BOX WARNING WARNING
FLUDARA FOR INJECTION should be administered under the supervision of a qualified physician experienced in the use of antineoplastic therapy. FLUDARA FOR INJECTION can severely suppress bone marrow function. When used at high doses in dose-ranging studies in patients with acute leukemia, FLUDARA FOR INJECTION was associated with severe neurologic effects, including blindness, coma, and death. This severe central nervous system toxicity occurred in 36% of patients treated with doses approximately four times greater (96 mg/m2/day for 5-7 days) than the recommended dose. Similar severe central nervous system toxicity, including coma, seizures, agitation and confusion, has been reported in patients treated at doses in the range of the dose recommended for chronic lymphocytic leukemia.
Instances of life-threatening and sometimes fatal autoimmune phenomena such as hemolytic anemia, autoimmune thrombocytopenia/thrombocytopenic purpura (ITP), Evan's syndrome, and acquired hemophilia have been reported to occur after one or more cycles of treatment with FLUDARA FOR INJECTION. Patients undergoing treatment with FLUDARA FOR INJECTION should be evaluated and closely monitored for hemolysis.
In a clinical investigation using FLUDARA FOR INJECTION in combination with pentostatin (deoxycoformycin) for the treatment of refractory chronic lymphocytic leukemia (CLL), there was an unacceptably high incidence of fatal pulmonary toxicity. Therefore, the use of FLUDARA FOR INJECTION in combination with pentostatin is not recommended.
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FLUDARA SUMMARY
FLUDARA FOR INJECTION contains fludarabine phosphate, a fluorinated nucleotide analog of the antiviral agent vidarabine, 9-(beta)-D-arabinofuranosyladenine (ara-A) that is relatively resistant to deamination by adenosine deaminase. Each vial of sterile lyophilized solid cake contains 50 mg of the active ingredient fludarabine phosphate, 50 mg of mannitol, and sodium hydroxide to adjust pH to 7.7. The pH range for the final product is 7.2-8.2. Reconstitution with 2 mL of Sterile Water for Injection USP results in a solution containing 25 mg/mL of fludarabine phosphate intended for intravenous administration.
FLUDARA FOR INJECTION is indicated for the treatment of adult patients with B-cell chronic lymphocytic leukemia (CLL) who have not responded to or whose disease has progressed during treatment with at least one standard alkylating-agent containing regimen. The safety and effectiveness of FLUDARA FOR INJECTION in previously untreated or non-refractory patients with CLL have not been established.
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NEWS HIGHLIGHTSMedia Articles Related to Fludara (Fludarabine)
Genentech And Biogen Idec Receive A Complete Response From The FDA For Rituxan For Chronic Lymphocytic Leukemia
Source: Blood / Hematology News From Medical News Today [2009.11.19]
Genentech, Inc., a wholly-owned member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), and Biogen Idec (Nasdaq: BIIB) announced today that the U.S. Food and Drug Administration (FDA) issued a complete response on the companies' applications for Rituxan® (rituximab) plus fludarabine and cyclophosphamide (FC) for the treatment of people with previously untreated and previously treated chronic lymphocytic leukemia (CLL).
Published Studies Related to Fludara (Fludarabine)
Fludarabine, cyclophosphamide and rituximab for chronic lymphocytic leukemia: no country for old men? [2009.03]
The combination of fludarabine, cyclophosphamide and rituximab is regarded as the gold-standard treatment for chronic lymphocytic leukemia in many parts of the world, although rituximab has not yet been licensed for this use... At least half of patients with chronic lymphocytic leukemia are over 70 years of age and this regimen might be too toxic for such individuals.
Toxicity of fludarabine and cyclophosphamide with or without rituximab as initial therapy for patients with previously untreated mantle cell lymphoma: results of a randomised phase II study. [2009.02]
The National Cancer Research Network (NCRN) is currently coordinating a Phase III randomised study (LY05) comparing fludarabine and cyclophosphamide (FC) with or without rituximab (R) for previously untreated mantle cell lymphoma (MCL). The combination of FC is well-recognised as significantly immunosuppressive and there are concerns that adding rituximab may increase infection risk further...
Fludarabine, cyclophosphamide and rituximab for chronic lymphocytic leukemia: no country for old men? [2009.01.20]
The combination of fludarabine, cyclophosphamide and rituximab is regarded as the gold-standard treatment for chronic lymphocytic leukemia in many parts of the world, although rituximab has not yet been licensed for this use... At least half of patients with chronic lymphocytic leukemia are over 70 years of age and this regimen might be too toxic for such individuals.
Randomized phase III trial of fludarabine plus cyclophosphamide with or without oblimersen sodium (Bcl-2 antisense) in patients with relapsed or refractory chronic lymphocytic leukemia. [2007.03.20]
PURPOSE: Expression of Bcl-2 protein is associated with chemotherapy resistance and decreased survival in chronic lymphocytic leukemia (CLL). We evaluated whether oblimersen would improve response to chemotherapy in patients with relapsed or refractory CLL... CONCLUSION: The addition of oblimersen to fludarabine plus cyclophosphamide significantly increases the CR/nPR rate in patients with relapsed or refractory CLL (particularly fludarabine-sensitive patients), as well as response duration among patients who achieve CR/nPR.
Phase III trial of fludarabine plus cyclophosphamide compared with fludarabine for patients with previously untreated chronic lymphocytic leukemia: US Intergroup Trial E2997. [2007.03.01]
PURPOSE: The combination of fludarabine and cyclophosphamide is an effective regimen for patients with chronic lymphocytic leukemia (CLL). However, it may be accompanied by increased toxicity compared with fludarabine alone. E2997 is a phase III randomized Intergroup trial comparing fludarabine and cyclophosphamide (FC arm) versus fludarabine (F arm) alone in patients receiving their first chemotherapy regimen for CLL... CONCLUSION: Fludarabine and cyclophosphamide produced an increase in OR and CR, and it improved PFS in patients with previously untreated CLL compared with fludarabine alone and was not associated with an increase in infectious toxicity.
Clinical Trials Related to Fludara (Fludarabine)
Fludarabine, Pixantrone and Rituximab vs Fludarabine and Rituximab forRelapsed or Refractory Indolent NHL [Active, not recruiting]
BBR 2778 is a novel aza-anthracenedione that has activity in experimental tumors and reduced
delayed cardiotoxicity in animal models compared to reference standards. This cytotoxic agent
has structural similarities to mitoxantrone as well as general similarities to anthracyclines
(such as the tricyclic central quinoid chromophore7).
This phase III study will compare the efficacy and safety of the combination BBR 2778,
fludarabine, and rituximab with the combination fludarabine and rituximab in patients with
relapsed or refractory indolent non-Hodgkin's lymphoma.
Fludara Phase II Study for Indolent Lymphoma [Completed]
To assess the antitumor effect and safety of Fludara in patients with indolent lymphoma
Phase II Trial of a Chemotherapy Alone Regimen of IV Busulfan (Busulfex), Melphalan and Fludarabine as Myeloablative Regimen Followed by an Allogeneic T-Cell Depleted Hematopoietic Stem Cell Transplant From an HLA-Identical, or HLA-Non Identical Related or Unrelated Donor [Active, not recruiting]
The purpose of this research study is:(1) to determine if high doses of chemotherapy without
total body irradiation can allow selected stem cells to take and grow,(2) to determine if
selected stem cells from the blood or marrow can take and not cause a complication called
graft-versus-host disease (GvHD) and (3) to evaluate the side effects of the combination of
chemotherapy drugs used for these transplants. In the last 10 years we have developed
chemotherapy combinations to be used for this T-cell depleted transplant protocol. By using
three chemotherapy drugs (IV busulfan, melphalan and fludarabine), we hope to have a good
chemotherapy combination to kill cancer cells, and to make the graft take, without the side
effects of total body irradiation. The chemotherapy drugs to be tested in this protocol are
busulfan, melphalan and fludarabine, all of which have been used successfully for stem cell
transplantation, but not given together as in this specific regimen. This is what is being
tested in this study.
Our initial trials in the 1980's with T-cell depleted transplants showed less GvHD, but the
overall results of the transplants were not better. The reason for this was that the stem
cells did not take and engraft in 15% of our adult patients. This failure of the stem cells
to take can leave patients without bone marrow or blood cells necessary for life. Most stem
cell transplants were done using bone marrow (BMA) obtained from the donors. However, if we
give a medication called G-CSF by shots to the donor, we can collect peripheral blood stem
cells (PBSC) and use them for transplant. The advantage of this approach is that we can
collect 2-20 times more stem cells than that obtained from the marrow. It has been proven
that a larger number of stem cells in the graft make it more difficult for the patient to
reject the stem cells. Some donors may be too small to provide peripheral blood stem cells or
they may not want to take G-CSF shots. In these cases the donors will have their marrow
collected in the operating room under general anesthesia.
Stem cell transplants can lead to a condition known as acute graft-versus-host disease or
GvHD. This disease is caused by an assault by certain cells in the marrow or blood (T-cells)
of the donor (graft) against your body (the host). These T-cells see your body as foreign and
attack it. The disease causes a skin rash, liver disease, and diarrhea. Methods were
developed at this institution to prevent GvHD. These methods take out most of the T-cells
(responsible for GvHD) from the marrow or blood stem cells before transplant. This is called
"T-cell depletion" or "stem cell selection". In this hospital, we use two types of methods of
T-cell depletion: one method is used with peripheral blood stem cells and one for bone
marrow. Both these techniques have been successful in preventing both acute and chronic GvHD.
You will receive a T-cell depleted stem cell transplant.
Phase II Study Evaluating Busulfan and Fludarabine as Preparative Therapy in Adults With Hematopoietic Disorders Undergoing MUD SCT [Completed]
The primary objective of this study is to assess the safety and efficacy of performing
unrelated stem cell transplants using intravenous busulfan and fludarabine as preparative
therapy and tacrolimus plus methotrexate as the GVHD prophylaxis regimen. The goal is to
demonstrate safety, aiming for a transplant related mortality rate (TRM) of < or equal to 40%
at 100 days. A TRM of > or equal to 60% will be considered unacceptable. Another goal is to
demonstrate efficacy by showing and overall survival of >40% at 1-year following transplant.
Fludarabine, Mitoxantrone, and Dexamethasone (FND) Plus Rituximab for Lymphoma Patients [Active, not recruiting]
Primary Objectives:
1. To compare molecular response rates with the FND regimen followed by rituximab (chimeric
anti-CD20 antibody) and interferon versus FND plus rituximab concurrently, followed by
interferon, for patients with stage IV indolent lymphoma.
2. To compare the toxicity of these two regimens, including their effects on B- and T-cell
subsets, immunoglobulins, and patterns of infections.
3. To compare failure-free and overall survival rates with these two regimens.
4. To identify and treat with a separate strategy those follicular lymphoma patients
without bcl-2 mbr or mcr gene rearrangement ("germline" patients) because of their
adverse outcome with FND alone in our prior experience.
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Page last updated: 2009-11-19
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