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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Lymphoma, Non-Hodgkin, Hodgkin Disease

Intervention / Treatment
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* Drug: AMD3100
* Drug: G-CSF
* Procedure: Apheresis


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>240 µg/kg SC AMD3100 Day -5 10 µg/kg SC G-CSF Day -4 thru Day -1 160 µg/kg IV AMD3100 and 10 µg/kg SC G-CSF Day 1 Pheresis (this will be repeated on Day 2 through Day 4 until target of ≥5X106 CD34+ cell/kg is reached) | Drug: AMD3100<br> <br> * Other names: Plerixafor;Drug: G-CSF<br> <br> * Other names: Filgrastim;Procedure: Apheresis<br> <br> * Other names: Leukopheresis;|
| Experimental: Cohort 2<br>240 µg/kg SC AMD3100 Day -5 10 µg/kg SC G-CSF Day -4 thru Day -1 240 µg/kg IV AMD3100 and 10 µg/kg SC G-CSF Day 1 Pheresis (this will be repeated on Day 2 through Day 4 until target of ≥5X106 CD34+ cell/kg is reached) | Drug: AMD3100<br> <br> * Other names: Plerixafor;Drug: G-CSF<br> <br> * Other names: Filgrastim;Procedure: Apheresis<br> <br> * Other names: Leukopheresis;|
| Experimental: Cohort 3<br>240 µg/kg SC AMD3100 Day -5 10 µg/kg SC G-CSF Day -4 thru Day -1 320 µg/kg IV AMD3100 and 10 µg/kg SC G-CSF Day 1 Pheresis (this will be repeated on Day 2 through Day 4 until target of ≥5X106 CD34+ cell/kg is reached) | Drug: AMD3100<br> <br> * Other names: Plerixafor;Drug: G-CSF<br> <br> * Other names: Filgrastim;Procedure: Apheresis<br> <br> * Other names: Leukopheresis;|
| Experimental: Cohort 4<br>240 µg/kg SC AMD3100 Day -5 10 µg/kg SC G-CSF Day -4 thru Day -1 400 µg/kg IV AMD3100 and 10 µg/kg SC G-CSF Day 1 Pheresis (this will be repeated on Day 2 through Day 4 until target of ≥5X106 CD34+ cell/kg is reached) | Drug: AMD3100<br> <br> * Other names: Plerixafor;Drug: G-CSF<br> <br> * Other names: Filgrastim;Procedure: Apheresis<br> <br> * Other names: Leukopheresis;|
| Experimental: Phase II<br>240 µg/kg SC AMD3100 Day -5 10 µg/kg SC G-CSF Day -4 thru Day -1 MTD as determined in Phase I IV AMD3100 and 10 µg/kg SC G-CSF Day 1 Pheresis (this will be repeated on Day 2 through Day 4 until target of ≥5X106 CD34+ cell/kg is reached) | Drug: AMD3100<br> <br> * Other names: Plerixafor;Drug: G-CSF<br> <br> * Other names: Filgrastim;Procedure: Apheresis<br> <br> * Other names: Leukopheresis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) of IV AMD3100 + G-CSF in Mobilization of Peripheral Blood Stem Cell in Patients With Lymphoma (Phase I Only) | MTD: the highest dose level of AMD3100 at which ≤ 1 of 6 participants experience a dose limiting toxicity (DLT). The MTD will be the Phase II dose. DLT: selected grade III or higher (hematologic, cardiac, pulmonary, hepatobiliary/pancreatic, renal, or CNS) not attributable to any other cause. | 7 days from first dose of IV AMD3100 | 
| Number of Participants Who Experienced Dose Limiting Toxicities in Phase I Portion of Study | Dose limiting toxicity: selected grade III or higher (hematologic, cardiac, pulmonary, hepatobiliary/pancreatic, renal, or CNS) not attributable to any other cause. | 7 days from first dose of IV AMD3100 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kinetics of Stem Cell Mobilization Using IV AMD3100 as Measured by Median Fold Change in the Number of CD34+ Cells After AMD3100 IV Administration |  | From baseline to Day 1 | 
| Pharmacodynamic Response to a Dose of SC AMD3100 as Measured by Mean Percentage of the Circulating CD34+ Count With the 34+RA-123+/- Phenotype |  | 1 year | 
| 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 |  | 30 days post transplant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Plerixafor, Lymphoma, Hematopoietic Stem Cell Mobilization, Transplantation, Autologous, Receptors, CXCR4