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

Primary Purpose

Lymphoma, Non-Hodgkin, Hodgkin Disease

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

AMD3100

G-CSF

Apheresis

About this trial

This is an interventional treatment trial for Lymphoma, Non-Hodgkin focused on measuring Plerixafor, Lymphoma, Hematopoietic Stem Cell Mobilization, Transplantation, Autologous, Receptors, CXCR4

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Washington University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Arm Label

Cohort 1

Cohort 2

Cohort 3

Cohort 4

Phase II

Arm Description

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)

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)

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)

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)

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)

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

Kinetics of Stem Cell Mobilization Using IV AMD3100 as Measured by Median Fold Change in the Number of CD34+ Cells After AMD3100 IV Administration

Pharmacodynamic Response to a Dose of SC AMD3100 as Measured by Mean Percentage of the Circulating CD34+ Count With the 34+RA-123+/- Phenotype

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

Full Information

NCT ID

NCT00733824

First Posted

August 11, 2008

Last Updated

January 26, 2017

Sponsor

Washington University School of Medicine

1. Study Identification

Unique Protocol Identification Number

NCT00733824

Brief Title

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

2. Study Status

Record Verification Date

January 2017

Overall Recruitment Status

Completed

Study Start Date

November 2008 (undefined)

Primary Completion Date

September 2012 (Actual)

Study Completion Date

September 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Washington University School of Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lymphoma, Non-Hodgkin, Hodgkin Disease

Keywords

Plerixafor, Lymphoma, Hematopoietic Stem Cell Mobilization, Transplantation, Autologous, Receptors, CXCR4

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

61 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cohort 1

Arm Type

Experimental

Arm Description

Arm Title

Cohort 2

Arm Type

Experimental

Arm Description

Arm Title

Cohort 3

Arm Type

Experimental

Arm Description

Arm Title

Cohort 4

Arm Type

Experimental

Arm Description

Arm Title

Phase II

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

AMD3100

Other Intervention Name(s)

Plerixafor

Intervention Type

Drug

Intervention Name(s)

G-CSF

Other Intervention Name(s)

Neupogen, Filgrastim

Intervention Type

Procedure

Intervention Name(s)

Apheresis

Other Intervention Name(s)

Leukopheresis

Primary Outcome Measure Information:

Title

Maximum Tolerated Dose (MTD) of IV AMD3100 + G-CSF in Mobilization of Peripheral Blood Stem Cell in Patients With Lymphoma (Phase I Only)

Description

Time Frame

7 days from first dose of IV AMD3100

Title

Number of Participants Who Experienced Dose Limiting Toxicities in Phase I Portion of Study

Description

Dose limiting toxicity: selected grade III or higher (hematologic, cardiac, pulmonary, hepatobiliary/pancreatic, renal, or CNS) not attributable to any other cause.

Time Frame

7 days from first dose of IV AMD3100

Secondary Outcome Measure Information:

Title

Kinetics of Stem Cell Mobilization Using IV AMD3100 as Measured by Median Fold Change in the Number of CD34+ Cells After AMD3100 IV Administration

Time Frame

From baseline to Day 1

Title

Pharmacodynamic Response to a Dose of SC AMD3100 as Measured by Mean Percentage of the Circulating CD34+ Count With the 34+RA-123+/- Phenotype

Time Frame

1 year

Title

Time Frame

30 days post transplant

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Amanda F. Cashen, M.D.

Organizational Affiliation

Washington University School of Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Washington University School of Medicine

City

St. Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

15020611

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.

Results Reference

background

PubMed Identifier

15890685

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.

Results Reference

background

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-.

Results Reference

background

PubMed Identifier

18940680

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.

Results Reference

background

Links:

URL

http://www.siteman.wustl.edu

Description

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

Learn more about this trial

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

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