Cyclophosphamide for Hematopoietic Stem Cell Mobilization in Patients With a Hematologic Malignancy

• Sponsor: Dartmouth-Hitchcock Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT02139280
• Collaborator: (none)
• Enrollment: 58
• Location: 1
• Arms: 2
• Duration (Months): 81
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

No prospective randomized trials have evaluated the most efficacious dose of cyclophosphamide to mobilize autologous stem cells. We previously demonstrated that the time to collection of autologous hematopoietic stem cells is 10-12 days following the one dose of cyclophosphamide and daily G-CSF (granulocyte-colony stimulating factor).9 This prospective randomized trial is designed to determine if a lower dose of cyclophosphamide (1.5 gm/m2) will be as efficacious as the intermediate dose (3 gm/m2), based on cell number collected, number of apheresis required and resource utilization.

Condition or Disease	Intervention/Treatment	Phase
Hematologic Malignancies	Drug: Cyclophosphamide	Phase 2

Detailed Description

This prospective randomized trial is designed to determine if a lower dose of cyclophosphamide (1.5 gm/m2) will be as efficacious as the intermediate dose (3 gm/m2), based on cell number collected, number of apheresis required and resource utilization.

The time to collection of autologous hematopoietic stem cells was ten to twelve days following cyclophosphamide and daily filgrastim. Peripheral blood CD34+ cell numbers were examined beginning ten days after cyclophosphamide administration. Leukapheresis began once the blood CD34+ number reached 10 cells/mcl. Patients received consecutive days of leukapheresis, with the goal of collecting > 5 x 106 CD34+cells/kg. The collection process, concentration and storage of PBSC were similar for all patients. Briefly, a 4-blood volume leukapheresis PBSC collection was performed daily using a COBE Spectra cell separator (COBE BCT, Lakewood, CO). Collected cells were concentrated and cryopreserved. Cells were frozen in Cryocyte freezing bags (Nexell Therapeutics Inc.) in a controlled rate freezer (Custom BioGenic Systems, Shelby Township, MI). At the conclusion of this freezing, the cells were transferred to the vapor phase of a monitored liquid nitrogen freezer (CryoPlus III, Forma Scientific, Marietta, OH) at a temperature of -120 0C or below.

Study Design

• Study Type: Interventional
• Actual Enrollment: 58 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Prospective Randomized Trial Examining Low- or Intermediate-Dose Cyclophosphamide for Hematopoietic Stem Cell Mobilization in Patients With a Hematologic Malignancy
• Study Start Date: Dec 1, 2013
• Actual Primary Completion Date: Jul 1, 2019
• Actual Study Completion Date: Sep 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm 2: Cyclophosphamide 3 gms/m(2) Patients will receive intravenous mesna 15 minutes prior to cyclophosphamide and again at 4 and 8 hours afterwards. Each infusion will be given over 15 minutes. Oral mesna can be substituted for the two post-cyclophosphamide doses. Oral mesna will be administered at 2 and 6 hours after the start of cyclophosphamide. Cyclophosphamide will be administered intravenously over one hour at the dose of 3 gms/m(2).	Drug: Cyclophosphamide; Mechanism of action: Cyclophosphamide is a pro drug that requires activation. Following hepatic and cellular activation, phosphoramide mustard and acrolein are formed. Phosphoramide mustard is the alkylating agent that demonstrates cytotoxic effects. Acrolein binds to proteins but does not contribute to the anti-tumor effects.; Other Names: Endoxan Cytoxan Neosar Procytox Revimmune Cytophosphane
Experimental: Arm 1: 1.5 gms/m(2) Cyclophosphamide Patients will receive intravenous mesna 15 minutes prior to cyclophosphamide and again at 4 and 8 hours afterwards. Each infusion will be given over 15 minutes. Oral mesna can be substituted for the two post-cyclophosphamide doses. Oral mesna will be administered at 2 and 6 hours after the start of cyclophosphamide. Cyclophosphamide will be administered intravenously over one hour at the dose of 1.5 gms/m(2).	Drug: Cyclophosphamide; Mechanism of action: Cyclophosphamide is a pro drug that requires activation. Following hepatic and cellular activation, phosphoramide mustard and acrolein are formed. Phosphoramide mustard is the alkylating agent that demonstrates cytotoxic effects. Acrolein binds to proteins but does not contribute to the anti-tumor effects.; Other Names: Endoxan Cytoxan Neosar Procytox Revimmune Cytophosphane

Outcome Measures

Primary Outcome Measures

1. Number of Nucleated Cells Collected Within the Apheresis Products [6 weeks]

   the investigator will identify the number of cells collected within the apheresis products

2. Number of CD34+ Cells Collected Within the Apheresis Products [6 weeks]

   the investigator will identify the number of CD34+ cells collected within the apheresis products

Secondary Outcome Measures

1. Resource Utilization - Transfusions of Red Blood Cells [participants will be followed approximately 6 weeks following initiation of treatment]

   Resources used during the mobilization and apheresis processes will be captured.

2. Resource Utilization- Transfusion of Platelets [participants will be followed approximately 6 weeks following initiation of treatment]

   Resources used during the mobilization and apheresis processes will be captured.

3. Resource Utilization- Hospitalizations [participants will be followed approximately 6 weeks following initiation of treatment]

   Resources used during the mobilization and apheresis processes will be captured.

4. Resource Utilization- Incidence of Febrile Neutropenia [participants will be followed approximately 6 weeks following initiation of treatment]

   Resources used during the mobilization and apheresis processes will be captured.

5. Toxicities During the Mobilization and Apheresis Processes [participants will be followed approximately 6 weeks following initiation of treatment]

   Toxicities during the mobilization and apheresis processes Grade 3 and higher

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• All patients must have a pathologic diagnosis of one of the following malignancies:

Non-Hodgkin's Lymphoma, including B- and T-cell lymphoma Multiple Myeloma or another plasma cell dyscrasia (Waldenstrom, Amyloidosis)

• The patient must be approved for transplant by the treating Transplant physician.

• This must be the patient's FIRST mobilization attempt.

• Patients are eligible if an autologous transplant is planned within approximately 12 months from the time of collection of cells.

• Prior Treatment: No previous cytotoxic chemotherapy within 4 weeks prior to initiation of therapy. (This does not include immunomodulatory drugs (IMiDs), proteasome inhibitors, monoclonal antibodies or steroids.)

• No radiation within 4 weeks of mobilization attempt.

• Age >18, and < 75 years

• No significant co-morbid medical or psychiatric illness that would significantly compromise the patient's clinical care and chances of survival.

• Informed consent must be signed prior to the treatment. Patients must willingly consent after being informed of the procedure to be followed, the nature of the therapy, alternatives, potential benefits, side effects, risks and discomforts. (Human protection committee approval of this protocol and a consent form is required.)

Exclusion Criteria:

• Medical, social, or psychological factors that would prevent the patient from receiving or cooperating with the full course of therapy.

• Documented hypersensitivity to any of the drugs used in the protocol.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756

Sponsors and Collaborators

• Dartmouth-Hitchcock Medical Center

Investigators

• Principal Investigator: Kenneth Meehan, MD, Dartmouth-Hitchcock Medical Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 23, 2020

More Information

Publications

None provided.

• Responsible Party: Kenneth Meehan, Director, Bone Marrow Transplant Program, Dartmouth-Hitchcock Medical Center
• ClinicalTrials.gov Identifier: NCT02139280
• Other Study ID Numbers: D13179
• First Posted: May 15, 2014
• Last Update Posted: Feb 16, 2021
• Last Verified: Jan 1, 2021

• Keywords provided by Kenneth Meehan, Director, Bone Marrow Transplant Program, Dartmouth-Hitchcock Medical Center: Cyclophosphamide; Hematopoietic; Stem Cell; Mobilization; Hematologic Malignancy
• Additional relevant MeSH terms: Neoplasms; Hematologic Neoplasms; Cyclophosphamide

Study Results

Participant Flow

Pre-assignment Detail	58 Individuals provided informed consent. Of those. four (4) participants were screen failures.

Arm/Group Title	Arm 1: 1.5 Gms/m(2) Cyclophosphamide	Arm 2: Cyclophosphamide 3 Gms/m(2)
Arm/Group Description	Patients will receive intravenous mesna 15 minutes prior to cyclophosphamide and again at 4 and 8 hours afterwards. Each infusion will be given over 15 minutes. Oral mesna can be substituted for the two post-cyclophosphamide doses. Oral mesna will be administered at 2 and 6 hours after the start of cyclophosphamide. Cyclophosphamide will be administered intravenously over one hour at the dose of 1.5 gms/m(2). Cyclophosphamide: Mechanism of action: Cyclophosphamide is a pro drug that requires activation. Following hepatic and cellular activation, phosphoramide mustard and acrolein are formed. Phosphoramide mustard is the alkylating agent that demonstrates cytotoxic effects. Acrolein binds to proteins but does not contribute to the anti-tumor effects.	Patients will receive intravenous mesna 15 minutes prior to cyclophosphamide and again at 4 and 8 hours afterwards. Each infusion will be given over 15 minutes. Oral mesna can be substituted for the two post-cyclophosphamide doses. Oral mesna will be administered at 2 and 6 hours after the start of cyclophosphamide. Cyclophosphamide will be administered intravenously over one hour at the dose of 3 gms/m(2). Cyclophosphamide: Mechanism of action: Cyclophosphamide is a pro drug that requires activation. Following hepatic and cellular activation, phosphoramide mustard and acrolein are formed. Phosphoramide mustard is the alkylating agent that demonstrates cytotoxic effects. Acrolein binds to proteins but does not contribute to the anti-tumor effects.
Period Title: Overall Study
STARTED	34	20
COMPLETED	32	20
NOT COMPLETED	2	0

Baseline Characteristics

Arm/Group Title	Arm 1: 1.5 Gms/m(2) Cyclophosphamide	Arm 2: Cyclophosphamide 3 Gms/m(2)	Total
Arm/Group Description	Patients will receive intravenous mesna 15 minutes prior to cyclophosphamide and again at 4 and 8 hours afterwards. Each infusion will be given over 15 minutes. Oral mesna can be substituted for the two post-cyclophosphamide doses. Oral mesna will be administered at 2 and 6 hours after the start of cyclophosphamide. Cyclophosphamide will be administered intravenously over one hour at the dose of 1.5 gms/m(2). Cyclophosphamide: Mechanism of action: Cyclophosphamide is a pro drug that requires activation. Following hepatic and cellular activation, phosphoramide mustard and acrolein are formed. Phosphoramide mustard is the alkylating agent that demonstrates cytotoxic effects. Acrolein binds to proteins but does not contribute to the anti-tumor effects.	Patients will receive intravenous mesna 15 minutes prior to cyclophosphamide and again at 4 and 8 hours afterwards. Each infusion will be given over 15 minutes. Oral mesna can be substituted for the two post-cyclophosphamide doses. Oral mesna will be administered at 2 and 6 hours after the start of cyclophosphamide. Cyclophosphamide will be administered intravenously over one hour at the dose of 3 gms/m(2). Cyclophosphamide: Mechanism of action: Cyclophosphamide is a pro drug that requires activation. Following hepatic and cellular activation, phosphoramide mustard and acrolein are formed. Phosphoramide mustard is the alkylating agent that demonstrates cytotoxic effects. Acrolein binds to proteins but does not contribute to the anti-tumor effects.	Total of all reporting groups
Overall Participants	32	20	52
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	62.5	61.3	61.9
Sex: Female, Male (Count of Participants)
Female	11 34.4%	10 50%	21 40.4%
Male	21 65.6%	10 50%	31 59.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	32 100%	20 100%	52 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	32 100%	20 100%	52 100%

Outcome Measures

1. Primary Outcome

Title	Number of Nucleated Cells Collected Within the Apheresis Products
Description	the investigator will identify the number of cells collected within the apheresis products
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1: 1.5 Gms/m(2) Cyclophosphamide	Arm 2: Cyclophosphamide 3 Gms/m(2)
Arm/Group Description	Patients will receive intravenous mesna 15 minutes prior to cyclophosphamide and again at 4 and 8 hours afterwards. Each infusion will be given over 15 minutes. Oral mesna can be substituted for the two post-cyclophosphamide doses. Oral mesna will be administered at 2 and 6 hours after the start of cyclophosphamide. Cyclophosphamide will be administered intravenously over one hour at the dose of 1.5 gms/m(2). Cyclophosphamide: Mechanism of action: Cyclophosphamide is a pro drug that requires activation. Following hepatic and cellular activation, phosphoramide mustard and acrolein are formed. Phosphoramide mustard is the alkylating agent that demonstrates cytotoxic effects. Acrolein binds to proteins but does not contribute to the anti-tumor effects.	Patients will receive intravenous mesna 15 minutes prior to cyclophosphamide and again at 4 and 8 hours afterwards. Each infusion will be given over 15 minutes. Oral mesna can be substituted for the two post-cyclophosphamide doses. Oral mesna will be administered at 2 and 6 hours after the start of cyclophosphamide. Cyclophosphamide will be administered intravenously over one hour at the dose of 3 gms/m(2). Cyclophosphamide: Mechanism of action: Cyclophosphamide is a pro drug that requires activation. Following hepatic and cellular activation, phosphoramide mustard and acrolein are formed. Phosphoramide mustard is the alkylating agent that demonstrates cytotoxic effects. Acrolein binds to proteins but does not contribute to the anti-tumor effects.
Measure Participants	32	20
Median (Full Range) [cells x10e10]	5.7	3.8

2. Primary Outcome

Title	Number of CD34+ Cells Collected Within the Apheresis Products
Description	the investigator will identify the number of CD34+ cells collected within the apheresis products
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1: 1.5 Gms/m(2) Cyclophosphamide	Arm 2: Cyclophosphamide 3 Gms/m(2)
Arm/Group Description	Patients will receive intravenous mesna 15 minutes prior to cyclophosphamide and again at 4 and 8 hours afterwards. Each infusion will be given over 15 minutes. Oral mesna can be substituted for the two post-cyclophosphamide doses. Oral mesna will be administered at 2 and 6 hours after the start of cyclophosphamide. Cyclophosphamide will be administered intravenously over one hour at the dose of 1.5 gms/m(2). Cyclophosphamide: Mechanism of action: Cyclophosphamide is a pro drug that requires activation. Following hepatic and cellular activation, phosphoramide mustard and acrolein are formed. Phosphoramide mustard is the alkylating agent that demonstrates cytotoxic effects. Acrolein binds to proteins but does not contribute to the anti-tumor effects.	Patients will receive intravenous mesna 15 minutes prior to cyclophosphamide and again at 4 and 8 hours afterwards. Each infusion will be given over 15 minutes. Oral mesna can be substituted for the two post-cyclophosphamide doses. Oral mesna will be administered at 2 and 6 hours after the start of cyclophosphamide. Cyclophosphamide will be administered intravenously over one hour at the dose of 3 gms/m(2). Cyclophosphamide: Mechanism of action: Cyclophosphamide is a pro drug that requires activation. Following hepatic and cellular activation, phosphoramide mustard and acrolein are formed. Phosphoramide mustard is the alkylating agent that demonstrates cytotoxic effects. Acrolein binds to proteins but does not contribute to the anti-tumor effects.
Measure Participants	32	20
Median (Full Range) [cells x10e8]	7	10.5

3. Secondary Outcome

Title	Resource Utilization - Transfusions of Red Blood Cells
Description	Resources used during the mobilization and apheresis processes will be captured.
Time Frame	participants will be followed approximately 6 weeks following initiation of treatment

Outcome Measure Data

Analysis Population Description

Data was not collected due to the large geographic areas of the patient residence. It was too difficult to collect the date from multiple physicians from multiple states.

Arm/Group Title	Arm 1: 1.5 Gms/m(2) Cyclophosphamide	Arm 2: Cyclophosphamide 3 Gms/m(2)
Arm/Group Description	Patients will receive intravenous mesna 15 minutes prior to cyclophosphamide and again at 4 and 8 hours afterwards. Each infusion will be given over 15 minutes. Oral mesna can be substituted for the two post-cyclophosphamide doses. Oral mesna will be administered at 2 and 6 hours after the start of cyclophosphamide. Cyclophosphamide will be administered intravenously over one hour at the dose of 1.5 gms/m(2). Cyclophosphamide: Mechanism of action: Cyclophosphamide is a pro drug that requires activation. Following hepatic and cellular activation, phosphoramide mustard and acrolein are formed. Phosphoramide mustard is the alkylating agent that demonstrates cytotoxic effects. Acrolein binds to proteins but does not contribute to the anti-tumor effects.	Patients will receive intravenous mesna 15 minutes prior to cyclophosphamide and again at 4 and 8 hours afterwards. Each infusion will be given over 15 minutes. Oral mesna can be substituted for the two post-cyclophosphamide doses. Oral mesna will be administered at 2 and 6 hours after the start of cyclophosphamide. Cyclophosphamide will be administered intravenously over one hour at the dose of 3 gms/m(2). Cyclophosphamide: Mechanism of action: Cyclophosphamide is a pro drug that requires activation. Following hepatic and cellular activation, phosphoramide mustard and acrolein are formed. Phosphoramide mustard is the alkylating agent that demonstrates cytotoxic effects. Acrolein binds to proteins but does not contribute to the anti-tumor effects.
Measure Participants	0	0

4. Secondary Outcome

Title	Resource Utilization- Transfusion of Platelets
Description	Resources used during the mobilization and apheresis processes will be captured.
Time Frame	participants will be followed approximately 6 weeks following initiation of treatment

Outcome Measure Data

Analysis Population Description

Data was not collected due to the large geographic areas of the patient residence. It was too difficult to collect the date from multiple physicians from multiple states.

Arm/Group Title	Arm 1: 1.5 Gms/m(2) Cyclophosphamide	Arm 2: Cyclophosphamide 3 Gms/m(2)
Arm/Group Description	Patients will receive intravenous mesna 15 minutes prior to cyclophosphamide and again at 4 and 8 hours afterwards. Each infusion will be given over 15 minutes. Oral mesna can be substituted for the two post-cyclophosphamide doses. Oral mesna will be administered at 2 and 6 hours after the start of cyclophosphamide. Cyclophosphamide will be administered intravenously over one hour at the dose of 1.5 gms/m(2). Cyclophosphamide: Mechanism of action: Cyclophosphamide is a pro drug that requires activation. Following hepatic and cellular activation, phosphoramide mustard and acrolein are formed. Phosphoramide mustard is the alkylating agent that demonstrates cytotoxic effects. Acrolein binds to proteins but does not contribute to the anti-tumor effects.	Patients will receive intravenous mesna 15 minutes prior to cyclophosphamide and again at 4 and 8 hours afterwards. Each infusion will be given over 15 minutes. Oral mesna can be substituted for the two post-cyclophosphamide doses. Oral mesna will be administered at 2 and 6 hours after the start of cyclophosphamide. Cyclophosphamide will be administered intravenously over one hour at the dose of 3 gms/m(2). Cyclophosphamide: Mechanism of action: Cyclophosphamide is a pro drug that requires activation. Following hepatic and cellular activation, phosphoramide mustard and acrolein are formed. Phosphoramide mustard is the alkylating agent that demonstrates cytotoxic effects. Acrolein binds to proteins but does not contribute to the anti-tumor effects.
Measure Participants	0	0

5. Secondary Outcome

Title	Resource Utilization- Hospitalizations
Description	Resources used during the mobilization and apheresis processes will be captured.
Time Frame	participants will be followed approximately 6 weeks following initiation of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1: 1.5 Gms/m(2) Cyclophosphamide	Arm 2: Cyclophosphamide 3 Gms/m(2)
Arm/Group Description	Patients will receive intravenous mesna 15 minutes prior to cyclophosphamide and again at 4 and 8 hours afterwards. Each infusion will be given over 15 minutes. Oral mesna can be substituted for the two post-cyclophosphamide doses. Oral mesna will be administered at 2 and 6 hours after the start of cyclophosphamide. Cyclophosphamide will be administered intravenously over one hour at the dose of 1.5 gms/m(2). Cyclophosphamide: Mechanism of action: Cyclophosphamide is a pro drug that requires activation. Following hepatic and cellular activation, phosphoramide mustard and acrolein are formed. Phosphoramide mustard is the alkylating agent that demonstrates cytotoxic effects. Acrolein binds to proteins but does not contribute to the anti-tumor effects.	Patients will receive intravenous mesna 15 minutes prior to cyclophosphamide and again at 4 and 8 hours afterwards. Each infusion will be given over 15 minutes. Oral mesna can be substituted for the two post-cyclophosphamide doses. Oral mesna will be administered at 2 and 6 hours after the start of cyclophosphamide. Cyclophosphamide will be administered intravenously over one hour at the dose of 3 gms/m(2). Cyclophosphamide: Mechanism of action: Cyclophosphamide is a pro drug that requires activation. Following hepatic and cellular activation, phosphoramide mustard and acrolein are formed. Phosphoramide mustard is the alkylating agent that demonstrates cytotoxic effects. Acrolein binds to proteins but does not contribute to the anti-tumor effects.
Measure Participants	32	20
Count of Participants [Participants]	1 3.1%	1 5%

6. Secondary Outcome

Title	Resource Utilization- Incidence of Febrile Neutropenia
Description	Resources used during the mobilization and apheresis processes will be captured.
Time Frame	participants will be followed approximately 6 weeks following initiation of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1: 1.5 Gms/m(2) Cyclophosphamide	Arm 2: Cyclophosphamide 3 Gms/m(2)
Arm/Group Description	Patients will receive intravenous mesna 15 minutes prior to cyclophosphamide and again at 4 and 8 hours afterwards. Each infusion will be given over 15 minutes. Oral mesna can be substituted for the two post-cyclophosphamide doses. Oral mesna will be administered at 2 and 6 hours after the start of cyclophosphamide. Cyclophosphamide will be administered intravenously over one hour at the dose of 1.5 gms/m(2). Cyclophosphamide: Mechanism of action: Cyclophosphamide is a pro drug that requires activation. Following hepatic and cellular activation, phosphoramide mustard and acrolein are formed. Phosphoramide mustard is the alkylating agent that demonstrates cytotoxic effects. Acrolein binds to proteins but does not contribute to the anti-tumor effects.	Patients will receive intravenous mesna 15 minutes prior to cyclophosphamide and again at 4 and 8 hours afterwards. Each infusion will be given over 15 minutes. Oral mesna can be substituted for the two post-cyclophosphamide doses. Oral mesna will be administered at 2 and 6 hours after the start of cyclophosphamide. Cyclophosphamide will be administered intravenously over one hour at the dose of 3 gms/m(2). Cyclophosphamide: Mechanism of action: Cyclophosphamide is a pro drug that requires activation. Following hepatic and cellular activation, phosphoramide mustard and acrolein are formed. Phosphoramide mustard is the alkylating agent that demonstrates cytotoxic effects. Acrolein binds to proteins but does not contribute to the anti-tumor effects.
Measure Participants	32	20
Count of Participants [Participants]	2 6.3%	2 10%

7. Secondary Outcome

Title	Toxicities During the Mobilization and Apheresis Processes
Description	Toxicities during the mobilization and apheresis processes Grade 3 and higher
Time Frame	participants will be followed approximately 6 weeks following initiation of treatment

Outcome Measure Data

Analysis Population Description

Number of participants who experienced a grade 3 or higher adverse event

Arm/Group Title	Arm 1: 1.5 Gms/m(2) Cyclophosphamide	Arm 2: Cyclophosphamide 3 Gms/m(2)
Arm/Group Description	Patients will receive intravenous mesna 15 minutes prior to cyclophosphamide and again at 4 and 8 hours afterwards. Each infusion will be given over 15 minutes. Oral mesna can be substituted for the two post-cyclophosphamide doses. Oral mesna will be administered at 2 and 6 hours after the start of cyclophosphamide. Cyclophosphamide will be administered intravenously over one hour at the dose of 1.5 gms/m(2). Cyclophosphamide: Mechanism of action: Cyclophosphamide is a pro drug that requires activation. Following hepatic and cellular activation, phosphoramide mustard and acrolein are formed. Phosphoramide mustard is the alkylating agent that demonstrates cytotoxic effects. Acrolein binds to proteins but does not contribute to the anti-tumor effects.	Patients will receive intravenous mesna 15 minutes prior to cyclophosphamide and again at 4 and 8 hours afterwards. Each infusion will be given over 15 minutes. Oral mesna can be substituted for the two post-cyclophosphamide doses. Oral mesna will be administered at 2 and 6 hours after the start of cyclophosphamide. Cyclophosphamide will be administered intravenously over one hour at the dose of 3 gms/m(2). Cyclophosphamide: Mechanism of action: Cyclophosphamide is a pro drug that requires activation. Following hepatic and cellular activation, phosphoramide mustard and acrolein are formed. Phosphoramide mustard is the alkylating agent that demonstrates cytotoxic effects. Acrolein binds to proteins but does not contribute to the anti-tumor effects.
Measure Participants	32	20
Count of Participants [Participants]	4 12.5%	7 35%

Adverse Events

Time Frame	Monitoring of toxicities will terminate on the last day of collection, since treatment-related toxicities occur during this time period. Patients who complete mobilization will be considered "off treatment" on the date of the last mobilization. There will be no specified follow up beyond the off treatment period other than following for engraftment. Average period of data collection was 10 days
Adverse Event Reporting Description	Evaluation of toxicities (other than Hematologic) will be graded using National Cancer Institute Common Toxicity Criteria, specifically CTC AE 4.0.
Arm/Group Title	Arm 1: 1.5 Gms/m(2) Cyclophosphamide		Arm 2: Cyclophosphamide 3 Gms/m(2)
Arm/Group Description	Patients will receive intravenous mesna 15 minutes prior to cyclophosphamide and again at 4 and 8 hours afterwards. Each infusion will be given over 15 minutes. Oral mesna can be substituted for the two post-cyclophosphamide doses. Oral mesna will be administered at 2 and 6 hours after the start of cyclophosphamide. Cyclophosphamide will be administered intravenously over one hour at the dose of 1.5 gms/m(2). Cyclophosphamide: Mechanism of action: Cyclophosphamide is a pro drug that requires activation. Following hepatic and cellular activation, phosphoramide mustard and acrolein are formed. Phosphoramide mustard is the alkylating agent that demonstrates cytotoxic effects. Acrolein binds to proteins but does not contribute to the anti-tumor effects.		Patients will receive intravenous mesna 15 minutes prior to cyclophosphamide and again at 4 and 8 hours afterwards. Each infusion will be given over 15 minutes. Oral mesna can be substituted for the two post-cyclophosphamide doses. Oral mesna will be administered at 2 and 6 hours after the start of cyclophosphamide. Cyclophosphamide will be administered intravenously over one hour at the dose of 3 gms/m(2). Cyclophosphamide: Mechanism of action: Cyclophosphamide is a pro drug that requires activation. Following hepatic and cellular activation, phosphoramide mustard and acrolein are formed. Phosphoramide mustard is the alkylating agent that demonstrates cytotoxic effects. Acrolein binds to proteins but does not contribute to the anti-tumor effects.
All Cause Mortality
	Arm 1: 1.5 Gms/m(2) Cyclophosphamide		Arm 2: Cyclophosphamide 3 Gms/m(2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/33 (0%)		0/20 (0%)
Serious Adverse Events
	Arm 1: 1.5 Gms/m(2) Cyclophosphamide		Arm 2: Cyclophosphamide 3 Gms/m(2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/33 (3%)		2/20 (10%)
Infections and infestations
Infection	1/33 (3%)	1	2/20 (10%)	2
Other (Not Including Serious) Adverse Events
	Arm 1: 1.5 Gms/m(2) Cyclophosphamide		Arm 2: Cyclophosphamide 3 Gms/m(2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/33 (48.5%)		8/20 (40%)
Blood and lymphatic system disorders
Platelets	0/33 (0%)	0	5/20 (25%)	5
Edema: limb	1/33 (3%)	1	1/20 (5%)	1
Cardiac disorders
Sinus tachycardia	1/33 (3%)	1	0/20 (0%)	0
Hypotension	1/33 (3%)	1	0/20 (0%)	0
Gastrointestinal disorders
Nausea	0/33 (0%)	0	1/20 (5%)	1
Diarrhea	1/33 (3%)	1	0/20 (0%)	0
Pain: Abdomen NOS	1/33 (3%)	1	0/20 (0%)	0
Musculoskeletal and connective tissue disorders
Pain: Back	0/33 (0%)	0	1/20 (5%)	1
Pain: Bone	6/33 (18.2%)	6	0/20 (0%)	0
Pain: Extremity-limb	1/33 (3%)	1	0/20 (0%)	0
Pain NOS	3/33 (9.1%)	3	0/20 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	0/33 (0%)	0	1/20 (5%)	1
Skin and subcutaneous tissue disorders
Pruritus/itching	1/33 (3%)	1	0/20 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.