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Plerixafor and Filgrastim Following Cyclophosphamide for Stem Cell Mobilization in Patients With Multiple Myeloma

Primary Purpose

Refractory Multiple Myeloma, Stage I Multiple Myeloma, Stage II Multiple Myeloma

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

plerixafor

filgrastim

cyclophosphamide

autologous hematopoietic stem cell transplantation

laboratory biomarker analysis

About this trial

This is an interventional treatment trial for Refractory Multiple Myeloma

Eligibility Criteria

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

Criteria

Inclusion and exclusion criteria must be re-evaluated prior to dosing with PLERIXAFOR; if the patient does not meet any of these criteria (excluding the hepatic and hematologic criteria) the patient is not eligible to continue unless Genzyme grants a waiver

Inclusion

Eligible to undergo autologous transplantation
Diagnosed with multiple myeloma (MM)
ECOG (Eastern Cooperative Oncology Group) performance status of 0 or 1
The patient has recovered from all acute toxic effects of prior chemotherapy
White Blood Count (WBC) > 2.5 x 10^9/L
Absolute neutrophil count >1.5 x 10^9/L
Platelet count > 100 x 10^9/L
Serum creatinine <= 2.5 mg/dl
Creatinine clearance >= 50 ml/min (measured or calculated)
Serum glutamic oxaloacetic transaminase (SGOT) < 2 x ULN (Upper Limit of Normal)
Serum glutamic pyruvic transaminase (SGPT) < 2 x ULN
Total bilirubin < 2 x ULN
Left ventricle ejection fraction > 45% [by normal ECHO (Echocardiogram) or MUGA (MUltiple Gated Acquisition) scan]
FEV1 (forced expiratory volume in 1 second) > 60% of predicted or DLCO (Carbon Monoxide Diffusing Capacity )> 55% of predicted
No active infection of hepatitis B or C
Negative for HIV
Signed informed consent (may be obtained anytime prior to admission for cytoxan)
Women of child bearing potential agree to use an approved form of contraception

Exclusion

A co-morbid condition which, in the view of the investigators, renders the patient at high risk from treatment complications
A residual acute medical condition resulting from prior chemotherapy
Brain metastases or carcinomatous meningitis
Acute infection
Fever (temp > 38 degrees C/100.4 degrees F)
Positive pregnancy test in female patients
Lactating females
Patients of child-bearing potential unwilling to implement adequate birth control
Prior treatment with Plerixafor
Prior stem cell transplant, either autologous or allogeneic
Prior cyclophosphamide priming
Heart rate < 50 at screening
Abnormal ECG (electrocardiogram) with a clinically significant rhythm disturbance or conduction abnormality that in the opinion of the investigator warrants exclusion of the subject from the trial
Patients with congestive heart failure at screening
History of atrial fibrillation
Patients who are currently on medication to control cardiac arrhythmias

Sites / Locations

City of Hope

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm I

Arm Description

MOBILIZATION: Patients receive cyclophosphamide IV. Patients also receive filgrastim subcutaneously (SC) daily beginning approximately 24 hours later. TREATMENT/APHERESIS: Beginning 10 days after cyclophosphamide, patients receive plerixafor IV over 30 minutes followed by filgrastim SC on each day of apheresis.

Outcomes

Primary Outcome Measures

To assess the MTD ( maximum tolerated dose) of IV plerixafor when given post cyclophosphamide and GCSF for stem cell priming.Dose limiting toxicity will be defined as any grade 3 or 4 nonhematologic toxicity.

Tolerability and safety of PLERIXAFOR

Will be summarized in terms of type, severity (by National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v4.0), date of onset, duration, reversibility, and attribution.

Secondary Outcome Measures

Frequency of collecting 5 x 10^6 or more CD34+ cells/kg in 2 or less apheresis days

Percentage of plasma cells

Completion of 100 days post-transplant

Overall and disease-free survival

Time to engraftment

Full Information

NCT ID

NCT01074060

First Posted

February 19, 2010

Last Updated

February 13, 2013

Sponsor

City of Hope Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT01074060

Brief Title

Plerixafor and Filgrastim Following Cyclophosphamide for Stem Cell Mobilization in Patients With Multiple Myeloma

Official Title

A Phase I/Pilot Study of Intravenous PLERIXAFOR Following Cyclophosphamide Mobilization in Patients With Multiple Myeloma

Study Type

Interventional

2. Study Status

Record Verification Date

February 2013

Overall Recruitment Status

Completed

Study Start Date

April 2010 (undefined)

Primary Completion Date

February 2013 (Actual)

Study Completion Date

February 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

City of Hope Medical Center

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

RATIONALE: There are different methods of stem cell mobilization, such as using colony-stimulating factors alone or following chemotherapy priming. More recently, the combination of plerixafor and colony-stimulating factors has been shown to enhance stem cell mobilization. This study will assess whether the combination of plerixafor and Granulocyte Colony-Stimulating Factor (G-CSF) is effective following chemotherapy mobilization with cyclophosphamide. PURPOSE: To assess the safety, tolerability, and best dose of intravenous plerixafor following cyclophosphamide priming.

Detailed Description

PRIMARY OBJECTIVES: I. To assess the safety and tolerability of intravenous(IV) PLERIXAFOR when given in combination with cyclophosphamide and G-CSF as a mobilization regimen in patients with Multiple Myeloma. SECONDARY OBJECTIVES: I. To determine if intravenous PLERIXAFOR, given with a cyclophosphamide and G-CSF mobilizing regimen, will allow collection of greater than or equal to 5 x 10^6 CD34+ cells/kg in 2 or less apheresis days. II. To review the timing of intravenous plerixafor administration prior to apheresis and describe our experience. OUTLINE: MOBILIZATION: Patients receive cyclophosphamide intravenously (IV). Patients also receive filgrastim subcutaneously (SC) daily beginning approximately 24 hours later. TREATMENT/APHERESIS: Beginning 10 days after cyclophosphamide, patients receive plerixafor IV over 30 minutes followed by filgrastim SC on each day of apheresis. Following the collection of an adequate number of stem cells, patients undergo high-dose chemotherapy and autologous stem cell rescue. Patients are followed post-autologous stem cell transplant for engraftment. After completion of study treatment, patients are followed periodically.

6. Conditions and Keywords

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

Refractory Multiple Myeloma, Stage I Multiple Myeloma, Stage II Multiple Myeloma, Stage III Multiple Myeloma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

18 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm I

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

plerixafor

Other Intervention Name(s)

AMD 3100, LM-3100, Mozobil

Intervention Description

Given IV

Intervention Type

Biological

Intervention Name(s)

filgrastim

Other Intervention Name(s)

G-CSF, granulocyte colony-stimulating factor, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor

Intervention Description

Given SC

Intervention Type

Drug

Intervention Name(s)

cyclophosphamide

Other Intervention Name(s)

CPM, CTX, Cytoxan, Endoxan, Endoxana, Enduxan

Intervention Description

Given IV

Intervention Type

Procedure

Intervention Name(s)

autologous hematopoietic stem cell transplantation

Intervention Description

autologous hematopoietic stem cell transplantation

Intervention Type

Other

Intervention Name(s)

laboratory biomarker analysis

Intervention Description

Correlative studies

Primary Outcome Measure Information:

Title

Time Frame

12 to 18 months

Title

Tolerability and safety of PLERIXAFOR

Description

Will be summarized in terms of type, severity (by National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v4.0), date of onset, duration, reversibility, and attribution.

Time Frame

6 months post transplant

Secondary Outcome Measure Information:

Title

Frequency of collecting 5 x 10^6 or more CD34+ cells/kg in 2 or less apheresis days

Time Frame

5 days post apheresis completion

Title

Percentage of plasma cells

Time Frame

5 days post apheresis

Title

Completion of 100 days post-transplant

Time Frame

100 days post-transplant

Title

Overall and disease-free survival

Time Frame

6months and one year post transplant

Title

Time to engraftment

Time Frame

6 months post transplant

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Criteria Inclusion and exclusion criteria must be re-evaluated prior to dosing with PLERIXAFOR; if the patient does not meet any of these criteria (excluding the hepatic and hematologic criteria) the patient is not eligible to continue unless Genzyme grants a waiver Inclusion Eligible to undergo autologous transplantation Diagnosed with multiple myeloma (MM) ECOG (Eastern Cooperative Oncology Group) performance status of 0 or 1 The patient has recovered from all acute toxic effects of prior chemotherapy White Blood Count (WBC) > 2.5 x 10^9/L Absolute neutrophil count >1.5 x 10^9/L Platelet count > 100 x 10^9/L Serum creatinine <= 2.5 mg/dl Creatinine clearance >= 50 ml/min (measured or calculated) Serum glutamic oxaloacetic transaminase (SGOT) < 2 x ULN (Upper Limit of Normal) Serum glutamic pyruvic transaminase (SGPT) < 2 x ULN Total bilirubin < 2 x ULN Left ventricle ejection fraction > 45% [by normal ECHO (Echocardiogram) or MUGA (MUltiple Gated Acquisition) scan] FEV1 (forced expiratory volume in 1 second) > 60% of predicted or DLCO (Carbon Monoxide Diffusing Capacity )> 55% of predicted No active infection of hepatitis B or C Negative for HIV Signed informed consent (may be obtained anytime prior to admission for cytoxan) Women of child bearing potential agree to use an approved form of contraception Exclusion A co-morbid condition which, in the view of the investigators, renders the patient at high risk from treatment complications A residual acute medical condition resulting from prior chemotherapy Brain metastases or carcinomatous meningitis Acute infection Fever (temp > 38 degrees C/100.4 degrees F) Positive pregnancy test in female patients Lactating females Patients of child-bearing potential unwilling to implement adequate birth control Prior treatment with Plerixafor Prior stem cell transplant, either autologous or allogeneic Prior cyclophosphamide priming Heart rate < 50 at screening Abnormal ECG (electrocardiogram) with a clinically significant rhythm disturbance or conduction abnormality that in the opinion of the investigator warrants exclusion of the subject from the trial Patients with congestive heart failure at screening History of atrial fibrillation Patients who are currently on medication to control cardiac arrhythmias

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Amrita Krishnan

Organizational Affiliation

City of Hope Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

City of Hope

City

Duarte

State/Province

California

ZIP/Postal Code

91010

Country

United States

12. IPD Sharing Statement

Learn more about this trial

Plerixafor and Filgrastim Following Cyclophosphamide for Stem Cell Mobilization in Patients With Multiple Myeloma

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