Phase II Study of Fludarabine and Mitoxantrone, Followed by GM-CSF(Granulocyte-macrophage Colony-stimulating Factor) and Rituximab

NCT00208975 | Terminated Phase 2 Results DMC

• 1 other identifier: 1048-2001
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Lymphoma

Keywords

Lymphoma

Outcome Measures

Primary Outcomes (1)

• 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

  6 months

Study Arms (1)

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.

Drug: Mitoxantrone/Cyclophosphamide, Fludarabine, Rituximab and GM-CSF

Interventions

Mitoxantrone/Cyclophosphamide, Fludarabine, Rituximab and GM-CSF DRUG

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.

Also known as: Fludara, Sargramostim, Leukine, Rituxan

Fludarabine and Mitoxantrome followed by GM-CSF and Rituximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Emory University: lead
• Bayer: collaborator

Study Sites (1)

Emory University Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Related Publications (1)

• 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.

  PMID: 26297176 DERIVED

MeSH Terms

Conditions

Lymphoma

Interventions

Mitoxantrone; Cyclophosphamide; fludarabine; Rituximab; Granulocyte-Macrophage Colony-Stimulating Factor; fludarabine phosphate; sargramostim

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Quinones; Polycyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors

Limitations and Caveats

The protocol was closed early due to slow and poor accrual.

Results Point of Contact

• Title: Dr. Christopher Flowers
• Organization: Emory University

crflowe@emory.edu

404-778-3942

Study Officials

• Christopher Flowers, MD

  Emory University Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: September 13, 2005
• First Posted: September 21, 2005
• Study Start: July 1, 2002
• Primary Completion: December 1, 2009
• Study Completion: September 1, 2011
• Last Updated: June 28, 2012
• Results First Posted: June 28, 2012

Record last verified: 2012-05

Locations

US (1)