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)

Non-Hodgkin Lymphoma Clinical Trial

Official title:

A Pilot Cohort Study of AMD3100 in Combination With G-CSF and Rituximab Compared With AMD3100 in Combination With G-CSF Alone for Mobilization of BPCs in Patients With Relapsed or Refractory NHL or HD Prior to Autologous HPC Transplant

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00444912
• Other study ID #: AMD31002113
• Status: Completed
• Phase: Phase 2
• First received: March 7, 2007
• Last updated: February 10, 2014
• Start date: February 2006
• Est. completion date: June 2009

Study information

• Verified date: February 2014
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: June 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria (abbreviated list):

• 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.

Exclusion Criteria (abbreviated list):

• 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%.

• Patients of childbearing potential unwilling to implement adequate birth control.

• A co-morbid condition that renders the patient at high risk from treatment complications.

• Residual acute medical condition resulting from prior chemotherapy.

• Documented history of ventricular arrhythmias during the last 3 years.

• Fever (temperature >38 °C/100.4 °F).

• Actual body weight exceeds 175% of ideal body weight.

• Participants 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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hodgkin Disease
• Lymphoma, Non-Hodgkin
• Non-Hodgkin Lymphoma

Intervention

Drug:
• G-CSF plus plerixafor
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.
• G-CSF plus plerixafor
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.

Biological:
• rituximab
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.

Locations

Country	Name	City	State
United States	Winship Cancer Institute	Atlanta	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
Genzyme, a Sanofi Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	Yes
Secondary	Median Cumulative Number of CD34+ Cells Collected During Apheresis	Median total number of CD34+ cells collected during apheresis.	Days 5-8	No
Secondary	Median Fold Increase in the Number of CD34+ Cells After Plerixafor Administration	Fold Increase = (Pre-Apheresis CD34+ cells/Pre-Plerixafor CD34+ cells).	Days 4-5	No
Secondary	Median Number of Apheresis Days Required to Reach a Minimum of 3*10^6 CD34+ Cells/kg	Median number of apheresis days in each treatment arm to collect a minimum of 3*10^6 CD34+ cells/kg.	Days 5-8	No
Secondary	Median Number of Apheresis Days Required to Reach the Target of 5*10^6 CD34+ Cells/kg	Median number of apheresis days in each treatment arm to reach the target of 5*10^6 CD34+ cells/kg.	Days 5-8	No
Secondary	Median Number of Days to Polymorphonuclear Leukocyte (PMN) Engraftment	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.	Days post transplantation (approximately Day 40)	No
Secondary	Median Number of Days to Platelet (PLT) Engraftment	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.	Days post transplantation (approximately Day 40)	No
Secondary	Median Number of Days to Lymphocyte Engraftment	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.	Days post transplantation (approximately Day 40)	No
Secondary	Median Level of CD19+CD2-CD14- B-cells Six Months Post-Transplant		Approximately 7 months (6 months post-transplant)	No
Secondary	Median Level of CD19+CD2-CD14- B-cells Twelve Months Post-Transplant		13 months (12 months post-transplant)	No
Secondary	The Percentage of CD19+CD3-CD14- B-cells of the Total Cells on the First Apheresis Day		Day 5	No
Secondary	Number of Participants With Durable Engraftment 12 Months After Transplantation	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.	Approximately 13 months (12 months post-transplant )	No