Mobilization of Stem Cells With AMD3100 (Plerixafor) and G-CSF in Non-Hodgkin's Lymphoma and Multiple Myeloma Patients

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Primary Purpose

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

G-CSF Plus Plerixafor

About this trial

This is an interventional treatment trial for Lymphoma, Non-Hodgkin focused on measuring Non-Hodgkin's Lymphoma, Multiple Myeloma, Stem cell mobilization

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Diagnosis of non-Hodgkin's lymphoma (NHL) or multiple myoloma (MM) eligible for autologous transplantation No more than 3 prior regimens of chemotherapy More than 4 weeks since last cycle of chemotherapy. Patient recovered from all acute toxic effects of prior chemotherapy. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 White blood cell (WBC) count >3.0*10^9/L Absolute polymorphonuclear cells (PMN) count >1.5*10^9/L Platelet (PLT) count >100*10^9/L Serum creatinine <=2.2 mg/dL Serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) and total bilirubin <2 x upper limit of normal (ULN) Left ventricle ejection fraction >45% by normal echocardiogram or multiple-gated acquisition (MUGA) scan Forced expiratory volume of the lung in the first second (FEV1) >60% of predicted or diffusing capacity of the lung for carbon monoxide (DLCO) >45% of predicted Negative for human immunodeficiency virus (HIV) type 1 Women of child bearing potential agreed to use an approved form of contraception. Exclusion Criteria: Patients who have failed previous collections Brain metastases or carcinomatous meningitis History of ventricular arrhythmias A co-morbid condition which, in the view of the investigator, renders the patient at high risk for treatment complications A residual acute medical condition resulting from prior chemotherapy Acute infection Fever (temp >38°C/100.4°F) Patients whose actual body weight exceeds 175% of their ideal body weight Patients who previously received experimental therapy within 4 weeks of enrolling in this study or who are currently enrolled in another experimental study during the mobilization period Positive pregnancy test in female patients Lactating females Patients of child-bearing potential unwilling to implement adequate birth control. Patients who have deterioration of their clinical status or laboratory parameters between the time of enrolment and transplant (such that they no longer meet entry criteria) may be removed from study at the discretion of the treating physician, principal investigator, or sponsor.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Non-Hodgkin's Lymphoma (NHL)

Multiple Myeloma (MM)

Arm Description

Participants with NHL were mobilized with granulocyte colony-stimulating factor (G-CSF) 10 µg/kg/day for 4 days. Plerixafor 240 µg/kg was given the evening of day 4 and G-CSF given the next morning followed by apheresis. Evening doses of plerixafor and morning doses of G-CSF followed by apheresis continued for up to a maximum of 5 aphereses or until ≥ 5*10^6 CD34+ cells/kg were collected.

Participants with MM were mobilized with granulocyte colony-stimulating factor (G-CSF) 10 µg/kg/day for 4 days. Plerixafor 240 µg/kg was given the evening of day 4 and G-CSF given the next morning followed by apheresis. Evening doses of plerixafor and morning doses of G-CSF followed by apheresis continued for up to a maximum of 5 aphereses or until ≥ 5*10^6 CD34+ cells/kg were collected.

Outcomes

Primary Outcome Measures

Number of Participants in Overall Safety Summary of Treatment Emergent Adverse Events (TEAE)

Number of participants with treatment emergent adverse events (TEAEs) collected from Day 1 (start of G-CSF mobilization) to the day before starting chemotherapy (approximately day 38). AEs were graded by the investigator using the World Health Organization (WHO) Adverse Event Grading Scale and were assessed for severity (mild, moderate, severe) and relatedness to study treatment (5 point scale from 'not related' to 'definitely related').

Secondary Outcome Measures

Number of Participants Achieving a Two-Fold (Relative) Increase in Peripheral Blood (PB) CD34+ Cells/µL Following the First Dose of Plerixafor

The number of participants mobilized with G-CSF + plerixafor injection who have a ≥ 2-fold increase in CD34+ cells. Fold increase was expressed as a ratio. Fold increase = (pre-apheresis PB CD34+ cells/µL) / (pre-plerixafor dosing PB CD34+ cells/µL)

Number of Transplants in Which Participants Achieved Polymorphonuclear Leukocyte (PMN) Engraftment by Day 12 But No Later Than Day 21 Post Peripheral Blood Stem Cell (PBSC) Transplant

Participants were monitored for polymorphonuclear leukocyte (PMN) engraftment as per the local standard of care. The target for engraftment was 12 days after PBSC transplant and no transplant taking longer than 21 days for engraftment.

Full Information

NCT ID

NCT00322491

First Posted

May 4, 2006

Last Updated

February 10, 2014

Sponsor

Genzyme, a Sanofi Company

Collaborators

AnorMED

1. Study Identification

Unique Protocol Identification Number

NCT00322491

Brief Title

Mobilization of Stem Cells With AMD3100 (Plerixafor) and G-CSF in Non-Hodgkin's Lymphoma and Multiple Myeloma Patients

Official Title

Treatment With AMD3100 in Non-Hodgkin's Lymphoma and Multiple Myeloma Patients to Increase the Number of Peripheral Blood Stem Cells When Given a Mobilizing Regimen of G-CSF

Study Type

Interventional

2. Study Status

Record Verification Date

February 2014

Overall Recruitment Status

Completed

Study Start Date

March 2004 (undefined)

Primary Completion Date

June 2006 (Actual)

Study Completion Date

June 2006 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

Genzyme, a Sanofi Company

Collaborators

AnorMED

4. Oversight

Data Monitoring Committee

No

5. Study Description

Brief Summary

This study evaluates the safety and efficacy of plerixafor given in addition to granulocyte-colony stimulating factor (G-CSF) for collection of peripheral blood stem cells (PBSCs) for autologous transplantation in patients with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM). Efficacy outcomes include evaluation of fold increase in circulating CD34+ cells from just before the first plerixafor injection to 10-11 hours post plerixafor (just before apheresis) and assessment of successful polymorphonuclear leukocyte (PMN) engraftment after transplantation. Data from this protocol will assist in the determination of the dosing schedule for future studies.

Detailed Description

Participants with NHL and MM who have undergone prior cyto-reductive chemotherapy, are to be autologously transplanted, and meet the inclusion/exclusion criteria are eligible to enter the study. The only change to the standard of care is the addition of plerixafor to a granulocyte colony-stimulating factor (G-CSF) mobilization regimen on the day prior to apheresis. Participants will undergo mobilization with G-CSF (10 mcg/kg each day) and will receive plerixafor (240 mcg/kg) in the evening prior to apheresis. Participants will undergo apheresis for up to 5 consecutive days in order to collect the target number of CD34+ stem cells (≥ 5*10^6 CD34+ cells/kg for either single or tandem transplant). After apheresis, all participants will be treated with high-dose chemotherapy in preparation for transplantation. Participants will be transplanted with cells obtained from the G-CSF and plerixafor mobilization regimen. The increase in CD34+ cells in the peripheral blood from the time of the plerixafor dose to just prior to apheresis and the number of CD34+ cells in the apheresis product will be measured. The number of apheresis sessions required to obtain ≥ 5*10^6 CD34+ cells will also be measured. Success of the transplantation(s) will be evaluated by the time to engraftment of polymorphonuclear leukocytes (PMN) and platelets (PLT). Participants will be followed for durability of their transplant for 12 months following transplantation. This study was previously posted by AnorMED, Inc. In November 2006, AnorMED, Inc. was acquired by Genzyme Corporation. Genzyme Corporation is the sponsor of the trial.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lymphoma, Non-Hodgkin, Multiple Myeloma

Keywords

Non-Hodgkin's Lymphoma, Multiple Myeloma, Stem cell mobilization

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

49 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Non-Hodgkin's Lymphoma (NHL)

Arm Type

Experimental

Arm Description

Participants with NHL were mobilized with granulocyte colony-stimulating factor (G-CSF) 10 µg/kg/day for 4 days. Plerixafor 240 µg/kg was given the evening of day 4 and G-CSF given the next morning followed by apheresis. Evening doses of plerixafor and morning doses of G-CSF followed by apheresis continued for up to a maximum of 5 aphereses or until ≥ 5*10^6 CD34+ cells/kg were collected.

Arm Title

Multiple Myeloma (MM)

Arm Type

Experimental

Arm Description

Participants with MM were mobilized with granulocyte colony-stimulating factor (G-CSF) 10 µg/kg/day for 4 days. Plerixafor 240 µg/kg was given the evening of day 4 and G-CSF given the next morning followed by apheresis. Evening doses of plerixafor and morning doses of G-CSF followed by apheresis continued for up to a maximum of 5 aphereses or until ≥ 5*10^6 CD34+ cells/kg were collected.

Intervention Type

Drug

Intervention Name(s)

G-CSF Plus Plerixafor

Other Intervention Name(s)

AMD3100, Mozobil

Intervention Description

Participants underwent mobilization with G-CSF 10 µg/kg/day for 4 days, administered by subcutaneous injection (SC) injection each morning. On the evening of Day 4, participants received a dose of plerixafor 240 µg/kg, administered by SC injection. On Day 5, participants returned to the clinic and received a morning dose of G-CSF 10 µg/kg and underwent apheresis approximately 10 to 11 hours after the dose of plerixafor (within 60 minutes after administration of G-CSF). Participants continued to receive an evening dose of plerixafor followed the next day by a morning dose of G-CSF and apheresis for up to a maximum of 5 aphereses or until ≥ 5*10^6 CD34+ cells/kg were collected.

Primary Outcome Measure Information:

Title

Number of Participants in Overall Safety Summary of Treatment Emergent Adverse Events (TEAE)

Description

Number of participants with treatment emergent adverse events (TEAEs) collected from Day 1 (start of G-CSF mobilization) to the day before starting chemotherapy (approximately day 38). AEs were graded by the investigator using the World Health Organization (WHO) Adverse Event Grading Scale and were assessed for severity (mild, moderate, severe) and relatedness to study treatment (5 point scale from 'not related' to 'definitely related').

Time Frame

Day 1 to approximately Day 38 (before start of chemotherapy)

Secondary Outcome Measure Information:

Title

Number of Participants Achieving a Two-Fold (Relative) Increase in Peripheral Blood (PB) CD34+ Cells/µL Following the First Dose of Plerixafor

Description

The number of participants mobilized with G-CSF + plerixafor injection who have a ≥ 2-fold increase in CD34+ cells. Fold increase was expressed as a ratio. Fold increase = (pre-apheresis PB CD34+ cells/µL) / (pre-plerixafor dosing PB CD34+ cells/µL)

Time Frame

Days 4-5 (first dose of plerixafor to apheresis)

Title

Number of Transplants in Which Participants Achieved Polymorphonuclear Leukocyte (PMN) Engraftment by Day 12 But No Later Than Day 21 Post Peripheral Blood Stem Cell (PBSC) Transplant

Description

Participants were monitored for polymorphonuclear leukocyte (PMN) engraftment as per the local standard of care. The target for engraftment was 12 days after PBSC transplant and no transplant taking longer than 21 days for engraftment.

Time Frame

2 months

Other Pre-specified Outcome Measures:

Title

Median Cumulative Number of CD34+ Cells Collected During Apheresis

Description

Median cumulative total number of CD34+ cells collected during apheresis.

Time Frame

Days 5-8

Title

Number of Transplants in Which Participants Achieved Platelet (PLT) Engraftment by Day 12 But No Later Than Day 21 Post Peripheral Blood Stem Cell (PBSC) Transplant

Description

Participants were monitored for platelet (PLT) engraftment as per the local standard of care. The target for engraftment was 12 days after PBSC transplant and no transplant taking longer than 21 days for engraftment.

Time Frame

2 months

Title

Number of Participants With Durable Engraftment 12 Months After Transplantation

Description

The number of participants maintaining a durable graft 12 months after autologous transplantation. A durable graft is defined as the maintenance of normal blood counts.

Time Frame

Approximately 13 months (12 months post-transplant )

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria: Diagnosis of non-Hodgkin's lymphoma (NHL) or multiple myoloma (MM) eligible for autologous transplantation No more than 3 prior regimens of chemotherapy More than 4 weeks since last cycle of chemotherapy. Patient recovered from all acute toxic effects of prior chemotherapy. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 White blood cell (WBC) count >3.0*10^9/L Absolute polymorphonuclear cells (PMN) count >1.5*10^9/L Platelet (PLT) count >100*10^9/L Serum creatinine <=2.2 mg/dL Serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) and total bilirubin <2 x upper limit of normal (ULN) Left ventricle ejection fraction >45% by normal echocardiogram or multiple-gated acquisition (MUGA) scan Forced expiratory volume of the lung in the first second (FEV1) >60% of predicted or diffusing capacity of the lung for carbon monoxide (DLCO) >45% of predicted Negative for human immunodeficiency virus (HIV) type 1 Women of child bearing potential agreed to use an approved form of contraception. Exclusion Criteria: Patients who have failed previous collections Brain metastases or carcinomatous meningitis History of ventricular arrhythmias A co-morbid condition which, in the view of the investigator, renders the patient at high risk for treatment complications A residual acute medical condition resulting from prior chemotherapy Acute infection Fever (temp >38°C/100.4°F) Patients whose actual body weight exceeds 175% of their ideal body weight Patients who previously received experimental therapy within 4 weeks of enrolling in this study or who are currently enrolled in another experimental study during the mobilization period Positive pregnancy test in female patients Lactating females Patients of child-bearing potential unwilling to implement adequate birth control. Patients who have deterioration of their clinical status or laboratory parameters between the time of enrolment and transplant (such that they no longer meet entry criteria) may be removed from study at the discretion of the treating physician, principal investigator, or sponsor.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Monitor

Organizational Affiliation

Genzyme, a Sanofi Company

Official's Role

Study Director

Facility Information:

Facility Name

University of Arkansas for Medical Sciences

City

Little Rock

State/Province

Arkansas

Country

United States

Facility Name

UCLA School of Medicine

City

Loa Angeles

State/Province

California

Country

United States

Facility Name

Loyola University Medical Center

City

Maywood

State/Province

Illinois

Country

United States

Facility Name

University of Iowa

City

Iowa City

State/Province

Iowa

Country

United States

Facility Name

University of Minnesota

City

Minneapolis

State/Province

Minnesota

Country

United States

Facility Name

Mayo Clinic

City

Rochester

State/Province

Minnesota

Country

United States

Facility Name

Roswell Park Cancer Institute

City

Buffalo

State/Province

New York

Country

United States

Facility Name

Thomas Jefferson University

City

Philadelphia

State/Province

Pennsylvania

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

19167685

Citation

Stiff P, Micallef I, McCarthy P, Magalhaes-Silverman M, Weisdorf D, Territo M, Badel K, Calandra G. Treatment with plerixafor in non-Hodgkin's lymphoma and multiple myeloma patients to increase the number of peripheral blood stem cells when given a mobilizing regimen of G-CSF: implications for the heavily pretreated patient. Biol Blood Marrow Transplant. 2009 Feb;15(2):249-56. doi: 10.1016/j.bbmt.2008.11.028.

Results Reference

result

Lymphoma, Non-Hodgkin, Multiple Myeloma

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial