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

NCT ID: NCT02139280

Last Updated: 2021-02-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-12-31
• Study Completion Date: 2020-09-30

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.

Conditions

Hematologic Malignancies

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: ACTIVE_COMPARATOR

Cyclophosphamide

Intervention Type: DRUG

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.

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).

Group Type: EXPERIMENTAL

Cyclophosphamide

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Endoxan; Cytoxan; Neosar; Procytox; Revimmune; Cytophosphane

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Dartmouth-Hitchcock Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Kenneth Meehan

Director, Bone Marrow Transplant Program

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kenneth Meehan, MD

Role: PRINCIPAL_INVESTIGATOR

Dartmouth-Hitchcock Medical Center

Locations

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

D13179

Identifier Type: -

Identifier Source: org_study_id