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

NCT00733824 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 08-0897 / 201105349
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

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.

Conditions

Lymphoma, Non-Hodgkin; Hodgkin Disease

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• 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

Study Arms (5)

Cohort 1

EXPERIMENTAL

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; Drug: G-CSF; Procedure: Apheresis

Cohort 2

EXPERIMENTAL

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; Drug: G-CSF; Procedure: Apheresis

Cohort 3

EXPERIMENTAL

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; Drug: G-CSF; Procedure: Apheresis

Cohort 4

EXPERIMENTAL

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; Drug: G-CSF; Procedure: Apheresis

Phase II

EXPERIMENTAL

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; Drug: G-CSF; Procedure: Apheresis

Interventions

AMD3100 DRUG

Also known as: Plerixafor

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Phase II

G-CSF DRUG

Also known as: Neupogen, Filgrastim

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Phase II

Apheresis PROCEDURE

Also known as: Leukopheresis

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Phase II

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 75 years
• Diagnosis of HL or NHL eligible for autologous transplantation
• 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:

You may not qualify if:

• 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

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (4)

• 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.

  PMID: 15020611 BACKGROUND

• 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.

  PMID: 15890685 BACKGROUND

• 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-.

  BACKGROUND

• 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.

  PMID: 18940680 BACKGROUND

Related Links

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

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Hodgkin Disease; Lymphoma

Interventions

plerixafor; Granulocyte Colony-Stimulating Factor; Filgrastim; Blood Component Removal; Leukapheresis

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Therapeutics; Cytapheresis; Biological Therapy; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques

Results Point of Contact

• Title: Amanda F. Cashen, M.D.
• Organization: Washington University School of Medicine

acashen@wustl.edu

314-454-8304

Study Officials

• Amanda F. Cashen, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2008
• First Posted: August 13, 2008
• Study Start: November 1, 2008
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2013
• Last Updated: March 9, 2017
• Results First Posted: October 28, 2016

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)