Hematologic Malignancies
Conditions
Keywords
Cyclophosphamide, Hematopoietic, Stem Cell, Mobilization, Hematologic Malignancy
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.
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.
Interventions
DRUGCyclophosphamide
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.
Sponsors
Dartmouth-Hitchcock Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Nucleated Cells Collected Within the Apheresis Products | 6 weeks | the investigator will identify the number of cells collected within the apheresis products |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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 |
| 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. |
| 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. |
Countries
United States
Participant flow
Pre-assignment details
58 Individuals provided informed consent. Of those. four (4) participants were screen failures.
Participants by arm
| Arm | Count |
|---|---|
| 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).
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. | 32 |
| 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).
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. | 20 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | No longer eligible | 2 | 0 |
Baseline characteristics
| Characteristic | Arm 1: 1.5 Gms/m(2) Cyclophosphamide | Total | Arm 2: Cyclophosphamide 3 Gms/m(2) |
|---|---|---|---|
| Age, Continuous | 62.5 years | 61.9 years | 61.3 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 32 Participants | 52 Participants | 20 Participants |
| Region of Enrollment United States | 32 participants | 52 participants | 20 participants |
| Sex: Female, Male Female | 11 Participants | 21 Participants | 10 Participants |
| Sex: Female, Male Male | 21 Participants | 31 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 33 | 0 / 20 |
| other Total, other adverse events | 16 / 33 | 8 / 20 |
| serious Total, serious adverse events | 1 / 33 | 2 / 20 |
Outcome results
Primary
Number of CD34+ Cells Collected Within the Apheresis Products
the investigator will identify the number of CD34+ cells collected within the apheresis products
Time frame: 6 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1: 1.5 Gms/m(2) Cyclophosphamide | Number of CD34+ Cells Collected Within the Apheresis Products | 7 cells x10e8 |
| Arm 2: Cyclophosphamide 3 Gms/m(2) | Number of CD34+ Cells Collected Within the Apheresis Products | 10.5 cells x10e8 |
Primary
Number of Nucleated Cells Collected Within the Apheresis Products
the investigator will identify the number of cells collected within the apheresis products
Time frame: 6 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1: 1.5 Gms/m(2) Cyclophosphamide | Number of Nucleated Cells Collected Within the Apheresis Products | 5.7 cells x10e10 |
| Arm 2: Cyclophosphamide 3 Gms/m(2) | Number of Nucleated Cells Collected Within the Apheresis Products | 3.8 cells x10e10 |
Secondary
Resource Utilization- Hospitalizations
Resources used during the mobilization and apheresis processes will be captured.
Time frame: participants will be followed approximately 6 weeks following initiation of treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1: 1.5 Gms/m(2) Cyclophosphamide | Resource Utilization- Hospitalizations | 1 Participants |
| Arm 2: Cyclophosphamide 3 Gms/m(2) | Resource Utilization- Hospitalizations | 1 Participants |
Secondary
Resource Utilization- Incidence of Febrile Neutropenia
Resources used during the mobilization and apheresis processes will be captured.
Time frame: participants will be followed approximately 6 weeks following initiation of treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1: 1.5 Gms/m(2) Cyclophosphamide | Resource Utilization- Incidence of Febrile Neutropenia | 2 Participants |
| Arm 2: Cyclophosphamide 3 Gms/m(2) | Resource Utilization- Incidence of Febrile Neutropenia | 2 Participants |
Secondary
Resource Utilization- Transfusion of Platelets
Resources used during the mobilization and apheresis processes will be captured.
Time frame: participants will be followed approximately 6 weeks following initiation of treatment
Population: 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.
Secondary
Resource Utilization - Transfusions of Red Blood Cells
Resources used during the mobilization and apheresis processes will be captured.
Time frame: participants will be followed approximately 6 weeks following initiation of treatment
Population: 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.
Secondary
Toxicities During the Mobilization and Apheresis Processes
Toxicities during the mobilization and apheresis processes Grade 3 and higher
Time frame: participants will be followed approximately 6 weeks following initiation of treatment
Population: Number of participants who experienced a grade 3 or higher adverse event
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1: 1.5 Gms/m(2) Cyclophosphamide | Toxicities During the Mobilization and Apheresis Processes | 4 Participants |
| Arm 2: Cyclophosphamide 3 Gms/m(2) | Toxicities During the Mobilization and Apheresis Processes | 7 Participants |