The Effect of Rituximab on Mobilization With AMD3100 (Plerixafor) Plus G-CSF in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma (NHL) or Hodgkin Disease (HD)

NCT00444912 | Completed Phase 2 Results DMC

• 1 other identifier: AMD31002113
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Participants with non-Hodgkin lymphoma (NHL) or Hodgkin disease (HD) will be assigned to one of 2 arms based on the immunophenotype of their lymphoma. (A)Participants with CD20(-) lymphoma will undergo mobilization with granulocyte colony-stimulating factor (G-CSF) and plerixafor. (B) Participants with CD20(+) lymphomas will undergo mobilization with rituximab, G-CSF, and plerixafor. They will receive a weekly dose of rituximab beginning 1 week prior to, and continuing until 2 weeks after, the first dose of G-CSF. Participants in both groups will receive G-CSF twice daily for 4 days. In the evening on Day 4, a dose of plerixafor will be administered. Apheresis will be initiated the next morning. Participants will continue to receive G-CSF twice daily and to receive the evening dose of plerixafor followed by apheresis the next morning for up to a total of 4 aphereses or until ≥5\*10\^6 CD34+ cells/kg are collected. Participants who are transplanted will be monitored for the time to polymorphonuclear leukocytes (PMN), platelets (PLT), and lymphocyte engraftment. Follow-up assessments will be done at 100 days, and 6 and 12 months post-transplantation.

Conditions

Non-Hodgkin Lymphoma; Hodgkin Disease

Keywords

AMD3100; stem cell mobilization; autologous transplant; Non-Hodgkin Lymphoma; Hodgkin Disease

Outcome Measures

Primary Outcomes (1)

• Summary of Adverse Events (AEs)

  Number of participants with adverse events (AEs) collected from Day 1 (start of G-CSF mobilization in participants with CD20- lymphoma or start of rituximab in participants with CD20+ lymphoma) 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 seriousness and relatedness to study treatment.

  Day 1 and up to Day 59 (maximum time before start of chemotherapy)

Secondary Outcomes (11)

• Median Cumulative Number of CD34+ Cells Collected During Apheresis

  Days 5-8

• Median Fold Increase in the Number of CD34+ Cells After Plerixafor Administration

  Days 4-5

• Median Number of Apheresis Days Required to Reach a Minimum of 3*10^6 CD34+ Cells/kg

  Days 5-8

• Median Number of Apheresis Days Required to Reach the Target of 5*10^6 CD34+ Cells/kg

  Days 5-8

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

  Days post transplantation (approximately Day 40)

Study Arms (2)

G-CSF plus plerixafor

EXPERIMENTAL

Participants with CD20- lymphoma

Drug: G-CSF plus plerixafor

G-CSF plus plerixafor and rituximab

EXPERIMENTAL

Participants with CD20+ lymphoma

Drug: G-CSF plus plerixafor; Biological: rituximab

Interventions

G-CSF plus plerixafor DRUG

Participants underwent mobilization with G-CSF (7.5 µg/kg twice daily) for 4 days, administered by subcutaneous (sc) injection. 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 (7.5 µg/kg) and underwent apheresis approximately 10 to 11 hours after the dose of plerixafor. Participants were to continue to receive G-CSF twice daily and to receive the evening dose of plerixafor followed by apheresis the following morning for a maximum of 4 aphereses or until ≥ 5\*10\^6 CD34+ cells/kg were collected.

Also known as: AMD3100, Mozobil

G-CSF plus plerixafor

rituximab BIOLOGICAL

Participants were given a weekly dose of rituximab 375mg/m2 by intravenous infusion for 1 week prior to and continuing until 2 weeks after the first dose of G-CSF.

Also known as: Rituxan, MabThera

G-CSF plus plerixafor and rituximab

Eligibility Criteria

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

You may qualify if:

• Histological diagnosis of diffuse large cell lymphoma, B-cell, T-cell or anaplastic histologies; peripheral T-cell lymphoma; small non-cleaved Burkitt-like lymphoma; or Hodgkin disease. NOTE: Participants diagnosed at a facility outside of Emory University will have their diagnosis confirmed by Emory University pathologists prior to being enrolled in this study.
• Eligible for autologous transplantation.
• History of relapse of lymphoma following initial treatment with an anthracycline-containing regimen or disease that is refractory or progresses during initial therapy with an anthracycline-containing regimen.
• Immunophenotyping of the lymphoma at the time of diagnosis or relapse using flow cytometry or immunohistochemistry.
• Presence of clinically- and/or radiologically-documented, measurable, and/or evaluable disease at the time of relapse.
• Received 2 cycles of salvage chemotherapy.
• Complete response (i.e., normal physical examination, lymph nodes, lymph node masses, and bone marrow) or a partial response (i.e., decrease of ≧50% in the size of lymph nodes or lymph node masses or decrease in size of liver/spleen on physical exam) to at least one cycle of a salvage chemotherapy regimen.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• Absolute granulocytes count ≧1.0\*10\^9/l.
• Platelet count ≧75\*10\^9/l.
• Aspartate aminotransferase (AST) or alanine transaminase (ALT) ≦2.5 times the upper limit of normal (ULN) or ≦5 times the ULN if liver involvement with lymphoma.
• Life expectancy of at least 3 months.
• \>4 weeks since last cycle of chemotherapy.
• Patient has recovered from all acute toxic effects of prior chemotherapy.
• Signed informed consent.

You may not qualify if:

• A second active malignancy (other than basal cell carcinoma of the skin).
• Uncontrolled central nervous system involvement by lymphoma.
• Positive/history of retroviral infection (HIV, HTLV-1).
• Active infection requiring antibiotics during planned lymphoma-related therapy.
• Previous treatment with high-dose chemotherapy or cytokine mobilization and hematopoietic progenitor cell transplantation.
• Continued evidence by morphology and flow cytometry of bone marrow involvement after at least one cycle of salvage chemotherapy.
• ≥3 cycles of salvage chemotherapy following documentation of lymphoma relapse or disease progression.
• (In patients with CD20(+) lymphoma) History of severe hypersensitivity reactions to rituximab.
• Positive pregnancy test in female patients.
• Lactating female patients.
• Previously received experimental therapy within 4 weeks of enrolling in this protocol or currently enrolled in another experimental protocol during G-CSF Mobilization Phase.
• Creatinine \>1.5 times the ULN.
• Bilirubin \>1.5 times the ULN.
• Ejection fraction \<45%.
• Diffusion capacity of the lung for carbon monoxide (DLCO) \<50%.

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead

Study Sites (1)

Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Hodgkin Disease

Interventions

Granulocyte Colony-Stimulating Factor; plerixafor; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System 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; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Information
• 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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 7, 2007
• First Posted: March 8, 2007
• Study Start: February 1, 2006
• Primary Completion: June 1, 2009
• Study Completion: June 1, 2009
• Last Updated: March 13, 2014
• Results First Posted: July 29, 2010

Record last verified: 2014-02

Locations

US (1)