Intravenous AMD3100 for Collection of Autologous Peripheral Blood Stem Cells in Patients With Lymphoma

Lymphoma, Non-Hodgkin Clinical Trial

Official title:

A Phase I/II Study of Intravenous AMD3100 Added to a Mobilization Regimen of G-CSF to Increase the Number of Autologous Peripheral Blood Stem Cells Collected From Patients With Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00733824
• Other study ID #: 08-0897 / 201105349
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: August 11, 2008
• Last updated: February 13, 2014
• Start date: November 2008
• Est. completion date: September 2013

Study information

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

Clinical Trial Summary

This study will evaluate the safety and efficacy of intravenous AMD3100 added to a standard G-CSF mobilization regimen of patients undergoing autologous stem cell transplantation for lymphoma.

We hypothesize that after stem cell mobilization with G-CSF plus IV AMD3100, a significantly higher proportion of lymphoma patients will collect ≥ 2 x 10E6 CD34+ cells/kg.

Description:

Autologous stem cell transplantation (ASCT) is indicated for patients with non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL) who have primary progressive disease or who relapse after a chemotherapy-induced complete remission. For these patients, as for other patients undergoing autologous transplantation, the number of CD34+ cells collected is a reliable predictor of neutrophil and platelet (PLT) engraftment after transplantation.

AMD3100 (plerixafor) is a promising new mobilizing agent that has demonstrated efficacy in patients with NHL, HL, and multiple myeloma (MM). Although efficacious, the subcutaneous dosing of AMD3100 requires that patients receive the drug in the evening prior to apheresis, which can present logistical problems. Intravenous dosing of AMD3100 may result in a faster rise in peripheral CD34+ cell count, so that the drug can be administered the same day as apheresis. Intravenous dosing may also increase the peak CD34+ cell count, improving the number of CD34+ cells collected via apheresis.

This Phase I/II study will evaluate the safety and efficacy of intravenous AMD3100 added to the standard G-CSF mobilization regimen of patients undergoing autologous stem cell transplantation for Hodgkin and non-Hodgkin lymphomas.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: September 2013
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Age 18 to 75 years

• Diagnosis of HL or NHL eligible for autologous transplantation

• 30 days since last cycle of chemotherapy

• ECOG performance status of 0 or 1

• The patient has recovered from all acute toxic effects of prior chemotherapy

• WBC >3.0 X 109/l

• Absolute PMN count >1.5 X 109/l

• PLT count >100 X 109/l

• Serum creatinine = 2.2 mg/dl

• AST (SGOT), ALT (SGPT) and total bilirubin < 2X upper limit of normal (ULN)

• Left ventricle ejection fraction > 45% (by ECHO or MUGA scan)

• FEV1 > 60% of predicted or DLCO > 45% of predicted

• Negative for HIV on standard transplant workup

• Signed informed consent

• Are surgically or biologically sterile or willing to practice acceptable birth control, as follows:

• Females of child bearing potential must agree to abstain from sexual activity or to use a medically approved contraceptive measure/regimen during and for 3 months after the treatment period. Women of child bearing potential must have a negative serum or urine pregnancy test at the time of enrollment. Acceptable methods of birth control include oral contraceptive, intrauterine device (IUD), transdermal/implanted or injected contraceptives and abstinence.

• Males must agree to abstain from sexual activity or agree to utilize a medically approved contraception method during and for 3 months after the treatment period

Exclusion Criteria:

• A co-morbid condition which, in the view of the investigator, renders the patient at high risk for treatment complications

• Patients who have failed previous collections

• A residual acute medical condition resulting from prior chemotherapy

• Acute infection

• Fever (temp >38C/100.4F) on the day of start of treatment

• Positive pregnancy test in female patients

• Lactating females

• Patients of child bearing potential unwilling to implement adequate birth control

• Patients whose actual body weight exceeds 150% of their ideal body weight

• History of ventricular arrhythmias

• Patients who previously received experimental therapy within 4 weeks of enrolling in this study or who are currently enrolled in another experimental study during the mobilization phase

• Patients who have deterioration of their clinical status or laboratory parameters between the time of enrollment and transplantation 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
• Lymphoma, Non-Hodgkin

Intervention

Drug:
• AMD3100

• G-CSF

Procedure:
• Apheresis

Locations

Country	Name	City	State
United States	Washington University School of Medicine	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

References & Publications (4)

Cashen A, Lopez S, Gao F, Calandra G, MacFarland R, Badel K, DiPersio J. A phase II study of plerixafor (AMD3100) plus G-CSF for autologous hematopoietic progenitor cell mobilization in patients with Hodgkin lymphoma. Biol Blood Marrow Transplant. 2008 Nov;14(11):1253-61. doi: 10.1016/j.bbmt.2008.08.011. — View Citation

Devine SM, Flomenberg N, Vesole DH, Liesveld J, Weisdorf D, Badel K, Calandra G, DiPersio JF. Rapid mobilization of CD34+ cells following administration of the CXCR4 antagonist AMD3100 to patients with multiple myeloma and non-Hodgkin's lymphoma. J Clin Oncol. 2004 Mar 15;22(6):1095-102. — View Citation

DiPersio JF, Micallef I, Stiff PJ, et al. A Phase III, Multicenter, Randomized, Double-Blind, Placebo Controlled, Comparative Trial of AMD3100 (Plerixafor)+G-CSF vs. Placebo+G-CSF in Non-Hodgkin's Lymphoma (NHL) Patients for Autologous Hematopoietic Stem Cell (aHSC) Transplantation. ASH Annual Meeting Abstracts. November 16, 2007 2007;110(11):601-.

Flomenberg N, Devine SM, Dipersio JF, Liesveld JL, McCarty JM, Rowley SD, Vesole DH, Badel K, Calandra G. The use of AMD3100 plus G-CSF for autologous hematopoietic progenitor cell mobilization is superior to G-CSF alone. Blood. 2005 Sep 1;106(5):1867-74. Epub 2005 May 12. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the maximum tolerated dose of IV AMD3100 + G-CSF in mobilization of peripheral blood stem cell in patients with lymphoma		7 days from first dose of IV AMD3100	Yes
Secondary	To determine the kinetics of stem cell mobilization using IV AMD3100 in this patient population		1 year	No
Secondary	To determine whether the pharmacodynamic response to a dose of SC AMD3100, as measured by circulating CD34+ cell count, correlates with stem cell mobilization with G-CSF and with G-CSF + IV AMD3100.		1 year	No
Secondary	To determine the toxicity and efficacy of the combination IV AMD3100 and G-CSF to mobilize = 2 x 106 CD34+ cells/kg from patients with lymphoma (Hodgkin and non-Hodgkin) who are undergoing autologous stem cell transplantation		Toxicity=30 days post transplant, Efficacy = 1 year	Yes

External Links

•   Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine