla, California 92037-0698|