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TerminatedNCT01408043Updated Jun 14, 2019Results posted

Etoposide, Filgrastim, and Plerixafor in Improving Stem Cell Mobilization in Treating Patients With Non-Hodgkin Lymphoma

An interventional study of plerixafor and filgrastim in Adult Acute Lymphoblastic Leukemia in Remission, Adult Grade III Lymphomatoid Granulomatosis and Adult Nasal Type Extranodal NK/T-cell Lymphoma, sponsored by Case Comprehensive Cancer Center. Terminated at 1 site in United States. Open to participants aged 18 Years to 78 Years. Per ClinicalTrials.gov, last updated 2019-06-14.

Sponsored by Case Comprehensive Cancer Center · Not applicable, Interventional, and Treatment

Why this study was terminated
Slow Accrual
Phase
Not applicable
Study type
Interventional
Enrollment
25
Allocation
Not applicable
Ages
18 Years to 78 Years
Sex
All
01

Study summary

This clinical trial studies etoposide, filgrastim and plerixafor in improving stem cell mobilization in patients with non-Hodgkin lymphoma. Giving colony-stimulating factors, such as filgrastim, and plerixafor and etoposide together helps stem cells move from the patient's bone marrow to the blood so they can be collected and stored.

Read the detailed description

PRIMARY OBJECTIVES:

I. To determine whether the addition of plerixafor improves the proportion of patients with lymphoma who collect >= 8 x 10\^6 cluster of differentiation (CD)34+ cells/kg within two days by 25% compared to the historical estimate of 42% with etoposide and G-CSF (filgrastim).

II. To determine whether patients achieving collection of >= 8 x 10\^6 CD34+ cells/kg have a 15% one year survival advantage relative to the historical estimate of 68% among patients mobilizing >= 2 but \< 8 x 10\^6 CD34+ cells/kg with etoposide and G-CSF.

SECONDARY OBJECTIVES:

I. To demonstrate that patients receiving >= 8 x 10\^6 CD34+ cells/kg have more rapid neutrophil and platelet recovery and earlier hospital discharge than those receiving \< 8 x 10\^6 CD 34+ cells/kg.

II. To compare overall survival and progression-free survival between patients receiving >= 8 x 10\^6 CD34+ cells/kg and those receiving \< 8 x 10\^6 CD34+ cells/kg.

III. To compare number of days of apheresis required to achieve goal, transfusion requirements, hospitalization costs, need for remobilization between groups.

IV. To evaluate whether peripheral CD34+ cell count correlates with graft content of CD34+ cells.

OUTLINE:

Patients receive etoposide intravenously (IV) over 4 hours on day 0, filgrastim subcutaneously (SC) once daily (QD) beginning day 1, and plerixafor SC 15-18 hours prior to apheresis. Patients unable to achieve target collection of >= 8 x 10\^6 CD34+ cells/kg receive another dose of plerixafor followed by apheresis. Following the second apheresis, patients achieving =\< 2 x 10\^6 CD34+ cells/kg may continue filgrastim with plerixafor and continue collection according to the attending physician.

After completion of study treatment, patients are followed up at 28 days and then for at least 1 year.

02

Conditions studied

  • Adult Acute Lymphoblastic Leukemia in Remission
  • Adult Grade III Lymphomatoid Granulomatosis
  • Adult Nasal Type Extranodal NK/T-cell Lymphoma
  • Anaplastic Large Cell Lymphoma
  • Angioimmunoblastic T-cell Lymphoma
  • Cutaneous B-cell Non-Hodgkin Lymphoma
  • Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
  • Hepatosplenic T-cell Lymphoma
  • Nodal Marginal Zone B-cell Lymphoma
  • Noncutaneous Extranodal Lymphoma
  • Peripheral T-cell Lymphoma
  • Recurrent Adult Burkitt Lymphoma
  • Recurrent Adult Diffuse Large Cell Lymphoma
  • Recurrent Adult Diffuse Mixed Cell Lymphoma
  • Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
  • Recurrent Adult Grade III Lymphomatoid Granulomatosis
  • Recurrent Adult Immunoblastic Large Cell Lymphoma
  • Recurrent Adult Lymphoblastic Lymphoma
  • Recurrent Adult T-cell Leukemia/Lymphoma
  • Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
  • Recurrent Grade 1 Follicular Lymphoma
  • Recurrent Grade 2 Follicular Lymphoma
  • Recurrent Grade 3 Follicular Lymphoma
  • Recurrent Mantle Cell Lymphoma
  • Recurrent Marginal Zone Lymphoma
  • Recurrent Mycosis Fungoides/Sezary Syndrome
  • Recurrent Small Lymphocytic Lymphoma
  • Refractory Chronic Lymphocytic Leukemia
  • Refractory Hairy Cell Leukemia
  • Small Intestine Lymphoma
  • Splenic Marginal Zone Lymphoma
  • T-cell Large Granular Lymphocyte Leukemia
  • Testicular Lymphoma
  • Waldenström Macroglobulinemia
03

Who can participate

Ages eligible
18 Years to 78 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Have biopsy-confirmed non-Hodgkin lymphoma, of any type
  • Must be eligible for autologous transplantation according to institutional guidelines
  • Eastern Cooperative Oncology Group performance status of 0 or 1
  • Karnofsky performance status of 70 to 100
  • Negative for human immunodeficiency virus (HIV)
  • prior to the start of mobilization, subjects must have:

    • Absolute neutrophil count of >= 1.2 x 10\^9/L
    • Platelet count of >= 100 x 10\^9/L
    • Creatinine clearance >= 30 mL/minute
  • All patients must be able to comprehend and sign informed consent
  • If childbearing potential must either agree to complete abstinence from heterosexual intercourse or effective means of contraception during stem cell mobilization and for at least 3 months following last plerixafor dose; female patients will undergo pregnancy test prior to stem cell mobilization therapy

Exclusion criteria

Exclusion Criteria:

  • Have had previous transplants and/or prior mobilization attempts
  • Have evidence of progressive non-Hodgkin lymphoma
  • Have evidence of bone marrow involvement of lymphoma at time of transplant staging
  • Had evidence of active central nervous system (CNS) involvement
  • Have had previous radiation of the pelvic area
  • Have had prior radioimmunotherapy
  • Have received experimental therapy within 2 weeks of enrollment
  • Be currently enrolled in another investigational protocol
  • Have prior history of other malignancies, excluding basal cell carcinoma or squamous cell carcinoma of the skin
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
25 participants (actual)

Study arms

  • Experimental
    Treatment (stem cell supermobilization)

    Patients receive etoposide IV over 4 hours on day 0, filgrastim SC QD beginning day 1, and plerixafor SC 15-18 hours prior to apheresis. Patients unable to achieve target collection of \>= 8 x 10\^6 CD34+ cells/kg receive another dose of plerixafor followed by apheresis. Following the second apheresis, patients achieving =\< 2 x 10\^6 CD34+ cells/kg may continue filgrastim with plerixafor and continue collection according to the attending physician.

    Drug: plerixafor · Biological: filgrastim · Drug: etoposide · Procedure: leukapheresis

Interventions

  • Drugplerixafor

    Given SC

    Also known as: AMD 3100, Mozobil

  • Biologicalfilgrastim

    Given SC

    Also known as: G-CSF, Neupogen

  • Drugetoposide

    Given IV

    Also known as: EPEG, VP-16, VP-16-213

  • Procedureleukapheresis

    Undergo apheresis

05

What researchers measure

Primary outcomes

  1. Collection Using Plerixafor, Etoposide, and Filgrastim

    Number of participants able to collect equal to or more than 8 x 10\^6 CD34+ cells/kg with addition of plerixafor to etoposide and filgrastim. These participants are defined as supermobilizers. Participants with less than 8 x 10\^6 CD34+ cells/kg are defined as normal mobilizers.

    Time frame: Within 2 days of apheresis

  2. Progression-free Survival

    The number of participants of patients who receive greater than or equal to 8 x 10\^6 CD34+ cells/kg following collection with plerixafor, etoposide, and filgrastim and that have progression-free survival at one year

    Time frame: Up to 1 year post-transplant

  3. Overall Survival

    Number of participants who receive greater than or equal to 8 x 10\^6 CD34+ cells/kg by 15% following collection with plerixafor, etoposide, and filgrastimstill alive at 1 yr post transplant

    Time frame: Up to 1 year post-transplant

Secondary outcomes

  1. Neutrophil Recovery in Super Mobilizers and Normal Mobilizers

    Neutrophil recovery in participants receiving greater than or equal to 8 and less than 8 x 10\^6 CD34+ cells/kg entered as the mean cell count of super mobilizers and normal mobilizers.

    Time frame: Up to 28 days post treatment

  2. Platelet Recovery in Super Mobilizers and Normal Mobilizers

    Platelet recovery in participants receiving greater than or equal to 8 and less than 8 x 10\^6 CD34+ cells/kg.

    Time frame: Up to 28 days post treatment

  3. Length of Hospital Stay in Super Mobilizers and Normal Mobilizers

    Length of hospital stay in participants receiving greater than or equal to 8 and less than 8 x 10\^6 CD34+ cells/kg.

    Time frame: Up to 28 days post treatment

  4. Progression-free Survival in Supermobilizers and Normal Mobilizers

    Percentage of participants who were alive and free of progression 1 year after transplant (PFS)

    Time frame: Up to 1 year post-transplant

  5. Overall Survival in Supermobilizers and Normal Mobilizers

    Percentage of participants who were alive 1 year after transplant (OS)

    Time frame: Up to 1 year post-transplant

  6. Number of Days of Apheresis Required

    Number of days of apheresis required to achieve goal in supermobilizers and normal mobilizers

    Time frame: Up to 28 days post treatment

  7. Number of Transfusion Requirements

    Number of transfusions (number of packed red blood cells and platelet transfusions required from day 0 to +28 post-transplant) in supermobilizers and normal mobilizers

    Time frame: Up to 28 days post treatment

  8. Need for Remobilization

    Number of participants that needed remobilization in supermobilizers and normal mobilizers. Remobilization can be described as follows: The first step for patients undergoing autologous hematopoietic cell transplantation is to mobilize hematopoietic progenitor/stem cells from the bone marrow using G-CSF, plerixafor and/or chemotherapy. This is followed by collection of the cells by apheresis. If sufficient number of progenitor/stem cells cannot be mobilized and then collected by apheresis to proceed with transplantation, it is considered as "mobilization failure". For these patients, mobilization of their hematopoietic progenitor/stem cells is attempted a second time ("remobilization"). The need to do a second 'mobilization' attempt is not ideal.

    Time frame: Up to 28 days post treatment

  9. Correlation of Peripheral CD34+ Cell Count With Graft Content of CD34+ Cells

    Correlation of peripheral CD34+ cell count with graft content of CD34+ cells assessed using Spearman correlation.

    Time frame: Up to 28 days post treatment

06

Results

Posted Jun 14, 2019

Participant flow

Participant flow — Overall Study
MilestoneTreatment (Stem Cell Supermobilization)
Started25
Completed24
Not completed1
Withdrew: Unable to collect cells1

Outcome measures

PrimaryCollection Using Plerixafor, Etoposide, and Filgrastim

Number of participants able to collect equal to or more than 8 x 10\^6 CD34+ cells/kg with addition of plerixafor to etoposide and filgrastim. These participants are defined as supermobilizers. Participants with less than 8 x 10\^6 CD34+ cells/kg are defined as normal mobilizers.

Time frame:
Within 2 days of apheresis
Reported as:
Count of participants · Participants
Collection Using Plerixafor, Etoposide, and Filgrastim
ParticipantsTreatment (Stem Cell Supermobilization)
Supermobilizers7
Normal Mobilizers17
Non mobilizers1
PrimaryProgression-free Survival

The number of participants of patients who receive greater than or equal to 8 x 10\^6 CD34+ cells/kg following collection with plerixafor, etoposide, and filgrastim and that have progression-free survival at one year

Time frame:
Up to 1 year post-transplant
Reported as:
Count of participants · Participants
Progression-free Survival
ParticipantsTreatment (Stem Cell Supermobilization)
Progression-free Survival7
PrimaryOverall Survival

Number of participants who receive greater than or equal to 8 x 10\^6 CD34+ cells/kg by 15% following collection with plerixafor, etoposide, and filgrastimstill alive at 1 yr post transplant

Time frame:
Up to 1 year post-transplant
Reported as:
Count of participants · Participants
Overall Survival
ParticipantsTreatment (Stem Cell Supermobilization)
Overall Survival7
SecondaryNeutrophil Recovery in Super Mobilizers and Normal Mobilizers

Neutrophil recovery in participants receiving greater than or equal to 8 and less than 8 x 10\^6 CD34+ cells/kg entered as the mean cell count of super mobilizers and normal mobilizers.

Time frame:
Up to 28 days post treatment
Reported as:
Mean · K/ul
Neutrophil Recovery in Super Mobilizers and Normal Mobilizers
K/ulTreatment (Stem Cell Supermobilization)
Supermobilizers10.3 ± 0.5
Normal Mobilizers10.2 ± 0.7
SecondaryPlatelet Recovery in Super Mobilizers and Normal Mobilizers

Platelet recovery in participants receiving greater than or equal to 8 and less than 8 x 10\^6 CD34+ cells/kg.

Time frame:
Up to 28 days post treatment
Reported as:
Mean · percentage of change
Platelet Recovery in Super Mobilizers and Normal Mobilizers
percentage of changeTreatment (Stem Cell Supermobilization)
Supermobilizers20.9 ± 6.5
Normal Mobilizers19.8 ± 5.6
SecondaryLength of Hospital Stay in Super Mobilizers and Normal Mobilizers

Length of hospital stay in participants receiving greater than or equal to 8 and less than 8 x 10\^6 CD34+ cells/kg.

Time frame:
Up to 28 days post treatment
Reported as:
Mean · days
Length of Hospital Stay in Super Mobilizers and Normal Mobilizers
daysTreatment (Stem Cell Supermobilization)
Supermobilizers20.7 ± 0.5
Normal Mobilizers22.5 ± 5.5
SecondaryProgression-free Survival in Supermobilizers and Normal Mobilizers

Percentage of participants who were alive and free of progression 1 year after transplant (PFS)

Time frame:
Up to 1 year post-transplant
Reported as:
Number · percent of participants
Progression-free Survival in Supermobilizers and Normal Mobilizers
percent of participantsTreatment (Stem Cell Supermobilization)
Supermobilizers100
Normal Mobilizers82
SecondaryOverall Survival in Supermobilizers and Normal Mobilizers

Percentage of participants who were alive 1 year after transplant (OS)

Time frame:
Up to 1 year post-transplant
Reported as:
Number · percent of participants
Overall Survival in Supermobilizers and Normal Mobilizers
percent of participantsTreatment (Stem Cell Supermobilization)
Supermobilizers100
Normal Mobilizers100
SecondaryNumber of Days of Apheresis Required

Number of days of apheresis required to achieve goal in supermobilizers and normal mobilizers

Time frame:
Up to 28 days post treatment
Reported as:
Mean · days
Number of Days of Apheresis Required
daysTreatment (Stem Cell Supermobilization)
Supermobilizers1.1 ± 0.4
Normal Mobilizers2.9 ± 1.1
SecondaryNumber of Transfusion Requirements

Number of transfusions (number of packed red blood cells and platelet transfusions required from day 0 to +28 post-transplant) in supermobilizers and normal mobilizers

Time frame:
Up to 28 days post treatment
Reported as:
Mean · transfusions
Number of Transfusion Requirements
transfusionsTreatment (Stem Cell Supermobilization)
Supermobilizers3.7 ± 2.1
Normal Mobilizers4.4 ± 2.0
SecondaryNeed for Remobilization

Number of participants that needed remobilization in supermobilizers and normal mobilizers. Remobilization can be described as follows: The first step for patients undergoing autologous hematopoietic cell transplantation is to mobilize hematopoietic progenitor/stem cells from the bone marrow using G-CSF, plerixafor and/or chemotherapy. This is followed by collection of the cells by apheresis. If sufficient number of progenitor/stem cells cannot be mobilized and then collected by apheresis to proceed with transplantation, it is considered as "mobilization failure". For these patients, mobilization of their hematopoietic progenitor/stem cells is attempted a second time ("remobilization"). The need to do a second 'mobilization' attempt is not ideal.

Time frame:
Up to 28 days post treatment
Reported as:
Count of participants · Participants
Need for Remobilization
ParticipantsTreatment (Stem Cell Supermobilization)
Supermobilizers0
Normal Mobilizers0
SecondaryCorrelation of Peripheral CD34+ Cell Count With Graft Content of CD34+ Cells

Correlation of peripheral CD34+ cell count with graft content of CD34+ cells assessed using Spearman correlation.

Time frame:
Up to 28 days post treatment

No measurements were reported for this outcome.

Adverse events

Collected over Up to 1 year post-transplant. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Treatment (Stem Cell Supermobilization)0/25 (0%)0/25 (0%)0/25 (0%)

Baseline characteristics

Participants enrolled and received intervention.

Age, Continuous
Age, Continuous(years)Treatment (Stem Cell Supermobilization)
Mean62.48 ± 11.14
Sex: Female, Male
Sex: Female, Male(Participants)Treatment (Stem Cell Supermobilization)
Female4
Male21
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Treatment (Stem Cell Supermobilization)
Hispanic or Latino0
Not Hispanic or Latino25
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Treatment (Stem Cell Supermobilization)
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American2
White23
More than one race0
Unknown or Not Reported0
Region of Enrollment
Region of Enrollment(participants)Treatment (Stem Cell Supermobilization)
United States25
07

Study locations

1 site
  • Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
    Cleveland, Ohio 44195, United States
08

Registry details

Key details

Study ID
NCT01408043
Lead sponsor
Case Comprehensive Cancer Center
Collaborators
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Aug 3, 2011
Start date
Oct 2011
Primary completion
May 2016
Completion
May 2016
Results posted
Jun 14, 2019
Last update
Jun 14, 2019

Study contacts

Navneet Majhail, MD
principal investigator · Case Comprehensive Cancer Center

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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