G-CSF Versus G-CSF Plus GM-CSF for Stem Cell Mobilization in NHL Patients

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00499343
• Collaborator: Bayer (Industry)
• Enrollment: 84
• Location: 1
• Arms: 2
• Duration (Months): 57
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

Primary Objectives:

1. To determine the efficacy of in vivo purging achieved by rituximab in the two groups.

2. To determine the number of apheresis procedures, total stem cell yield/kg patient body weight and the toxicity profile in the two groups.

Secondary Objectives:

1. To determine the degree of expression of various adhesion molecules in the 2 groups and correlate with time to engraftment of neutrophils, platelets, and red blood cells, efficacy of stem cell mobilization and purging.

2. To determine the incidence of disease progression/relapse at 12 months in the two groups.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Drug: Etoposide; Drug: G-CSF; Drug: GM-CSF; Drug: Isophosphamide; Drug: Rituximab; Procedure: Apheresis	Phase 2

Detailed Description

Granulocyte-colony stimulating factor (G-CSF) and granulocyte macrophage-colony stimulating factor (GM-CSF) are synthetic (man-made) versions of substances naturally produced in your body. These substances, called colony stimulating factors, help the bone marrow to make new white blood cells. When certain cancer medicines fight your cancer cells, they also affect those white blood cells that fight infection. To help decrease the risk of infections when these cancer medicines are used, colony stimulating factors may be given. Colony stimulating factors are also used to help the bone marrow recover after bone marrow transplantation and stem cell transplantation. They are also used to increase the stem cell count in the blood so that adequate number of stem cells can be collected for purposes of transplantation.

Before the study begins, you will have a complete physical exam and have blood (around 1-2 tablespoons) and urine collected for routine tests. You will have x-rays and CT scans to check on the status of the disease. A sample of bone marrow will be collected for tests. 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a bone marrow sample, an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow is withdrawn through a large needle. Your heart and lung function will be evaluated. You will have an electrocardiogram (ECG - a test that measures the electrical activity of the heart) and either a echocardiogram or a multigated acquisition scan (MUGA) (these are tests that measure heart functions). You will also have lung function tests. Women who are able to have children must have a negative blood or urine pregnancy test.

You will have a plastic tube (central venous catheter - CVL) inserted under your collarbone. The CVL will be left in place for the duration of the treatment. The catheter will be used to deliver most of the drugs and for the collection and transfusion of the stem cells. When possible, all drugs that need to be given by vein will be given using the catheter.

All treatment will be given at M. D. Anderson. First, you will be given chemotherapy to increase the number of stem cells in your blood stream. This chemotherapy will include the drugs ifosfamide, etoposide, and rituximab. You will receive a higher dose of rituximab than is standard of care. The drug ifosfamide will be started on Day 2 and will be given as a continuous injection into a vein over 72 hours. The drug etoposide will also be started on Day 2 and will be given by vein over 2 hours every 12 hours. Rituximab will be given by vein over 4-6 hours on Days 1 and 8. To help decrease the risk of developing side effects caused by the chemotherapy, you will be given fluids by vein and a drug called mesna. Mesna will be given by vein over 24 hours after treatment with ifosfamide is finished. You will have to stay in the hospital for 4-6 days for this part of the treatment.

You will be randomly assigned (as in the toss of a coin) to one of two treatment groups. Participants in one group will receive G-CSF and GM-CSF. Participants in the other group will receive G-CSF alone.

After completion of chemotherapy, you will get GM-CSF and G-CSF or just G-CSF injections (given under the skin) twice a day. These drugs are given to help increase the number of white blood cells and will continue to be given until an adequate number of stem cells have been collected. During this time, you will have blood collected for tests (around 1 tablespoon) at least 3 times a week. If your doctor feels it is necessary, you may have blood collected more often.

Blood stem cells will be collected when your blood counts have returned to normal (about 10-16 days after the chemotherapy). The process of stem cell collection takes about 4 hours. It may take 1-6 sessions to collect the number of stem cells needed for the transplant. The process of stem cell collection is called apheresis. A machine is attached to the catheter under the collar bone and blood is withdrawn. The blood then flows through the machine, which removes stem cells from the blood. The blood is then returned back to you through the catheter. The stem cells are then frozen and stored. These stem cells will be given back to you after the next phase of treatment to help your blood counts recover after high dose chemotherapy. After enough stem cells have been collected, you will be admitted to the hospital for high dose chemotherapy.

You will have check-up visits at various times over the next year as part of your standard evaluation after transplantation to check on the status of the disease.

This is an investigational study. All of the drugs used in this study are FDA approved and are commercially available. Up to 100 patients will take part in this study. All will be enrolled at M. D. Anderson.

Study Design

• Study Type: Interventional
• Actual Enrollment: 84 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Study Comparing Chemotherapy Followed by G-CSF Alone Versus G-CSF Plus GM-CSF for Mobilization of Peripheral Blood Stem Cells in Patients With Non-Hodgkin's Lymphomas
• Study Start Date: Jan 1, 2004
• Actual Primary Completion Date: Oct 1, 2008
• Actual Study Completion Date: Oct 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rituximab + Ifosfamide + Etoposide + 2 Growth Factors Growth Factors = granulocyte-colony stimulating factor (G-CSF) + granulocyte macrophage-colony stimulating factor (GM-CSF)	Drug: Etoposide; 150 mg/m^2 given intravenously over 2 hours every 12 hours x 6 doses.; Other Names: Vepesid ; Drug: G-CSF; Starting dose on day +6 at 6 mcg/kg injection every 12 hours until completion of apheresis.; Other Names: Filgrastim Neupogen ; Drug: GM-CSF; 250 mcg/m^2 injection given every evening till the completion of apheresis.; Other Names: Sargramostim Leukine ; Drug: Isophosphamide; 10 g/m^2 given intravenously continuous infusion over 72 hours.; Other Names: ifosfamide Ifex ; Drug: Rituximab; Days +1 (375 mg/m^2) and +8 (1000 mg/m^2) given intravenously.; Other Names: Rituxan ; Procedure: Apheresis; Peripheral blood stem cell collection.
Experimental: Rituximab + Ifosfamide + Etoposide + 1 Growth Factor Growth Factor = granulocyte-colony stimulating factor (G-CSF)	Drug: Etoposide; 150 mg/m^2 given intravenously over 2 hours every 12 hours x 6 doses.; Other Names: Vepesid ; Drug: G-CSF; Starting dose on day +6 at 6 mcg/kg injection every 12 hours until completion of apheresis.; Other Names: Filgrastim Neupogen ; Drug: Isophosphamide; 10 g/m^2 given intravenously continuous infusion over 72 hours.; Other Names: ifosfamide Ifex ; Drug: Rituximab; Days +1 (375 mg/m^2) and +8 (1000 mg/m^2) given intravenously.; Other Names: Rituxan ; Procedure: Apheresis; Peripheral blood stem cell collection.

Outcome Measures

Primary Outcome Measures

1. CD34+ Cells/kg in Blood Stem Cells [The process of stem cell collections take about 4 hours, 1-6 sessions may be needed.]

   After blood counts return to normal, stem cell collection (takes approximately 4 hours) up to 6 sessions.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients with histologically confirmed CD20 positive B-cell non-Hodgkin's lymphoma who are candidates for autologous stem cell transplantation.

2. Age up to 70 years

3. Platelet count > 100,000 mm3, independent of transfusion support

4. Absolute neutrophil count (ANC) > 1500/mm3

5. Zubrod performance status of 2 or less.

6. Negative pregnancy test in women

7. Less than 10% marrow involvement with lymphoma within 4 weeks of study enrollment as defined by bilateral bone marrow aspirations and biopsies.

8. Should be seronegative for HIV, HTLV, hepatitis B surface antigen, hepatitis C antibody.

Exclusion Criteria:

1. Clinical or radiographic evidence of active CNS disease

2. Severe concomitant medical or psychiatric illness

3. Lactating or breast feeding females

4. Less than 3 weeks from the first day of last chemotherapy

5. Prior myeloablative therapy with autologous bone marrow or stem cell rescue

6. Serum bilirubin > 1.5 X ULN, Serum transaminases > 2XULN.

7. Serum creatinine >1.6 mg/dl

8. History of pelvic radiation

9. Patients should not have received more than 3 prior chemotherapy regimens (excluding radiation)

10. Patients should not have received more than 6 cycles of fludarabine therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	U.T.M.D. Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• Bayer

Investigators

• Principal Investigator: Chitra M. Hosing, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• UT MD Anderson Cancer Center website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT00499343
• Other Study ID Numbers: ID03-0242
• First Posted: Jul 11, 2007
• Last Update Posted: Aug 2, 2013
• Last Verified: Jun 1, 2013

• Keywords provided by M.D. Anderson Cancer Center: Non-Hodgkin's Lymphoma; Lymphoma; Etoposide; G-CSF; GM-CSF; Isophosphamide; Rituximab; Ifosfamide; Sargramostim; Leukine; Filgrastim; Neupogen; Apheresis; Stem Cell Collection
• Additional relevant MeSH terms: Lymphoma; Rituximab; Etoposide; Ifosfamide; Sargramostim

Study Results

Participant Flow

Recruitment Details	Recruitment period: 02/12/2004 through 07/13/2007. All participants recruited at U.T. M.D. Anderson Cancer Center and participating institutions.

Arm/Group Title	Rituximab + Ifosfamide + Etoposide + 2 Growth Factors	Rituximab + Ifosfamide + Etoposide + 1 Growth Factor
Arm/Group Description	Growth Factors = granulocyte-colony stimulating factor (G-CSF) + granulocyte macrophage-colony stimulating factor (GM-CSF)	Growth Factor = granulocyte-colony stimulating factor (G-CSF)
Period Title: Overall Study
STARTED	41	43
COMPLETED	41	43
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Rituximab + Ifosfamide + Etoposide + 2 Growth Factors	Rituximab + Ifosfamide + Etoposide + 1 Growth Factor	Total
Arm/Group Description	Growth Factors = granulocyte-colony stimulating factor (G-CSF) + granulocyte macrophage-colony stimulating factor (GM-CSF)	Growth Factor = granulocyte-colony stimulating factor (G-CSF)	Total of all reporting groups
Overall Participants	41	43	84
Age, Customized (participants) [Number]
Between 20 and 39 years	3 7.3%	4 9.3%	7.0 8.3%
Between 40 and 59 years	26 63.4%	29 67.4%	55.0 65.5%
Between 60 and 79 years	12 29.3%	10 23.3%	22.0 26.2%
Sex: Female, Male (Count of Participants)
Female	17 41.5%	14 32.6%	31.0 36.9%
Male	24 58.5%	29 67.4%	53.0 63.1%
Region of Enrollment (participants) [Number]
United States	41 100%	43 100%	84.0 100%

Outcome Measures

1. Primary Outcome

Title	CD34+ Cells/kg in Blood Stem Cells
Description	After blood counts return to normal, stem cell collection (takes approximately 4 hours) up to 6 sessions.
Time Frame	The process of stem cell collections take about 4 hours, 1-6 sessions may be needed.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rituximab + Ifosfamide + Etoposide + 2 Growth Factors	Rituximab + Ifosfamide + Etoposide + 1 Growth Factor
Arm/Group Description	Growth Factors = granulocyte-colony stimulating factor (G-CSF) + granulocyte macrophage-colony stimulating factor (GM-CSF)	Growth Factor = granulocyte-colony stimulating factor (G-CSF)
Measure Participants	41	43
Median (Full Range) [CD34+ cells/kg]	7.5	10.34

Adverse Events

Time Frame	4 years and 3 months
Arm/Group Title	Rituximab + Ifosfamide + Etoposide + 2 Growth Factors		Rituximab + Ifosfamide + Etoposide + 1 Growth Factor
Arm/Group Description	Growth Factors = granulocyte-colony stimulating factor (G-CSF) + granulocyte macrophage-colony stimulating factor (GM-CSF)		Growth Factor = granulocyte-colony stimulating factor (G-CSF)
All Cause Mortality
	Rituximab + Ifosfamide + Etoposide + 2 Growth Factors		Rituximab + Ifosfamide + Etoposide + 1 Growth Factor
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Rituximab + Ifosfamide + Etoposide + 2 Growth Factors		Rituximab + Ifosfamide + Etoposide + 1 Growth Factor
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/41 (0%)		0/43 (0%)
Other (Not Including Serious) Adverse Events
	Rituximab + Ifosfamide + Etoposide + 2 Growth Factors		Rituximab + Ifosfamide + Etoposide + 1 Growth Factor
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/41 (24.4%)		10/43 (23.3%)
Blood and lymphatic system disorders
CYTOKINE RELEASE SYNDROME	2/41 (4.9%)		0/43 (0%)
FEBRILE NEUTROPENIA	7/41 (17.1%)		6/43 (14%)
ANEMIA	1/41 (2.4%)		2/43 (4.7%)
Gastrointestinal disorders
NAUSEA/VOMITING	0/41 (0%)		2/43 (4.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.