Plerixafor for Stem Cell Mobilization in Normal Donors
Study Details
Study Description
Brief Summary
The goal of this clinical research study is to learn if treating stem cell donors with filgrastim (G-CSF) and plerixafor (Mozobil®) can cause them to produce a higher number of blood stem cells than filgrastim by itself. Researchers also want to learn if giving both of these drugs helps donors produce enough stem cells so that only 1 apheresis procedure needs to be performed.
Researchers will study if using both drugs lowers the risk of the stem cell transplant recipients developing severe forms graft-versus-host disease (GVHD). GVHD is a condition in which transplanted tissue (such as blood stem cells) attacks the tissue of the recipient's body.
The safety and effectiveness of this drug combination will also be studied.
Filgrastim and plerixafor are both designed to help move or "mobilize" the stem cells from the bone marrow to the blood.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
Stem Cell Transplant:
You will receive blood stem cells from a donor on this study. You will sign a separate informed consent for the transplant procedure.
Follow-Up Visits:
About 1, 3, and 6 months after the transplant, an extra sample of bone marrow (about 2 teaspoons) will be collected at the same time as the standard of care bone marrow aspiration/biopsy procedures. This bone marrow sample will be tested to find out how well the donated stem cells have been accepted by your body. However, you will not have a separate bone marrow aspiration/biopsy only to collect bone marrow for this testing.
When you return to the clinic at 6, 9, and 12 months for routine transplant follow-up visits, the study staff will try to get information on your health status from the clinic notes in your medical record. If this is not possible, you may receive a phone call from the study staff to check your health status. These calls will last about 10 minutes.
Length of Treatment:
You will be on study for about 1 year after the transplant (including follow-up contact by phone, if needed).
You may be taken off study early if you are not able to follow study directions or if you decide to leave the study.
This is an investigational study. Filgrastim is FDA approved for use in stem cell collection. Plerixafor is FDA approved for use in patients with multiple myeloma and non-Hodgkin's lymphoma.
Up to 30 donor and recipient pairs will take part in this study. All will be enrolled at MD Anderson.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Filgrastim + Plerixafor Each donor receives Filgrastim 5 µg/kg subcutaneously in the morning daily for 4 days. The dose of Filgrastim based on the donor's actual body weight. Donors will continue Filgrastim until completion of apheresis. Each donor receives Plerixafor 240 µg/kg subcutaneously in the evening on the fourth day of Filgrastim mobilization. The dose-volume of Plerixafor based on the donor's actual body weight. Apheresis procedure to start the morning of day 5, approximately 10 to 11 hours after the administration of Plerixafor. The apheresis procedure will start in the morning of day 5, approximately 10 to 11 hours after the administration of Plerixafor. The apheresis procedure may continue beyond day 1 until the target dose of 4x106 cluster of differentiation 34 (CD34+) cells/kg (recipient's weight) is obtained. |
Drug: Filgrastim
5 µg/kg in the morning daily for 4 days.
Other Names:
Drug: Plerixafor
240 µg/kg subcutaneously in the evening on the fourth day of Filgrastim mobilization.
Other Names:
Procedure: Apheresis Procedure
The apheresis procedure will start in the morning of day 5, approximately 10 to 11 hours after the administration of Plerixafor.
The apheresis procedure may continue beyond day 1 until the target dose of 4x106 CD34+ cells/kg (recipient's weight) is obtained.
|
Outcome Measures
Primary Outcome Measures
- Summary of Most Common Toxicity: Donor Safety in Mobilizing Peripheral Blood Progenitor Cells (PBPC) [5 days]
Primary safety endpoint is the development of any unexpected toxicity (any grade 2 or higher non-hematologic toxicity) in donors. The severity of the toxicity - adverse events (AEs) graded according to Common Terminology Criteria v4.0 (CTCAE).
- Feasibility in Mobilizing PBPC in Donors: Number of Donors Reaching Stem Cell Target Collection on First Day of Collection Following Treatment of Filgrastim Plus Plerixafor [4 days]
Study determined to be feasible if all donors were able to receive Plerixafor without developing any grade 2 or higher non-hematologic toxicity. Feasibility of the combination of Filgrastim, Granulocyte-colony stimulating factor (G-CSF) plus Plerixafor is to effectively mobilize CD34+ cells so that an adequate transplant (>4 x 10^6 CD34+ cells/kg) can be reliably collected with one apheresis for allogeneic HSCT.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Donor eligibility: Age >/= 10 years.
-
Donor eligibility: Related donors who met standard eligibility criteria and are willing to participate in this study.
-
Donor eligibility: Able to provide informed consent.
-
Recipient Eligibility: Patients who are scheduled to undergo an allogeneic related transplant and whose donors consented to participate in this study.
-
Recipient Eligibility: Able to provide informed consent.
Exclusion Criteria:
- Donors who are on anti-coagulation or anti-platelet agents are not eligible.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Texas MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- M.D. Anderson Cancer Center
- Proteonomix, Inc.
Investigators
- Principal Investigator: Chitra M. Hosing, MD, M.D. Anderson Cancer Center
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 2012-0579
- NCI-2013-02209
Study Results
Participant Flow
| Recruitment Details | Recruitment Period: October 16, 2013 to May 1, 2015. All recruitment done at The University of Texas MD Anderson Cancer Center. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Filgrastim + Plerixafor for Donors | Recipients |
|---|---|---|
| Arm/Group Description | Filgrastim 5 µg/kg subcutaneously daily for 4 days until end of apheresis; Plerixafor 240 µg/kg subcutaneously on fourth day of Filgrastim mobilization; followed by Apheresis day 5 which may continue beyond day 1 until target dose of 4x10^6 CD34+ cells/kg (recipient's weight) obtained. | Recipients received Plerixafor mobilized cells for allogeneic hematopoietic stem cell transplantation (HSCT) on day 0 of their designated treatment plan (following day 5 of donor's Plerixafor study specific treatment plan). |
| Period Title: Overall Study | ||
| STARTED | 11 | 11 |
| COMPLETED | 7 | 5 |
| NOT COMPLETED | 4 | 6 |
Baseline Characteristics
| Arm/Group Title | Donors Filgrastim + Plerixafor | Recipients | Total |
|---|---|---|---|
| Arm/Group Description | Filgrastim 5 µg/kg subcutaneously daily for 4 days until end of apheresis; Plerixafor 240 µg/kg subcutaneously on fourth day of Filgrastim mobilization; followed by Apheresis day 5 which may continue beyond day 1 until target dose of 4x10^6 CD34+ cells/kg (recipient's weight) obtained. | Recipients received Plerixafor mobilized cells on day 0 of their designated treatment plan (following day 5 of donor's Plerixafor study specific treatment plan). | Total of all reporting groups |
| Overall Participants | 11 | 11 | 22 |
| Age (years) [Median (Full Range) ] | |||
| Median (Full Range) [years] |
58
|
58
|
58
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
7
63.6%
|
5
45.5%
|
12
54.5%
|
| Male |
4
36.4%
|
6
54.5%
|
10
45.5%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
3
27.3%
|
3
27.3%
|
6
27.3%
|
| White |
8
72.7%
|
8
72.7%
|
16
72.7%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
11
100%
|
11
100%
|
22
100%
|
Outcome Measures
| Title | Summary of Most Common Toxicity: Donor Safety in Mobilizing Peripheral Blood Progenitor Cells (PBPC) |
|---|---|
| Description | Primary safety endpoint is the development of any unexpected toxicity (any grade 2 or higher non-hematologic toxicity) in donors. The severity of the toxicity - adverse events (AEs) graded according to Common Terminology Criteria v4.0 (CTCAE). |
| Time Frame | 5 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Donors: Filgrastim + Plerixafor |
|---|---|
| Arm/Group Description | Filgrastim 5 µg/kg subcutaneously daily for 4 days until end of apheresis; Plerixafor 240 µg/kg subcutaneously on fourth day of Filgrastim mobilization; followed by Apheresis day 5 which may continue beyond day 1 until target dose obtained. |
| Measure Participants | 11 |
| Tachycardia |
1
|
| Nausea |
2
|
| Insomnia |
2
|
| Bone pain |
2
|
| Injection site reaction |
1
|
| Diarrhea |
1
|
| Chest Pain |
1
|
| Title | Feasibility in Mobilizing PBPC in Donors: Number of Donors Reaching Stem Cell Target Collection on First Day of Collection Following Treatment of Filgrastim Plus Plerixafor |
|---|---|
| Description | Study determined to be feasible if all donors were able to receive Plerixafor without developing any grade 2 or higher non-hematologic toxicity. Feasibility of the combination of Filgrastim, Granulocyte-colony stimulating factor (G-CSF) plus Plerixafor is to effectively mobilize CD34+ cells so that an adequate transplant (>4 x 10^6 CD34+ cells/kg) can be reliably collected with one apheresis for allogeneic HSCT. |
| Time Frame | 4 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Four participants did not receive Plerixafor due to a white blood cell count outside of the protocol specific window. It should be noted, the protocol threshold for white blood cell count was amended from 40,000 to 45,000. |
| Arm/Group Title | Donors: Filgrastim + Plerixafor |
|---|---|
| Arm/Group Description | Filgrastim 5 µg/kg subcutaneously daily for 4 days until end of apheresis; Plerixafor 240 µg/kg subcutaneously on fourth day of Filgrastim mobilization; followed by Apheresis day 5 which may continue beyond day 1 until target dose obtained. |
| Measure Participants | 7 |
| Count of Participants [Participants] |
7
63.6%
|
Adverse Events
| Time Frame | Adverse event data collected for donors over one month period after first injection of filgrastim and for recipients from start of preparative regimen followed by infusion of allogeneic stem cell transplantation Day 0 to Day +30, up to 40 days. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | For the purpose of this study the treatment plan (preparative regimen followed by infusion of allogeneic stem cell transplantation) is defined as "transplant package"; therefore adverse events known to be caused by components of the transplant package and its direct consequences were collected. | |||
| Arm/Group Title | Donors Filgrastim + Plerixafor | Recipients | ||
| Arm/Group Description | Filgrastim 5 µg/kg subcutaneously daily for 4 days until end of apheresis; Plerixafor 240 µg/kg subcutaneously on fourth day of Filgrastim mobilization; followed by Apheresis day 5 which may continue beyond day 1 until target dose of 4x106 CD34+ cells/kg (recipient's weight) obtained. | Recipients received Plerixafor mobilized cells on day 0 of their designated treatment plan (following day 5 of donor's Plerixafor study specific treatment plan). | ||
All Cause Mortality |
||||
| Donors Filgrastim + Plerixafor | Recipients | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Donors Filgrastim + Plerixafor | Recipients | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/11 (0%) | 0/11 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Donors Filgrastim + Plerixafor | Recipients | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/11 (45.5%) | 7/11 (63.6%) | ||
| Blood and lymphatic system disorders | ||||
| Anemia | 1/11 (9.1%) | 1 | 0/11 (0%) | 0 |
| Cardiac disorders | ||||
| Mild tachicardia | 1/11 (9.1%) | 1 | 1/11 (9.1%) | 1 |
| Chest pain - cardiac | 1/11 (9.1%) | 1 | 0/11 (0%) | 0 |
| Eye disorders | ||||
| Dry eye | 0/11 (0%) | 0 | 1/11 (9.1%) | 1 |
| Gastrointestinal disorders | ||||
| Diarrhea | 1/11 (9.1%) | 1 | 3/11 (27.3%) | 3 |
| Mucositis oral | 0/11 (0%) | 0 | 5/11 (45.5%) | 5 |
| Nausea | 2/11 (18.2%) | 2 | 7/11 (63.6%) | 7 |
| General disorders | ||||
| Fever | 0/11 (0%) | 0 | 1/11 (9.1%) | 1 |
| Flu like symptoms | 0/11 (0%) | 0 | 3/11 (27.3%) | 3 |
| Nightsweats | 1/11 (9.1%) | 1 | 0/11 (0%) | 0 |
| Pain | 2/11 (18.2%) | 2 | 3/11 (27.3%) | 3 |
| Hepatobiliary disorders | ||||
| Elevated bilirubin | 0/11 (0%) | 0 | 2/11 (18.2%) | 2 |
| Immune system disorders | ||||
| Neutropenic fever | 0/11 (0%) | 0 | 2/11 (18.2%) | 2 |
| Infections and infestations | ||||
| CMV Reactivation, Alpha-hemalytic streptococcus bacteremia | 0/11 (0%) | 0 | 2/11 (18.2%) | 2 |
| Investigations | ||||
| Alanine aminotransferase increased | 0/11 (0%) | 0 | 2/11 (18.2%) | 2 |
| Blood bilirubin increased | 0/11 (0%) | 0 | 1/11 (9.1%) | 1 |
| Creatinine increased | 0/11 (0%) | 0 | 2/11 (18.2%) | 2 |
| Weight gain | 0/11 (0%) | 0 | 1/11 (9.1%) | 1 |
| Metabolism and nutrition disorders | ||||
| Hyperglycemia | 1/11 (9.1%) | 1 | 0/11 (0%) | 0 |
| Hypomagnesemia | 1/11 (9.1%) | 1 | 0/11 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| Bone pain | 2/11 (18.2%) | 2 | 0/11 (0%) | 0 |
| Nervous system disorders | ||||
| Headache | 1/11 (9.1%) | 1 | 0/11 (0%) | 0 |
| Altered mental status related to pain medication | 0/11 (0%) | 0 | 1/11 (9.1%) | 1 |
| Psychiatric disorders | ||||
| Insomnia | 2/11 (18.2%) | 2 | 2/11 (18.2%) | 2 |
| Renal and urinary disorders | ||||
| Cystitis noninfective | 0/11 (0%) | 0 | 1/11 (9.1%) | 1 |
| Fluid Overload | 0/11 (0%) | 0 | 1/11 (9.1%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Pneumonitis | 0/11 (0%) | 0 | 1/11 (9.1%) | 1 |
| Skin and subcutaneous tissue disorders | ||||
| Rash maculo-papular | 0/11 (0%) | 0 | 3/11 (27.3%) | 3 |
| Hand & foot syndrome | 0/11 (0%) | 0 | 2/11 (18.2%) | 2 |
| Surgical and medical procedures | ||||
| Injection site reaction | 1/11 (9.1%) | 1 | 0/11 (0%) | 0 |
| Vascular disorders | ||||
| Hypertension | 0/11 (0%) | 0 | 2/11 (18.2%) | 2 |
| Catheter related deep vein thrombosis (DTV) | 0/11 (0%) | 0 | 1/11 (9.1%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Chitra Hosing, MD/Professor, Stem Cell Transplantation |
|---|---|
| Organization | UT MD Anderson Cancer Center |
| Phone | 713-792-7734 |
| cmhosing@mdanderson.org |
- 2012-0579
- NCI-2013-02209