AMD3100-2113: The Effect of Rituximab on Mobilization With AMD3100 Plus G-CSF in Patients With Relapsed or Refractory NHL or HD

This study is currently recruiting patients.

Sponsored By:	Genzyme AnorMED Corporation, a wholly owned subsidiary of Genzyme Corporation.
Information Provided By:	Genzyme
ClinicalTrials.gov Identifier:	NCT00444912

Purpose

Patients with NHL or HD will be assigned to one of 2 arms based on the immunophenotype of their lymphoma.

(A)Patients with CD20(-) lymphoma will undergo mobilization with G-CSF and AMD3100.
(B) Patients with CD20(+) lymphomas will undergo mobilization with Rituxan®, G-CSF, and AMD3100. They will receive a weekly dose of Rituxan® beginning 1 week prior to, and continuing until 2 weeks after, the first dose of G-CSF.

Patients in both groups will receive G-CSF twice daily for 4 days. In the evening on Day 4, a dose of AMD3100 will be administered. Apheresis will be initiated the next morning, Patients will continue to receive G-CSF twice daily and to receive the evening dose of AMD3100 followed by apheresis the next morning for up to a total of 4 aphereses or until ≧ 5 x 10e6 CD34+ cells/kg are collected.

Patients who are transplanted will be monitored for the time to PMN, PLT, and lymphocyte engraftment. Follow-up assessments will be done at 100 days, and 6 and 12 months post-transplantation.

Condition	Intervention	Phase
Non-Hodgkin's Lymphoma Hodgkin's Disease	Drug: AMD3100	Phase II

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Safety/Efficacy Study

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

Further Study Details:

Primary Outcomes: To evaluate the safety of AMD3100 when used in combination with Rituxan® and G-CSF in patients with relapsed or refractory HD or NHL.

Secondary Outcomes:To compare the 2 treatment arms with respect to the number of CD34+ cells collected; the increase in circulating CD34+ cells after AMD3100 administration; the number of apheresis days required to reach the target of ≥5 x 10e6 CD34+ cells/kg; the number of apheresis days required to reach a minimum of 3 x 10e6 CD34+ cells/kg; PMN, PLT, and lymphocyte engraftment times; the kinetics of lymphocyte, T-cell, B-cell, NK cell, and dendritic cell recovery post-transplant; the content of B-cells in the grafts collected; durability of engraftment after autologous transplantation

Expected Total Enrollment: 30

Study start: March 2006

This is a single-center, observational, 2-arm, non-randomized, open-label study to evaluate the safety of AMD3100 when used in combination with rituximab (Rituxan®) and granulocyte colony-stimulating factor (G-CSF) in patients with relapsed or refractory Hodgkin’s disease (HD) or non-Hodgkin’s lymphoma (NHL).

Patients will be assigned to one of 2 arms based on the immunophenotype of their lymphoma.
(A)Patients with CD20(-) lymphoma will undergo mobilization with G-CSF and AMD3100.
(B) Patients with CD20(+) lymphomas will undergo mobilization with Rituxan®, G-CSF, and AMD3100. They will receive a weekly dose of 375 mg/m2 Rituxan® by intravenous (iv) infusion beginning 1 week prior to, and continuing until 2 weeks after, the first dose of G-CSF.

Patients 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 AMD3100 (240 µg/kg) will be administered. Apheresis will be initiated the next morning, approximately 10 to 11 hours after AMD3100 is given. Patients will continue to receive G-CSF twice daily and to receive the evening dose of AMD3100 followed by apheresis the next morning for up to a total of 4 aphereses or until ≧ 5 x 10e6 CD34+ cells/kg are collected.

Patients 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. Patients 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.

Eligibility

Ages Eligible for Study: 18 Years - 70 Years

Genders Eligible for Study: Both

Criteria

Inclusion Criteria:

Histological diagnosis of diffuse large cell lymphoma, B-cell, T-cell or anaplastic histologies; peripheral T-cell lymphoma; small non-cleaved Birkitt-like lymphoma; or Hodgkin’s disease. NOTE: Patients 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 (e.g., CHOP, ABVD) 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.

ECOG performance status of 0, 1, or 2.

Absolute granulocytes count ≧1.0 x 10e9/l.

PLT count ≧75 x 10e9/l.

AST or ALT ≦2.5 x upper limit of normal (ULN) or ≦5 x 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

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 Rituxan®.

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 x ULN.

Bilirubin >1.5 x 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.

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.

Location Information

Georgia
Winship Cancer Institute, Atlanta, Georgia, 30322, United States; Recruiting

More Information

Study ID Numbers: AMD3100-2113
ClinicalTrials.gov Identifier: NCT00444912
Health Authority: United States: Food and Drug Administration