Clinical trial NCT00444912: 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)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-Hodgkin Lymphoma
Hodgkin Disease
Keywords: AMD3100
stem cell mobilization
autologous transplant
Non-Hodgkin Lymphoma
Hodgkin Disease
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2007-03-08
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Summary of Adverse Events (AEs)
timeFrame: Day 1 and up to Day 59 (maximum time before start of chemotherapy)
Secondary outcomes:
measure: Median Cumulative Number of CD34+ Cells Collected During Apheresis
timeFrame: Days 5-8
measure: Median Fold Increase in the Number of CD34+ Cells After Plerixafor Administration
timeFrame: Days 4-5
measure: Median Number of Apheresis Days Required to Reach a Minimum of 3*10^6 CD34+ Cells/kg
timeFrame: Days 5-8
measure: Median Number of Apheresis Days Required to Reach the Target of 5*10^6 CD34+ Cells/kg
timeFrame: Days 5-8
measure: Median Number of Days to Polymorphonuclear Leukocyte (PMN) Engraftment
timeFrame: Days post transplantation (approximately Day 40)
measure: Median Number of Days to Platelet (PLT) Engraftment
timeFrame: Days post transplantation (approximately Day 40)
measure: Median Number of Days to Lymphocyte Engraftment
timeFrame: Days post transplantation (approximately Day 40)
measure: Median Level of CD19+CD2-CD14- B-cells Six Months Post-Transplant
timeFrame: Approximately 7 months (6 months post-transplant)
measure: Median Level of CD19+CD2-CD14- B-cells Twelve Months Post-Transplant
timeFrame: 13 months (12 months post-transplant)
measure: The Percentage of CD19+CD3-CD14- B-cells of the Total Cells on the First Apheresis Day
timeFrame: Day 5
measure: Number of Participants With Durable Engraftment 12 Months After Transplantation
timeFrame: Approximately 13 months (12 months post-transplant )
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Winship Cancer Institute
state: Georgia
Study officials:
affiliation: Genzyme, a Sanofi Company
name: Medical Monitor
role: STUDY_DIRECTOR
References: