Treatment With AMD3100 (Plerixafor) in Non-Hodgkin's Lymphoma and Multiple Myeloma Patients

NCT00322842 | Completed Phase 2 Results

• 1 other identifier: AMD3100-EU21
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 3

Brief Summary

This study evaluates the safety of plerixafor and other outcomes that are purely exploratory in nature. One other pre-specified outcome is to evaluate an interval of 10-11 hours between dosing with plerixafor and the beginning of apheresis to determine if there will be at least a 2-fold increase in circulating CD34+ cells. Data from this protocol will assist in the determination of the dosing schedule for future studies.

Conditions

Lymphoma, Non-Hodgkin; Multiple Myeloma

Keywords

Non-Hodgkin's lymphoma; Multiple Myeloma; Stem cell mobilization

Outcome Measures

Primary Outcomes (1)

• Number of Participants in Overall Safety Summary of Treatment Emergent Adverse Events (TEAE)

  Number of participants with treatment emergent adverse events (TEAEs) collected from Day 1 (start of G-CSF mobilization) to the day before starting chemotherapy (approximately day 38). AEs were graded by the investigator using the World Health Organization (WHO) Adverse Event Grading Scale and were assessed for severity (mild, moderate, severe) and relatedness to study treatment (5 step scale from 'not related' to 'definitely related').

  Day 1 to approximately Day 38 (before start of chemotherapy)

Secondary Outcomes (3)

• Fold (i.e., Relative) Increase in Peripheral Blood (PB) CD34+ Cells/µL After First Dose of Plerixafor

  Days 4-5 (first dose of plerixafor to apheresis)

• Number of Transplants in Which Participants Achieved Polymorphonuclear Leukocyte (PMN) Engraftment by Day 12 But No Later Than Day 21 Post Peripheral Blood Stem Cell (PBSC) Transplant

  2 months

• Increase in Peripheral Blood (PB) CD34+ Cells From Steady-state Hematopoiesis to Pre-leukapheresis in G-CSF+Plerixafor Treated Participants Compared to Historical Controls Treated With G-CSF Alone or Chemotherapy and G-CSF

  up to day 8

Other Outcomes (3)

• Median Cumulative Number of CD34+ Cells Collected During Apheresis

  Days 5-8

• Number of Transplants in Which Participants Achieved Platelet (PLT) Engraftment by Day 12 But No Later Than Day 21 Post Peripheral Blood Stem Cell (PBSC) Transplant

  2 months

• Number of Participants With Durable Engraftment 12 Months After Transplantation

  Approximately 13 months (12 months post-transplant )

Study Arms (2)

Non-Hodgkin's Lymphoma (NHL)

EXPERIMENTAL

Participants with NHL were mobilized with granulocyte colony-stimulating factor (G-CSF) 10 µg/kg/day for 4 days. Plerixafor 240 µg/kg was given the evening of day 4 and G-CSF given the next morning followed by apheresis. Evening doses of plerixafor and morning doses of G-CSF followed by apheresis continued for up to a maximum of 5 aphereses or until ≥ 5\*10\^6 CD34+ cells/kg were collected.

Drug: G-CSF Plus Plerixafor

Multiple Myeloma (MM)

EXPERIMENTAL

Participants with MM were mobilized with granulocyte colony-stimulating factor (G-CSF) 10 µg/kg/day for 4 days. Plerixafor 240 µg/kg was given the evening of day 4 and G-CSF given the next morning followed by apheresis. Evening doses of plerixafor and morning doses of G-CSF followed by apheresis continued for up to a maximum of 5 aphereses or until ≥ 5\*10\^6 CD34+ cells/kg were collected.

Drug: G-CSF Plus Plerixafor

Interventions

G-CSF Plus Plerixafor DRUG

Participants underwent mobilization with 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 5 aphereses or until ≥ 5\*10\^6 CD34+ cells/kg were collected.

Also known as: Mozobil, AMD3100

Multiple Myeloma (MM); Non-Hodgkin's Lymphoma (NHL)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of non-Hodgkin's lymphoma (NHL) or multiple myoloma (MM) eligible for autologous transplantation
• No more than 3 prior regimens of chemotherapy
• More than 4 weeks since last cycle of chemotherapy. Patient recovered from all acute toxic effects of prior chemotherapy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• White blood cell (WBC) count \>3.0\*10\^9/L
• Absolute polymorphonuclear cells (PMN) count \>1.5\*10\^9/L
• Platelet (PLT) count \>100\*10\^9/L
• Serum creatinine \<=2.2 mg/dL
• Serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) and total bilirubin \<2 x upper limit of normal (ULN)
• Left ventricle ejection fraction \>45% by normal echocardiogram or multiple-gated acquisition (MUGA) scan
• Negative for human immunodeficiency virus (HIV)
• Women of child bearing potential who agreed to use an approved form of contraception.

You may not qualify if:

• Patients who have failed previous collections
• Brain metastases or carcinomatous meningitis
• History of ventricular arrhythmias
• History of paresthesias
• A co-morbid condition which, in the view of the investigator, renders the patient at high risk for treatment complications
• A residual acute medical condition resulting from prior chemotherapy
• Acute infection
• Fever (temp \>38°C/100.4°F)
• Patients whose actual body weight exceeds 150% of their ideal body weight
• Patients who previously received experimental therapy within 4 weeks of enrolling in this study or who are currently enrolled in another experimental study during the mobilization period
• Positive pregnancy test in female patients
• Lactating females
• Patients of child-bearing potential unwilling to implement adequate birth control.
• Patients who have deterioration of their clinical status or laboratory parameters between the time of enrolment and transplant (such that they no longer meet entry criteria) may be removed from study at the discretion of the treating physician, principal investigator, or sponsor.

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead
• AnorMED: collaborator

Study Sites (3)

University of Cologne

Cologne, Germany

Location

Carl Gustav Carus University Hospital

Dresden, Germany

Location

University of Heidelberg

Heidelberg, Germany

Location

Related Publications (3)

• Fruehauf S, Seeger T, Maier P, Li L, Weinhardt S, Laufs S, Wagner W, Eckstein V, Bridger G, Calandra G, Wenz F, Zeller WJ, Goldschmidt H, Ho AD. The CXCR4 antagonist AMD3100 releases a subset of G-CSF-primed peripheral blood progenitor cells with specific gene expression characteristics. Exp Hematol. 2006 Aug;34(8):1052-9. doi: 10.1016/j.exphem.2006.06.003.

  PMID: 16863911 BACKGROUND

• Fruehauf S, Ehninger G, Hubel K, Topaly J, Goldschmidt H, Ho AD, Muller S, Moos M, Badel K, Calandra G. Mobilization of peripheral blood stem cells for autologous transplant in non-Hodgkin's lymphoma and multiple myeloma patients by plerixafor and G-CSF and detection of tumor cell mobilization by PCR in multiple myeloma patients. Bone Marrow Transplant. 2010 Feb;45(2):269-75. doi: 10.1038/bmt.2009.142. Epub 2009 Jul 13.

  PMID: 19597422 RESULT

• Fruehauf S, Veldwijk MR, Seeger T, Schubert M, Laufs S, Topaly J, Wuchter P, Dillmann F, Eckstein V, Wenz F, Goldschmidt H, Ho AD, Calandra G. A combination of granulocyte-colony-stimulating factor (G-CSF) and plerixafor mobilizes more primitive peripheral blood progenitor cells than G-CSF alone: results of a European phase II study. Cytotherapy. 2009;11(8):992-1001. doi: 10.3109/14653240903121245.

  PMID: 19929463 RESULT

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Multiple Myeloma

Interventions

Granulocyte Colony-Stimulating Factor; plerixafor

Condition Hierarchy (Ancestors)

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

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: Genzyme Medical Information
• Organization: Genzyme Corporation

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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: May 4, 2006
• First Posted: May 8, 2006
• Study Start: September 1, 2004
• Primary Completion: February 1, 2007
• Study Completion: February 1, 2007
• Last Updated: March 13, 2014
• Results First Posted: November 25, 2010

Record last verified: 2014-02

Locations

DE (3)