Study of Plerixafor for Rescue of Poor Mobilizers in Autologous Stem Cell Transplant

Multiple Myeloma Clinical Trial

Official title:

Plerixafor Rescue Mobilization For Autologous Stem Cell Transplant Patients With Inadequate Response to G-CSF

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00901225
• Other study ID #: Pro00014563
• Status: Completed
• Phase: Phase 2
• First received: May 4, 2009
• Last updated: April 8, 2014
• Start date: May 2009
• Est. completion date: May 2013

Study information

• Verified date: April 2014
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: May 2013
• Est. primary completion date: August 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hodgkin Disease
• Hodgkins Disease
• Lymphoma, Non-Hodgkin
• Multiple Myeloma
• Non-Hodgkins Lymphoma

Intervention

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.

Locations

Country	Name	City	State
United States	Duke University Medical Center	Durham	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Duke University	Genzyme, a Sanofi Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		5 days after receiving G-CSF	No
Secondary	Number of Participants Experiencing a Grade III/IV Toxicity	Safety of plerixafor as measured by Grade III/IV Toxicity	6 months post transplant or until relapse	Yes
Secondary	Number of Subjects Experiencing Graft Failure	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).	12 months	Yes
Secondary	Days to Absolute Neutrophil Count >500		12 months	Yes
Secondary	Number of Subjects Experiencing Durability of Engraftment	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.	12 months	Yes
Secondary	Platelet Engraftment	Days to platelet count >20,000	12 months	Yes