Lymphoma
Conditions
Keywords
Lymphoma
Brief summary
Patients with a low-grade, or indolent (slow-growing) form of non-Hodgkin's lymphoma (NHL) in which the usual survival is between 7-10 years are being asked to take part in this study. Although normally-used combinations of chemotherapy will cause NHL to disappear in 30-40% of patients (called complete response or complete remission), almost all will have their disease return. In this study, researchers tested a combination of anti-cancer agents, fludarabine, rituximab and GM-CSF with mitoxantrone or cyclophosphamide to see if a better and more long-lasting response can be achieved. All of the medications are approved by the Food and Drug Administration (FDA) and are available on the market. The agents we will use are: * Mitoxantrone and fludarabine and cyclophosphamide and fludarabine are combinations of chemotherapy drugs that have been successfully used to treat NHL/CLL (Chronic lymphocytic leukemia) that has returned after treatment and are comparable options for treatment. * Rituximab, a monoclonal antibody that kills cancer cells by binding the CD20 antigen found on the surface of B-cells, commonly used along with chemotherapy drugs to improve response rates in lymphoma treatment. * GM-CSF (granulocyte-macrophage colony stimulating factor, also called sargramostim, GM, or Leukine), a growth factor which stimulates the development of new (stem) cells. GM-CSF encourages stem cells to divide, specialize, and become active. It is not a normal part of treatment for NHL. Using GM-CSF in NHL treatment is the experimental part of this study. The main purpose of this study is to see if giving GM-CSF along with a standard anti-cancer treatment will work better to reduce cancer, and to look at side effects of the treatment.
Detailed description
Patients with a low-grade, or indolent (slow-growing) form of non-Hodgkin's lymphoma (NHL) in which the usual survival is between 7-10 years are being asked to take part in this study. Although normally-used combinations of chemotherapy will cause NHL to disappear in 30-40% of patients (called complete response or complete remission), almost all will have their disease return. When NHL is diagnosed, an abundance of white blood cells called B-lymphocytes (or B-cells) are found in the body. Almost all B-cells have a special protein on the surface called a CD20 antigen. Some anti-cancer drugs, called monoclonal antibodies, target cancer cells by binding, or locking up, specific antigens found on their surfaces, which kills the cancer cells. In this study, researchers will test a combination of anti-cancer agents to see if a better and more long-lasting response can be achieved. All of the medications are approved by the Food and Drug Administration (FDA) and are available on the market. The agents we will use are: -Mitoxantrone and fludarabine, a combination of chemotherapy drugs that has been successfully used to treat NHL that has returned after treatment. OR * Cyclophosphamide and fludarabine, a combination of chemotherapy drugs that has been successfully used to treat NHL that has returned after treatment. * Rituximab, a monoclonal antibody that kills cancer cells by binding the CD20 antigen found on the surface of B-cells, commonly used along with chemotherapy drugs to improve response rates in lymphoma treatment. * GM-CSF (granulocyte-macrophage colony stimulating factor, also called sargramostim, GM, or Leukine), a growth factor which stimulates the development of new (stem) cells. GM-CSF encourages stem cells to divide, specialize, and become active. It is not a normal part of treatment for NHL. Using GM-CSF in NHL treatment is the experimental part of this study. In studies done in the laboratory, GM-CSF caused an increase in the number of antigens, such as CD20, on the surface of B-cells. If more antigens are present, it may be easier to target cells that express CD20 or other antigens. Monoclonal antibodies (such as rituximab) might then be able to more effectively bind the antigens and kill the cancer cells. The main purpose of this study is to see if giving GM-CSF along with a standard anti-cancer treatment will work better to reduce cancer, and to look at side effects of the treatment.
Interventions
DRUGMitoxantrone/Cyclophosphamide, Fludarabine, Rituximab and GM-CSF
Initial patients (n=9) received fludarabine (25 mg/m\^2 intravenously) and mitoxantrone (10 mg/m\^2 intravenously)with sequential administration of GM-CSF(Granulocyte-macrophage colony stimulating factor) (500 µcg subcutaneously) on days 6 and 7 and rituximab (375 mg/m\^2) on day 8. After a change in the protocol, all additional patients (n=6) received fludarabine (25 mg/m\^2 intravenously) and cyclophosphamide (250 mg/m\^2 intravenously)with sequential administration of GM-CSF (500 µcg subcutaneously) on days 6 and 7 and rituximab (375 mg/m\^2) on day 8. All patients received additional doses of GM-CSF (days +8 through +14) were given for patients to reduce variability in neutropenic management.
Sponsors
Bayer
Emory University
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
* To qualify for this study, the patient must have relapsed, refractory or previously untreated low-grade (indolent) non-Hodgkin lymphoma of the following subtypes: Follicular center cell lymphoma grade 1, lymphoplasmacytoid lymphoma, small lymphocytic lymphoma, splenic marginal-zone types lymphoma, monocytoid B-cell lymphoma and extranodal mucosa-associated lymphoid tissue (MALT) lymphomas. Final eligibility will be determined by the health professionals conducting this clinical trial.
Exclusion criteria
* Patients who have received prior treatment with purine analogs will be excluded from this study. Also, patients whose diagnostic/histologic subtype cannot be confirmed by our institution will not be able to participate in this study. Final eligibility will be determined by the health professionals conducting this clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients's Who Had Complete Response and Partial Response to the Treatment of Fludarabine and Cyclophosphamide Followed by GM-CSF and Rituximab. | 6 months | Complete Response (CR): Disappearance of all clinical evidence of active tumor for a minimum of eight weeks and absence of any symptoms related to the tumor. Partial Response (PR):50% decrease in the sum of the product diameters of all lesions that persist for at least four weeks. No lesion can increase in size and no new lesion can appear during this period. Stable disease (SD):A tumor that is neither growing nor shrinking.No new tumors have developed |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fludarabine and Cyclophosphamide With Sequential Administratio Patients will receive fludarabine and cyclophosphamide with sequential administration of GM-CSF on days 6 and 7 and rituximab on day 8. | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | Fludarabine and Cyclophosphamide With Sequential Administratio |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 6 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| Age Continuous | 62 years |
| Diagnosis Type Chronic Lymphocytic Leukemia (CLL) | 8 Participants |
| Diagnosis Type Low Grade Non Hodgkin's Lymphoma(NHL) | 7 Participants |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 15 / 15 |
| serious Total, serious adverse events | 0 / 15 |
Outcome results
Primary
Number of Patients's Who Had Complete Response and Partial Response to the Treatment of Fludarabine and Cyclophosphamide Followed by GM-CSF and Rituximab.
Complete Response (CR): Disappearance of all clinical evidence of active tumor for a minimum of eight weeks and absence of any symptoms related to the tumor. Partial Response (PR):50% decrease in the sum of the product diameters of all lesions that persist for at least four weeks. No lesion can increase in size and no new lesion can appear during this period. Stable disease (SD):A tumor that is neither growing nor shrinking.No new tumors have developed
Time frame: 6 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Chronic Lymphocytic Leukemia | Number of Patients's Who Had Complete Response and Partial Response to the Treatment of Fludarabine and Cyclophosphamide Followed by GM-CSF and Rituximab. | Partial Response | 2 participants |
| Chronic Lymphocytic Leukemia | Number of Patients's Who Had Complete Response and Partial Response to the Treatment of Fludarabine and Cyclophosphamide Followed by GM-CSF and Rituximab. | Complete Response | 4 participants |
| Chronic Lymphocytic Leukemia | Number of Patients's Who Had Complete Response and Partial Response to the Treatment of Fludarabine and Cyclophosphamide Followed by GM-CSF and Rituximab. | Stable Disease | 1 participants |
| Non Hodgkin Lymphoma | Number of Patients's Who Had Complete Response and Partial Response to the Treatment of Fludarabine and Cyclophosphamide Followed by GM-CSF and Rituximab. | Complete Response | 5 participants |
| Non Hodgkin Lymphoma | Number of Patients's Who Had Complete Response and Partial Response to the Treatment of Fludarabine and Cyclophosphamide Followed by GM-CSF and Rituximab. | Partial Response | 2 participants |
| Non Hodgkin Lymphoma | Number of Patients's Who Had Complete Response and Partial Response to the Treatment of Fludarabine and Cyclophosphamide Followed by GM-CSF and Rituximab. | Stable Disease | 0 participants |