Clinical trial NCT00733824: Intravenous AMD3100 for Collection of Autologous Peripheral Blood Stem Cells in Patients With Lymphoma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Lymphoma, Non-Hodgkin
Hodgkin Disease
Keywords: Plerixafor
Lymphoma
Hematopoietic Stem Cell Mobilization
Transplantation, Autologous
Receptors, CXCR4
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2008-08-13
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

The investigators 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of IV AMD3100 + G-CSF in Mobilization of Peripheral Blood Stem Cell in Patients With Lymphoma (Phase I Only)
timeFrame: 7 days from first dose of IV AMD3100
measure: Number of Participants Who Experienced Dose Limiting Toxicities in Phase I Portion of Study
timeFrame: 7 days from first dose of IV AMD3100
Secondary outcomes:
measure: Kinetics of Stem Cell Mobilization Using IV AMD3100 as Measured by Median Fold Change in the Number of CD34+ Cells After AMD3100 IV Administration
timeFrame: From baseline to Day 1
measure: Pharmacodynamic Response to a Dose of SC AMD3100 as Measured by Mean Percentage of the Circulating CD34+ Count With the 34+RA-123+/- Phenotype
timeFrame: 1 year
measure: Toxicity of the Combination IV AMD3100 and G-CSF to Mobilize ≥ 2 x 106 CD34+ Cells/kg as Measured by Number of Participants Who Experience Grade 3 or Higher Adverse Event Broken Down by Adverse Event
timeFrame: 30 days post transplant
Other outcomes:
Locations:
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Amanda F. Cashen, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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. doi: 10.1200/JCO.2004.07.131.
citation: 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. doi: 10.1182/blood-2005-02-0468. Epub 2005 May 12.
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-.
citation: 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.