Hodgkins Disease, Multiple Myeloma, Non-Hodgkins Lymphoma
Conditions
Keywords
NHL
Brief 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.
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.
Interventions
On Day 5 of G-CSF mobilization, 1. 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. 2. 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.
Sponsors
Genzyme, a Sanofi Company
Duke University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing a Grade III/IV Toxicity | 6 months post transplant or until relapse | Safety of plerixafor as measured by Grade III/IV Toxicity |
| Number of Subjects Experiencing Graft Failure | 12 months | 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 | 12 months | — |
| Number of Subjects Experiencing Durability of Engraftment | 12 months | 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 | 12 months | Days to platelet count \>20,000 |
Countries
United States
Participant flow
Recruitment details
The first patient was enrolled in April 2005 and the final patient enrolled in August 2010. The protocol was closed to accrual for approximately 3.5yrs, so the total time to protocol activation was 15 months. This was a single institution study (Duke adult stem cell transplant program).
Pre-assignment details
All patients deemed to be poor mobilizers to G-CSF as a single agent, were eligible for enrollment (assuming protocol eligibility criteria were met).
Participants by arm
| Arm | Count |
|---|---|
| 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. | 21 |
| Total | 21 |
Baseline characteristics
| Characteristic | G-CSF Plus Plerixafor |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 9 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Age, Continuous | 61 years STANDARD_DEVIATION 9 |
| Region of Enrollment United States | 21 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 4 / 21 |
| serious Total, serious adverse events | 0 / 21 |
Outcome results
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.
Time frame: 5 days after receiving G-CSF
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| G-CSF Plus Plerixafor | 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. | 15 participants |
Secondary
Days to Absolute Neutrophil Count >500
Time frame: 12 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| G-CSF Plus Plerixafor | Days to Absolute Neutrophil Count >500 | 11 days |
Secondary
Number of Participants Experiencing a Grade III/IV Toxicity
Safety of plerixafor as measured by Grade III/IV Toxicity
Time frame: 6 months post transplant or until relapse
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| G-CSF Plus Plerixafor | Number of Participants Experiencing a Grade III/IV Toxicity | 0 participants |
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.
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| G-CSF Plus Plerixafor | Number of Subjects Experiencing Durability of Engraftment | 20 participants |
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).
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| G-CSF Plus Plerixafor | Number of Subjects Experiencing Graft Failure | 0 participants |
Secondary
Platelet Engraftment
Days to platelet count \>20,000
Time frame: 12 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| G-CSF Plus Plerixafor | Platelet Engraftment | 19 days |