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)

Phase 2

Completed

Conditions: Non-Hodgkin Lymphoma
Hodgkin Disease

Interventions: Drug: G-CSF plus plerixafor
Biological: rituximab

Registration Number: NCT00444912

Lead Sponsor: Genzyme, a Sanofi Company

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.

Detailed Description: This is a single-center, 2-arm, non-randomized, open-label study to evaluate the safety of plerixafor when used in combination with rituximab (Rituxan®) and granulocyte colony-stimulating factor (G-CSF) in patients with relapsed or refractory Hodgkin disease (HD) or non-Hodgkin lymphoma (NHL).

Participants will be assigned to one of 2 arms based on the immunophenotype of their lymphoma.

(A)Participants with CD20(-) lymphoma will undergo mobilization with 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 375 mg/m2 rituximab by intravenous (iv) infusion beginning 1 week prior to, and continuing until 2 weeks after, the first dose of G-CSF.

Participants in both groups will receive 7.5 µg/kg G-CSF twice daily (morning and evening) for 4 days. In the evening (approximately 10:00 pm) on Day 4, a dose of plerixafor (240 µg/kg) will be administered. Apheresis will be initiated the next morning, approximately 10 to 11 hours after plerixafor is given. 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 with an adequate number of autologous peripheral blood stem cells (PBSCs) collected by apheresis will be admitted to the study center for the administration of high-dose chemotherapy and autologous transplantation. After transplantation, the times to PMN, PLT, and lymphocyte engraftment will be measured. Participants will remain hospitalized until they achieve an absolute granulocyte count of \>500/µl in the peripheral blood. Graft durability will be assessed at 100 days, and 6 and 12 months post-transplantation.

This study was previously posted by AnorMED, Inc. In November 2006, AnorMED, Inc. was acquired by Genzyme Corporation. Genzyme Corporation is the sponsor of the trial.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 30

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
G-CSF plus plerixafor	G-CSF plus plerixafor	Participants with CD20- lymphoma
G-CSF plus plerixafor and rituximab	G-CSF plus plerixafor	Participants with CD20+ lymphoma
G-CSF plus plerixafor and rituximab	rituximab	Participants with CD20+ lymphoma

Primary Outcome Measures

Name	Time	Method
Summary of Adverse Events (AEs)	Day 1 and up to Day 59 (maximum time before start of chemotherapy)	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.

Secondary Outcome Measures

Name	Time	Method
Median Cumulative Number of CD34+ Cells Collected During Apheresis	Days 5-8	Median total number of CD34+ cells collected during apheresis.
Median Fold Increase in the Number of CD34+ Cells After Plerixafor Administration	Days 4-5	Fold Increase = (Pre-Apheresis CD34+ cells/Pre-Plerixafor CD34+ cells).
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 in each treatment arm to collect a minimum of 3\*10\^6 CD34+ cells/kg.
Median Number of Apheresis Days Required to Reach the Target of 5*10^6 CD34+ Cells/kg	Days 5-8	Median number of apheresis days in each treatment arm to reach the target of 5\*10\^6 CD34+ cells/kg.
Median Number of Days to Polymorphonuclear Leukocyte (PMN) Engraftment	Days post transplantation (approximately Day 40)	Median number of days from transplantation to PMN engraftment which was defined as PMN counts ≥0.5\10\^9/L for 3 consecutive days or ≥1.0\10\^9/L for 1 day. Time to engraftment corresponded to the first day that the criteria were met.
Median Number of Days to Platelet (PLT) Engraftment	Days post transplantation (approximately Day 40)	Median number of days from transplantation to PLT engraftment which was defined as platelet counts ≥20\10\^9/L without transfusion for the preceding 7 days or platelet counts ≥50\10\^9/L for one day. Time to engraftment corresponded to the first day that the criteria were met.
Median Number of Days to Lymphocyte Engraftment	Days post transplantation (approximately Day 40)	Median number of days from transplantation to lymphocyte engraftment which was defined as lymphocyte counts ≥5\*10\^8/L. Time to engraftment corresponded to the first day that criteria were met.
Median Level of CD19+CD2-CD14- B-cells Six Months Post-Transplant	Approximately 7 months (6 months post-transplant)
Median Level of CD19+CD2-CD14- B-cells Twelve Months Post-Transplant	13 months (12 months post-transplant)
The Percentage of CD19+CD3-CD14- B-cells of the Total Cells on the First Apheresis Day	Day 5
Number of Participants With Durable Engraftment 12 Months After Transplantation	Approximately 13 months (12 months post-transplant )	The number of participants maintaining a durable graft 12 months after autologous transplantation. A durable graft is defined as the maintenance of normal blood counts.