Study of Plerixafor for Rescue of Poor Mobilizers in Autologous Stem Cell Transplant - Full Text View

Purpose

Plerixafor, administered at a dose of 240 ug/kg, potentiates the effect of granulocyte colony-stimulating factor (G-CSF) to increase peripheral blood progenitor cells in both healthy volunteers and cancer patients. Furthermore, in cancer patients, cells collected via apheresis using Plerixafor and G-CSF have been successfully transplanted. In December 2008, Plerixafor received approval from the Food and Drug administration for use in combination with G-CSF to aid in mobilization of progenitor cells for apheresis. The proposed study is not designed to support approval of a new indication or change in the advertising for Plerixafor. The route of administration and dosage level are identical to that which is listed on the package insert. Although Plerixafor is not approved for patients with Hodgkins Lymphoma, there is no known or theoretic increased risk of the use of this drug in this patient population.

The study hypothesis for this study is that patients with a circulating CD34+ count < 20 cells/ul after 5 days of mobilization with G-CSF alone will achieve > or equal to 2 X 10(6)CD34+ cells/kg within 3 days of apheresis after receiving Plerixafor with G-CSF.

Condition	Intervention	Phase
Multiple Myeloma Non-Hodgkins Lymphoma Hodgkins Disease	Drug: G-CSF plus Plerixafor	Phase 2


Study Type:	Interventional
Study Design:	Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Plerixafor Rescue Mobilization For Autologous Stem Cell Transplant Patients With Inadequate Response to G-CSF

Resource links provided by NLM:

MedlinePlus related topics: Lymphoma

Drug Information available for: Plerixafor

Genetic and Rare Diseases Information Center resources: Hodgkin Lymphoma Lymphosarcoma Multiple Myeloma

U.S. FDA Resources

Further study details as provided by Duke University:

Primary Outcome Measures:

Number of Participants Who Achieved > or Equal to 2 X 10(6)CD34+ Cells/kg Within 3 Days of Apheresis After Receiving Plerixafor With G-CSF. [ Time Frame: 5 days after receiving G-CSF ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Number of Participants Experiencing a Grade III/IV Toxicity [ Time Frame: 6 months post transplant or until relapse ] [ Designated as safety issue: Yes ]
Safety of plerixafor as measured by Grade III/IV Toxicity
Number of Subjects Experiencing Graft Failure [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
To investigate the hematological activity of Plerixafor as measured by Graft Failure. Graft failure is defined as failure of initial engraftment (primary graft failure) or initial engraftment, but subsequent loss of hematopoiesis (secondary graft failure).
Days to Absolute Neutrophil Count >500 [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
Number of Subjects Experiencing Durability of Engraftment [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
Durability of engraftment is defined as the duration and stability of hematopoiesis following autologous transplantation. Subjects who experience durable engraftment have neutrophil counts greater than 500 and platelet counts greater than 20,000 within the specified time frame.
Platelet Engraftment [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
Days to platelet count >20,000


Enrollment:	21
Study Start Date:	May 2009
Study Completion Date:	May 2013
Primary Completion Date:	August 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: G-CSF plus Plerixafor Patients who were unable to mobilize a minimum number of cells (CD34+ cell count <20 cells/ul)following 5 days of G-CSF mobilization.	Drug: G-CSF plus Plerixafor On Day 5 of G-CSF mobilization, if the patient's peripheral CD34+ cell count is < 7cells/µl then 240ug/kg Plerixafor will be given in the evening prior to receiving 10µg/kg G-CSF and undergoing apheresis the next morning for up to 3 days of apheresis or until ≥ 5x10(6) cells/kg are collected. if the patient's peripheral CD34+ cell count is 7 to 19 cells/ul (inclusive), apheresis will be done. If the apheresis yield is < 1.3x10(6) CD34+ cells/kg then 240ug/kg Plerixafor will be given in the evening prior to receiving 10 µg/kg G-CSF and undergoing apheresis the next morning. If the apheresis yield is at least double that on Day 5, Plerixafor followed the next morning by G-CSF and apheresis will be repeated for up to a total of 3 days of apheresis or until 5x10(6) cells/kg are collected. Other Name: Mozobil, AMD3100

Arms

Assigned Interventions

Experimental: G-CSF plus Plerixafor

Patients who were unable to mobilize a minimum number of cells (CD34+ cell count <20 cells/ul)following 5 days of G-CSF mobilization.

Drug: G-CSF plus Plerixafor

On Day 5 of G-CSF mobilization,

if the patient's peripheral CD34+ cell count is < 7cells/µl then 240ug/kg Plerixafor will be given in the evening prior to receiving 10µg/kg G-CSF and undergoing apheresis the next morning for up to 3 days of apheresis or until ≥ 5x10(6) cells/kg are collected.
if the patient's peripheral CD34+ cell count is 7 to 19 cells/ul (inclusive), apheresis will be done. If the apheresis yield is < 1.3x10(6) CD34+ cells/kg then 240ug/kg Plerixafor will be given in the evening prior to receiving 10 µg/kg G-CSF and undergoing apheresis the next morning. If the apheresis yield is at least double that on Day 5, Plerixafor followed the next morning by G-CSF and apheresis will be repeated for up to a total of 3 days of apheresis or until 5x10(6) cells/kg are collected.

Other Name: Mozobil, AMD3100

Detailed Description:

This is a single-center, Phase 2, open-label study. All patients diagnosed with non-hodgkins lymphoma, hodgkins disease or multiple myeloma and candidates for autologous transplantation are eligible to enter into the study. The only change to the standard of care is the addition of 240 ug/kg Plerixafor following 5 days of (G-CSF) mobilization.

The results of the study will provide both numeric and categorical estimates of measurements of the safety and efficacy of Plerixafor. The primary efficacy endpoint, Treatment Success, is a binary response variable categorizing whether the patient was able to mobilize at least 2 X 10(6) CD34+ cells/kg within 3 days of apheresis.

The percentage of patients achieving Treatment Success will be summarized. All AEs will be followed for 30 days after the last apheresis or until the first dose of ablative chemotherapy, whichever occurs first. All SAEs will be followed for 6 months post-transplant or until relapse. All patients who receive at least one dose of Plerixafor will be included in all summaries of AEs.

Eligibility


Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age 18 to 75 years.
Diagnosis of NHL, HD or MM
Eligible for autologous transplantation
CD34+ cell count < 7 cells/ul after 5 days of mobilization with G-CSF or CD34+ cell count between 7 and 19 (inclusive) on day 5 of mobilization with G-CSF and < 1.3 x 106 CD34+ cells collected by apheresis on day 5 of G-CSF therapy.
< or equal to 5 prior regimens of chemotherapy (Rituxan is not considered chemotherapy for the purpose of this study)
≥ 3 weeks since last cycle of chemotherapy and the beginning of G-CSF mobilization (Rituxan and Lenalidomide are not considered chemotherapy for the purpose of this study)
Total dose of melphalan < or equal to 200 mg
ECOG performance status of 0 or 1
Recovered from all acute toxic effects of prior chemotherapy
Absolute PMN count > 1.0 X 10(9)/l prior to first dose of G-CSF
PLT count > 75 X 10(9)/l prior to first dose of G-CSF
Serum creatinine < or equal to 2.5 mg/dl
SGOT, SGPT and total bilirubin < 2 X upper limit of normal (ULN) prior to the first dose of G-CSF
Cardiac and pulmonary status sufficient to undergo apheresis and transplantation as determined by standard institutional practice
Signed informed consent
Patients of childbearing potential agree to use an approved form of contraception

Exclusion Criteria:

A co-morbid condition which, in the view of the investigator, renders the patient at high risk from treatment complications
Failed previous stem cell collection or collection attempts
A residual acute medical condition resulting from prior chemotherapy
Active brain metastases or carcinomatous meningitis
Active infection requiring antibiotic treatment (excluding controlled catheter-related bacteremia)
Received prior radio-immunotherapy with Zevalin or Bexxar
Received thalidomide, dexamethasone, and/or Velcade within 7 days prior to the first dose of G-CSF
Positive pregnancy test in female patients
Lactating females
Patients who previously received experimental therapy within 4 weeks of enrolling in this protocol

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00901225

Locations


United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27705

Sponsors and Collaborators

Duke University

Genzyme, a Sanofi Company

Investigators


Principal Investigator:	Mitchell Horwitz, MD	Duke University

More Information

No publications provided


Responsible Party:	Duke University
ClinicalTrials.gov Identifier:	NCT00901225 History of Changes
Other Study ID Numbers:	Pro00014563
Study First Received:	May 4, 2009
Results First Received:	October 30, 2013
Last Updated:	April 8, 2014
Health Authority:	United States: Institutional Review Board

Keywords provided by Duke University:


NHL

Additional relevant MeSH terms:


Lymphoma, Non-Hodgkin Immune System Diseases Immunoproliferative Disorders Lymphatic Diseases Lymphoma Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type	JM 3100 Anti-HIV Agents Anti-Infective Agents Anti-Retroviral Agents Antiviral Agents Pharmacologic Actions Therapeutic Uses

ClinicalTrials.gov processed this record on February 27, 2015