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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT01074060
First received: February 19, 2010
Last updated: February 13, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Refractory Multiple Myeloma
Stage I Multiple Myeloma
Stage II Multiple Myeloma
Stage III Multiple Myeloma
Drug: plerixafor
Biological: filgrastim
Drug: cyclophosphamide
Procedure: autologous hematopoietic stem cell transplantation
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/Pilot Study of Intravenous PLERIXAFOR Following Cyclophosphamide Mobilization in Patients With Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

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. [ Time Frame: 12 to 18 months ] [ Designated as safety issue: Yes ]
  • Tolerability and safety of PLERIXAFOR [ Time Frame: 6 months post transplant ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 5 days post apheresis completion ] [ Designated as safety issue: No ]
  • Percentage of plasma cells [ Time Frame: 5 days post apheresis ] [ Designated as safety issue: No ]
  • Completion of 100 days post-transplant [ Time Frame: 100 days post-transplant ] [ Designated as safety issue: No ]
  • Overall and disease-free survival [ Time Frame: 6months and one year post transplant ] [ Designated as safety issue: No ]
  • Time to engraftment [ Time Frame: 6 months post transplant ] [ Designated as safety issue: No ]

Enrollment: 18
Study Start Date: April 2010
Study Completion Date: February 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I

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.

Drug: plerixafor
Given IV
Other Names:
  • AMD 3100
  • LM-3100
  • Mozobil
Biological: filgrastim
Given SC
Other Names:
  • G-CSF
  • granulocyte colony-stimulating factor
  • Neupogen
  • r-metHuG-CSF
  • Recombinant Methionyl Human Granulocyte Colony Stimulating Factor
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
  • Enduxan
Procedure: autologous hematopoietic stem cell transplantation
autologous hematopoietic stem cell transplantation
Other: laboratory biomarker analysis
Correlative studies

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

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01074060

Locations
United States, California
City of Hope
Duarte, California, United States, 91010
Sponsors and Collaborators
City of Hope Medical Center
Investigators
Principal Investigator: Amrita Krishnan Beckman Research Institute
  More Information

No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT01074060     History of Changes
Other Study ID Numbers: 08186, NCI-2010-00160
Study First Received: February 19, 2010
Last Updated: February 13, 2013
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
Cyclophosphamide
JM 3100
Lenograstim
Adjuvants, Immunologic
Alkylating Agents
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Antiviral Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists

ClinicalTrials.gov processed this record on October 23, 2014