Clinical trial NCT01074060: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Refractory Multiple Myeloma
Stage I Multiple Myeloma
Stage II Multiple Myeloma
Stage III Multiple Myeloma
Lead sponsor: City of Hope Medical Center
Sponsor class: OTHER
First posted: 2010-02-24
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: 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.
timeFrame: 12 to 18 months
measure: Tolerability and safety of PLERIXAFOR
timeFrame: 6 months post transplant
Secondary outcomes:
measure: Frequency of collecting 5 x 10^6 or more CD34+ cells/kg in 2 or less apheresis days
timeFrame: 5 days post apheresis completion
measure: Percentage of plasma cells
timeFrame: 5 days post apheresis
measure: Completion of 100 days post-transplant
timeFrame: 100 days post-transplant
measure: Overall and disease-free survival
timeFrame: 6months and one year post transplant
measure: Time to engraftment
timeFrame: 6 months post transplant
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
Study officials:
affiliation: City of Hope Medical Center
name: Amrita Krishnan
role: PRINCIPAL_INVESTIGATOR
References: