AMD3100 (Plerixafor) With G-CSF in Poor Mobilizing Adult Patients Who Previously Failed Hematopoietic Stem Cell (HSC) Collection/Attempts

NCT00396331 | Completed Phase 2 Results

• 1 other identifier: AMD31002112
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 8

Brief Summary

This study evaluates the safety, efficacy, and pharmacokinetics (PK) 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 who would benefit from an autologous stem cell transplant but have failed previous collections or collection attempts with a mobilization regimen of G-CSF alone, chemotherapy and G-CSF, or any other conventional therapy including cytokines, chemotherapy and cytokines and bone marrow harvests. The only change to standard of care of a mobilization regimen that includes G-CSF is the addition of a dose of AMD3100 (plerixafor) on the evening prior to each day of apheresis. Efficacy outcomes include quantification of CD34+ cells in the apheresis product and assessment of successful polymorphonuclear leukocyte (PMN) and platelet (PLT) engraftment after transplantation. PK outcomes include analysis of repeated doses of plerixafor.

Conditions

Autologous Stem Cell Transplantation

Keywords

Multiple Myeloma; Non-Hodgkin's Lymphoma; autologous transplantation; AMD3100; stem cell mobilization; plerixafor

Outcome Measures

Primary Outcomes (3)

• Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period

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

  Day 1 to approximately day 38

• Proportion of Participants Who Achieved ≥2*10^6 CD34+ Cells/kg Following Treatment With Plerixafor and G-CSF

  Proportion of participants who reached the target of at least 2\*10\^6 CD34+ cells/kg collected during up to 7 aphereses.

  Day 5 to Day 11 (up to 7 apheresis)

• Proportion of Participants Who Achieved ≥5*10^6 CD34+ Cells/kg Following Treatment With Plerixafor and G-CSF

  Proportion of participants who reached the target of at least 5\*10\^6 CD34+ cells/kg collected during up to 7 apheresis.

  Day 5 to Day 11 (up to 7 aphereses)

Secondary Outcomes (12)

• Median Number of Days to Polymorphonuclear Leukocyte (PMN) Engraftment

  approximately 2 months (1 month post transplant)

• Median Number of Days to Platelet (PLT) Engraftment

  Approximately 2 months (1 month post transplant)

• Number of Participants With Durable Engraftment 12 Months After Autologous Transplantation

  Approximately 13 months (12 months post transplant )

• Number of Participants With Non-Hodgkin's Lymphoma (NHL) Who Had Evidence of Tumor Cell Mobilization After G-CSF or Plerixafor Administration

  Up to Day 7

• Number of Participants Who Achieved ≥2*10^6 CD34+ Cells/kg Collected During Both Courses of Treatment With Plerixafor and G-CSF

  Day 5 up to Month 6 (up to 7 aphereses in each course of treatment)

Study Arms (1)

G-CSF plus Plerixafor

EXPERIMENTAL

Drug: G-CSF plus plerixafor

Interventions

G-CSF plus plerixafor DRUG

Participants underwent mobilization with granulocyte colony-stimulating factor (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 7 aphereses or until ≥ 2\*10\^6 CD34+ cells/kg were collected.

Also known as: AMD3100, Mozobil

G-CSF plus Plerixafor

Eligibility Criteria

• Age: 18 Years - 78 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eligible to undergo autologous transplantation
• Has failed previous collections or collection attempts with a mobilization regimen of granulocyte colony-stimulating factor (G-CSF), chemotherapy and G-CSF or any other conventional therapy including cytokines, chemotherapy and cytokines or bone marrow harvest.
• Eastern Co-operative Oncology Group (ECOG) performance status of 0 or 1

You may not qualify if:

• The patient has recovered from all acute toxic effects of prior chemotherapy
• White blood cell count (WBC) \>2.5\*10\^9/L
• Absolute neutrophil count \>1.5\*10\^9/L
• Platelet count \>85\*10\^9/L
• Serum creatinine ≤1.5 mg/dl
• Creatinine clearance \>60 ml/min
• Aspartate aminotransferase (AST), alanine transaminase (ALT) and total bilirubin \<2x upper limit of normal (ULN)
• Left ventricle ejection fraction \>45% (by normal echocardiogram (ECHO) or multiple gated acquisition (MUGA) scan)
• Forced expiratory volume in one minute (FEV1) \>60% of predicted or diffusion lung capacity for carbon monoxide (DLCO) ≥45% of predicted
• No active infection of hepatitis B or C
• Negative for HIV
• Signed informed consent
• Women of child-bearing potential agree to use an approved form of contraception
• Once 70 patients have enrolled, patients with diagnoses other than lymphoma are not eligible (eg, acute myeloid leukemia, chronic lymphocytic leukemia, or multiple myeloma).
• A co-morbid condition which, in the view of the investigators, renders the patient at high risk from treatment complications

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead

Study Sites (8)

City of Hope National Medical Center'

Duarte, California, 91010, United States

Location

H. Lee Moffitt Cancer Center

Tampa, Florida, 33612-9497, United States

Location

Blood & Marrow Transplant Group of Georgia

Atlanta, Georgia, 30342, United States

Location

University of Mississippi Medical Center, Div of Hematology

Jackson, Mississippi, 39216, United States

Location

Kansas City Cancer Centers

Kansas City, Missouri, 64111, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Virginia Commonwealth University - Massey Cancer Center

Richmond, Virginia, 23298-0037, United States

Location

University of Wisconsin, Blood and Bone Marrow Transplant

Madison, Wisconsin, 53792-5156, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Lymphoma, Non-Hodgkin

Interventions

Granulocyte Colony-Stimulating Factor; plerixafor

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Lymphoma; Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Medical Monitor
• Organization: Genzyme

medinfo@genzyme.com

Study Officials

• Medical Monitor

  Genzyme, a Sanofi Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2006
• First Posted: November 6, 2006
• Study Start: October 1, 2005
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: March 13, 2014
• Results First Posted: December 2, 2010

Record last verified: 2014-02

Locations

US (8)