LymphomaPhase 2NCT00208975
Phase II Study of Fludarabine and Mitoxantrone, Followed by GM-CSF(Granulocyte-macrophage Colony-stimulating Factor) and Rituximab
A Phase 2 study testing Mitoxantrone/Cyclophosphamide, Fludarabine, Rituximab and GM-CSF in people with Lymphoma, run by Emory University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma
- What is being tested?
- Mitoxantrone/Cyclophosphamide, Fludarabine, Rituximab and GM-CSF
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2002to Sep 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Emory University Winship Cancer Institute
Atlanta, Georgia, 30322
About this study
Official title: Phase II Study of Fludarabine and Mitoxantrone, Followed by GM-CSF(Granulocyte-macrophage Colony-stimulating Factor) and Rituximab in Patients With Low Grade Non-Hodgkins Lymphoma: An Analysis of Efficacy and Tolerability
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:
Read more
- 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.
Read the 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.
- Conditions
- Lymphoma
- Being tested
- Mitoxantrone/Cyclophosphamide, Fludarabine, Rituximab and GM-CSF
- Keywords
- Lymphoma
- Medical subject headings
- Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mitoxantrone/Cyclophosphamide, Fludarabine, Rituximab and GM-CSFDrug
Also called Fludara, Sargramostim, Leukine, Rituxan
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.
| Study group | Role | What they receive |
|---|---|---|
| Fludarabine and Mitoxantrome followed by GM-CSF and Rituximab | Active comparator | Initial patients (n=9) received fludarabine (25 mg/m2 IV) and mitoxantrone (10 mg/m2 IV)with sequential administration of GM-CSF (500 mcg subcutaneously) on days 6 and 7 and rituximab (375 mg/m2) on day 8.
After a change in the protocol, all additional patients (n=6) received fludarabine (25 mg/m2 IV) and cyclophosphamide (250 mg/m2 IV)with sequential administration of GM-CSF (500 mcg subcutaneously) on days 6 and 7 and rituximab (375 mg/m2) on day 8. All patients received dditional doses of GM-CSF (days +8 through +14) were given for patients to reduce variability in neutropenic management. Receives: Drug: Mitoxantrone/Cyclophosphamide, Fludarabine, Rituximab and GM-CSF |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2005 (estimated)
- Study startJul 2002
- Primary completionDec 2009
- Study completionSep 2011
Why it stopped: slow accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer
- Responsible party
- Principal investigator, Christopher R. Flowers, Emory University
- Investigators
- Christopher Flowers, MD, Principal investigator, Emory University Winship Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00208975
- Sponsor's protocol ID
- 1048-2001
- Status last verified
- May 2012
- First submitted
- 13 Sep 2005
- Last updated
- 28 Jun 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Cohen JB, Bucur S, Winton EF, Sinha R, Heffner LT, King N, Lonial S, Langston AA, Waller EK, Hutchison-Rzepka A, Colbert A, Lechowicz MJ, Flowers CR. Combination of GM-CSF With Fludarabine-Containing Regimens in Chronic Lymphocytic Leukemia and Indolent Non-Hodgkin Lymphoma. Clin Lymphoma Myeloma Leuk. 2015 Sep;15(9):514-8. doi: 10.1016/j.clml.2015.06.009. Epub 2015 Jul 3.
PubMed 26297176
Study at a glance
From the registry record, last updated by the sponsor on 28 Jun 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Fludarabine and Mitoxantrone, Followed by GM-CSF(Granulocyte-macrophage Colony-stimulating Factor) and Rituximab in Patients With Low Grade Non-Hodgkins Lymphoma: An Analysis of Efficacy and Tolerability
- ClinicalTrials.gov ID
- NCT00208975
- Acronym / sponsor ID
- 1048-2001
- Conditions
- Lymphoma
- Keywords
- Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: slow accrual
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- Bayer
- Study start
- Jul 2002
- Primary completion
- Dec 2009 (actual)
- Study completion
- Sep 2011 (actual)
- First posted
- 21 Sep 2005 (estimated)
- Results
- Posted 28 Jun 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Fludarabine and Mitoxantrome followed by GM-CSF and Rituximab | Active comparator | Drug: Mitoxantrone/Cyclophosphamide, Fludarabine, Rituximab and GM-CSFInitial patients (n=9) received fludarabine (25 mg/m2 IV) and mitoxantrone (10 mg/m2 IV)with sequential administration of GM-CSF (500 mcg subcutaneously) on days 6 and 7 and rituximab (375 mg/m2) on day 8. After a change in the protocol, all additional patients (n=6) received fludarabine (25 mg/m2 IV) and cyclophosphamide (250 mg/m2 IV)with sequential administration of GM-CSF (500 mcg subcutaneously) on days 6 and 7 and rituximab (375 mg/m2) on day 8. All patients received dditional doses of GM-CSF (days +8 through +14) were given for patients to reduce variability in neutropenic management. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (1 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mitoxantrone/Cyclophosphamide, Fludarabine, Rituximab and GM-CSFAlso: Fludara, Sargramostim, Leukine, RituxanInitial 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. | Drug | Fludarabine and Mitoxantrome followed by GM-CSF and Rituximab |
Primary outcome
Number of Patients's Who Had Complete Response and Partial Response to the Treatment of Fludarabine and Cyclophosphamide Followed by GM-CSF and Rituximab.
Time frame: 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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26297176Cohen JB, Bucur S, Winton EF, Sinha R, Heffner LT, King N, Lonial S, Langston AA, Waller EK, Hutchison-Rzepka A, Colbert A, Lechowicz MJ, Flowers CR. Combination of GM-CSF With Fludarabine-Containing Regimens in Chronic Lymphocytic Leukemia and Indolent Non-Hodgkin Lymphoma. Clin Lymphoma Myeloma Leuk. 2015 Sep;15(9):514-8. doi: 10.1016/j.clml.2015.06.009. Epub 2015 Jul 3.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christopher Flowers, MD principal investigator
Emory University Winship Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Mitoxantrone/Cyclophosphamide, Fludarabine, Rituximab and GM-CSF in people with Lymphoma, run by Emory University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Jun 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Jun 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients's Who Had Complete Response and Partial Response to the Treatment of Fludarabine and Cyclophosphamide Followed by GM-CSF and Rituximab. (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00208975, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jun 2012.