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

A Prospective Randomized Trial Examining Low- or Intermediate-Dose Cyclophosphamide for Hematopoietic Stem Cell Mobilization in Patients With a Hematologic Malignancy

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.

Study Overview

• Status: Completed
• Conditions: Hematologic Malignancies
• Intervention / Treatment: Drug: Cyclophosphamide

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 Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / 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: Cytoxan; Endoxan; Cytophosphane; Neosar; Revimmune; Procytox
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: Cytoxan; Endoxan; Cytophosphane; Neosar; Revimmune; Procytox

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resource Utilization - Transfusions of Red Blood Cells	Resources used during the mobilization and apheresis processes will be captured.	participants will be followed approximately 6 weeks following initiation of treatment
Resource Utilization- Transfusion of Platelets	Resources used during the mobilization and apheresis processes will be captured.	participants will be followed approximately 6 weeks following initiation of treatment
Resource Utilization- Hospitalizations	Resources used during the mobilization and apheresis processes will be captured.	participants will be followed approximately 6 weeks following initiation of treatment
Resource Utilization- Incidence of Febrile Neutropenia	Resources used during the mobilization and apheresis processes will be captured.	participants will be followed approximately 6 weeks following initiation of treatment
Toxicities During the Mobilization and Apheresis Processes	Toxicities during the mobilization and apheresis processes Grade 3 and higher	participants will be followed approximately 6 weeks following initiation of treatment

Collaborators and Investigators

• Sponsor: Dartmouth-Hitchcock Medical Center

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (ACTUAL): July 1, 2019
• Study Completion (ACTUAL): September 1, 2020

Study Registration Dates

• First Submitted: March 3, 2014
• First Submitted That Met QC Criteria: May 13, 2014
• First Posted (ESTIMATE): May 15, 2014

Study Record Updates

• Last Update Posted (ACTUAL): February 16, 2021
• Last Update Submitted That Met QC Criteria: January 28, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Cyclophosphamide; Hematopoietic; Hematologic Malignancy; Stem Cell; Mobilization
• Additional Relevant MeSH Terms: Neoplasms by Site; Hematologic Diseases; Neoplasms; Hematologic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide
• Other Study ID Numbers: D13179