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

Refractory Multiple Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01074060
• Other study ID #: 08186
• Secondary ID: NCI-2010-00160
• Status: Completed
• Phase: Phase 1
• First received: February 19, 2010
• Last updated: February 13, 2013
• Start date: April 2010
• Est. completion date: February 2013

Study information

• Verified date: February 2013
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: February 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Refractory Multiple Myeloma
• Stage I Multiple Myeloma
• Stage II Multiple Myeloma
• Stage III Multiple Myeloma

Intervention

Drug:
• plerixafor
Given IV

Biological:
• filgrastim
Given SC

Drug:
• cyclophosphamide
Given IV

Procedure:
• autologous hematopoietic stem cell transplantation
autologous hematopoietic stem cell transplantation

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	City of Hope	Duarte	California

Sponsors (1)

Lead Sponsor	Collaborator
City of Hope Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		12 to 18 months	Yes
Primary	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.	6 months post transplant	Yes
Secondary	Frequency of collecting 5 x 10^6 or more CD34+ cells/kg in 2 or less apheresis days		5 days post apheresis completion	No
Secondary	Percentage of plasma cells		5 days post apheresis	No
Secondary	Completion of 100 days post-transplant		100 days post-transplant	No
Secondary	Overall and disease-free survival		6months and one year post transplant	No
Secondary	Time to engraftment		6 months post transplant	No