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

The Washington University

Status and phase: Completed; Phase 2; Phase 1

Conditions: Hodgkin Disease; Lymphoma, Non-Hodgkin

Treatments: Procedure: Apheresis; Drug: G-CSF; Drug: AMD3100

Study type: Interventional

Funder types: Other

Identifiers

NCT00733824

08-0897 / 201105349

Details and patient eligibility

About

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.

Full 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.

Enrollment: 61 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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61 participants in 5 patient groups

Cohort 1

Experimental group

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)

Treatment:

Drug: AMD3100

Drug: G-CSF

Procedure: Apheresis

Cohort 2

Experimental group

Description:

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)

Treatment:

Drug: AMD3100

Drug: G-CSF

Procedure: Apheresis

Cohort 3

Experimental group

Description:

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)

Treatment:

Drug: AMD3100

Drug: G-CSF

Procedure: Apheresis

Cohort 4

Experimental group

Description:

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)

Treatment:

Drug: AMD3100

Drug: G-CSF

Procedure: Apheresis

Phase II

Experimental group

Description:

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)

Treatment:

Drug: AMD3100

Drug: G-CSF

Procedure: Apheresis