Evaluation of the Drug Plerixafor in Combination With Chemotherapy and G-CSF for Stem Cell Collection

• Sponsor: Emory University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01095757
• Collaborator: Genzyme, a Sanofi Company (Industry)
• Enrollment: 45
• Location: 1
• Arm: 1
• Duration (Months): 47.1
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

The purpose of this study is to test whether the addition of the drug plerixafor to treatment with chemotherapy and G-CSF can better activate your bone marrow stem cells to improve the chances of transplant. The study will look for the activation of a certain type of blood cell, called CD34+ cells in patients who receive plerixafor, chemotherapy and G-CSF. The investigators will follow the number of patients that achieve the target numbers of CD34+ cells. The number of patients achieving the target level of CD34+ cells, and the total number of CD34+ cells, will be compared to the numbers in previous studies testing just chemotherapy and G-CSF, without plerixafor.

The investigators will also test the safety of the combination of plerixafor with chemotherapy and G-CSF and look at the success of the transplantation after 12 months.

Condition or Disease	Intervention/Treatment	Phase
Myeloma; Lymphoma	Drug: Plerixafor	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 45 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Evaluation of Plerixafor (Mozobil ™, AMD3100) in Combination With Chemotherapy and G-CSF for CD34+ Cell Mobilization
• Study Start Date: Mar 1, 2010
• Actual Primary Completion Date: May 1, 2012
• Actual Study Completion Date: Feb 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Other: Plerixafor + Chemo and G-CSF Patients who receive a combination of Plerixafor, chemotherapy and G-CSF.	Drug: Plerixafor; 240 µg/kg subcutaneous injection on the day that the absolute neutrophil count (ANC) is > 1500/mm3 and on each day of apheresis for a total of 4 aphereses or the target CD34 cell dose has been reached.; Other Names: Mozobil AMD3100

Outcome Measures

Primary Outcome Measures

1. Patients Achieving Greater Than or Equal to 5 x 10^6 of CD34+ Cells/kg in a Single Day of Apheresis [Within the first 4 days following the first dose of Plerixafor]

2. Patients Achieving >= 3 X 10^6 CD34+ Cell/Kg [Within the first 4 days following the first dose of Plerixafor]

Secondary Outcome Measures

1. Average Number of Days for Engraftment (Engraftment Defined as Absolute Neutrophil Count>500) [Within the first 4 days following the first dose of Plerixafor]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Age 18-70 years

2. Multiple myeloma (MM) or non-Hodgkin's lymphoma (NHL) patients in first or second complete or partial remission

3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

4. Up to 3 prior treatment regimens

5. Meet all eligibility requirements for autologous transplant

6. Adequate marrow function defined as white blood cells (WBC) >3,000; ANC >1,500/mm3; platelets >75,000/mm3

7. Adequate renal function defined as creatinine clearance > 30 mL/min by Cockcroft-Gault

8. Adequate liver function defined as aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/bilirubin < 2 times upper limit of normal

9. Able to provide informed consent

10. Women not pregnant and agree to use contraception

Exclusion Criteria:

1. High risk co-morbidities for acute treatment complications (e.g., symptomatic coronary artery disease)

2. Brain metastases or carcinomatous meningitis

3. Previous treatment with high dose chemotherapy and autologous transplant

4. Previous attempt to collect B-hematopoietic progenitor cells (HPCs) following mobilization with growth factors alone, growth factors and chemotherapy, or plerixafor and growth factors

5. Acute infection or unexplained fever >38°C

6. Weight > 175% of ideal body weight as defined by the Devine equation

7. Experimental therapy within 4 weeks

8. Cytokine administration in the previous 14 days

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Emory University Winship Cancer Institute	Atlanta	Georgia	United States	30322

Sponsors and Collaborators

• Emory University
• Genzyme, a Sanofi Company

Investigators

• Principal Investigator: Edmund Waller, MD, PhD, Emory University Winship Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

• Cassens U, Momkvist PH, Zuehlsdorf M, Mohr M, Kienast J, Berdel WE, Sibrowski W. Kinetics of standardized large volume leukapheresis (LVL) in patients do not show a recruitment phenomenon of peripheral blood progenitor cells (PBPC). Bone Marrow Transplant. 2001 Jul;28(1):13-20.
• Christopher MJ, Rao M, Liu F, Woloszynek JR, Link DC. Expression of the G-CSF receptor in monocytic cells is sufficient to mediate hematopoietic progenitor mobilization by G-CSF in mice. J Exp Med. 2011 Feb 14;208(2):251-60. doi: 10.1084/jem.20101700. Epub 2011 Jan 31.
• DiPersio JF, Stadtmauer EA, Nademanee A, Micallef IN, Stiff PJ, Kaufman JL, Maziarz RT, Hosing C, Früehauf S, Horwitz M, Cooper D, Bridger G, Calandra G; 3102 Investigators. Plerixafor and G-CSF versus placebo and G-CSF to mobilize hematopoietic stem cells for autologous stem cell transplantation in patients with multiple myeloma. Blood. 2009 Jun 4;113(23):5720-6. doi: 10.1182/blood-2008-08-174946. Epub 2009 Apr 10.
• Hicks ML, Lonial S, Langston A, Flowers C, Roback JD, Smith KJ, Mossavi Sai S, Teagarden D, Hamilton ES, Waller EK, Kaufman J. Optimizing the timing of chemotherapy for mobilizing autologous blood hematopoietic progenitor cells. Transfusion. 2007 Apr;47(4):629-35. Erratum in: Transfusion. 2007 May;47(5):952. Kaufman, Jonathan [added].
• Jung Y, Wang J, Schneider A, Sun YX, Koh-Paige AJ, Osman NI, McCauley LK, Taichman RS. Regulation of SDF-1 (CXCL12) production by osteoblasts; a possible mechanism for stem cell homing. Bone. 2006 Apr;38(4):497-508. Epub 2005 Dec 5.
• Kaufman JL, Flowers CR, Rados KD, Calandra GB, Vose JM, Hewes LB, Lonial S, Langston AA, Khoury HJ, Lechowicz MJ, Waller EK. A prospective clinical trial evaluating the safety and efficacy of the combination of rituximab and plerixafor as a mobilization regimen for patients with lymphoma. Transfusion. 2013 Jan;53(1):76-84. doi: 10.1111/j.1537-2995.2012.03719.x. Epub 2012 May 25.
• Koenigsmann M, Jentsch-Ullrich K, Mohren M, Becker E, Heim M, Franke A. The role of diagnosis in patients failing peripheral blood progenitor cell mobilization. Transfusion. 2004 May;44(5):777-84.
• Kumar S, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Gastineau DA, Litzow MR, Fonseca R, Roy V, Rajkumar SV, Gertz MA. Impact of lenalidomide therapy on stem cell mobilization and engraftment post-peripheral blood stem cell transplantation in patients with newly diagnosed myeloma. Leukemia. 2007 Sep;21(9):2035-42. Epub 2007 Jun 21.
• Lazarus HM, Loberiza FR Jr, Zhang MJ, Armitage JO, Ballen KK, Bashey A, Bolwell BJ, Burns LJ, Freytes CO, Gale RP, Gibson J, Herzig RH, LeMaistre CF, Marks D, Mason J, Miller AM, Milone GA, Pavlovsky S, Reece DE, Rizzo JD, van Besien K, Vose JM, Horowitz MM. Autotransplants for Hodgkin's disease in first relapse or second remission: a report from the autologous blood and marrow transplant registry (ABMTR). Bone Marrow Transplant. 2001 Feb;27(4):387-96.
• Lemoli RM, Martinelli G, Zamagni E, Motta MR, Rizzi S, Terragna C, Rondelli R, Ronconi S, Curti A, Bonifazi F, Tura S, Cavo M. Engraftment, clinical, and molecular follow-up of patients with multiple myeloma who were reinfused with highly purified CD34+ cells to support single or tandem high-dose chemotherapy. Blood. 2000 Apr 1;95(7):2234-9.
• Li J, Hamilton E, Vaughn L, Graiser M, Renfroe H, Lechowicz MJ, Langston A, Prichard JM, Anderson D, Gleason C, Lonial S, Flowers CR, Kaufman JL, Waller EK. Effectiveness and cost analysis of "just-in-time" salvage plerixafor administration in autologous transplant patients with poor stem cell mobilization kinetics. Transfusion. 2011 Oct;51(10):2175-82. doi: 10.1111/j.1537-2995.2011.03136.x. Epub 2011 Apr 14.
• Mazumder A, Kaufman J, Niesvizky R, Lonial S, Vesole D, Jagannath S. Effect of lenalidomide therapy on mobilization of peripheral blood stem cells in previously untreated multiple myeloma patients. Leukemia. 2008 Jun;22(6):1280-1; author reply 1281-2. Epub 2007 Nov 22.
• Paripati H, Stewart AK, Cabou S, Dueck A, Zepeda VJ, Pirooz N, Ehlenbeck C, Reeder C, Slack J, Leis JF, Boesiger J, Torloni AS, Fonseca R, Bergsagel PL. Compromised stem cell mobilization following induction therapy with lenalidomide in myeloma. Leukemia. 2008 Jun;22(6):1282-4. doi: 10.1038/sj.leu.2405100. Epub 2008 Jan 24.
• Ponomaryov T, Peled A, Petit I, Taichman RS, Habler L, Sandbank J, Arenzana-Seisdedos F, Magerus A, Caruz A, Fujii N, Nagler A, Lahav M, Szyper-Kravitz M, Zipori D, Lapidot T. Induction of the chemokine stromal-derived factor-1 following DNA damage improves human stem cell function. J Clin Invest. 2000 Dec;106(11):1331-9.
• Siena S, Bregni M, Brando B, Ravagnani F, Bonadonna G, Gianni AM. Circulation of CD34+ hematopoietic stem cells in the peripheral blood of high-dose cyclophosphamide-treated patients: enhancement by intravenous recombinant human granulocyte-macrophage colony-stimulating factor. Blood. 1989 Nov 1;74(6):1905-14.
• Smith TJ, Khatcheressian J, Lyman GH, Ozer H, Armitage JO, Balducci L, Bennett CL, Cantor SB, Crawford J, Cross SJ, Demetri G, Desch CE, Pizzo PA, Schiffer CA, Schwartzberg L, Somerfield MR, Somlo G, Wade JC, Wade JL, Winn RJ, Wozniak AJ, Wolff AC. 2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol. 2006 Jul 1;24(19):3187-205. Epub 2006 May 8.

• Responsible Party: Edmund Waller, MD, Emory University
• ClinicalTrials.gov Identifier: NCT01095757
• Other Study ID Numbers: IRB00027735; WCI1671-09
• First Posted: Mar 30, 2010
• Last Update Posted: Sep 29, 2014
• Last Verified: Sep 1, 2014

• Keywords provided by Edmund Waller, MD, Emory University: Myeloma; Lymphoma; Stem cell transplantation
• Additional relevant MeSH terms: Lymphoma; Plerixafor

Study Results

Participant Flow

Arm/Group Title	Plerixafor + Chemo and G-CSF
Arm/Group Description	Patients who receive a combination of Plerixafor, chemotherapy and granulocyte-colony stimulating factor (G-CSF). Plerixafor : 240 µg/kg subcutaneous injection on the day that the absolute neutrophil count (ANC) is > 1500/mm3 and on each day of apheresis for a total of 4 aphereses or the target cluster of differentiation 34 (CD34) cell dose has been reached.
Period Title: Overall Study
STARTED	45
COMPLETED	45
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Plerixafor + Chemo and G-CSF
Arm/Group Description	Patients who receive a combination of Plerixafor, chemotherapy and G-CSF. Plerixafor : 240 µg/kg subcutaneous injection on the day that the ANC is > 1500/mm3 and on each day of apheresis for a total of 4 aphereses or the target CD34 cell dose has been reached.
Overall Participants	45
Age (years) [Median (Full Range) ]
Multiple Myeloma (MM), n = 17	58
Lymphoma, n = 28	56
Sex: Female, Male (Count of Participants)
Female	15 33.3%
Male	30 66.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	2 4.4%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	14 31.1%
White	29 64.4%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	45 100%

Outcome Measures

1. Primary Outcome

Title	Patients Achieving Greater Than or Equal to 5 x 10^6 of CD34+ Cells/kg in a Single Day of Apheresis
Time Frame	Within the first 4 days following the first dose of Plerixafor

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Multiple Myeloma	Lymphoma
Arm/Group Description	Patients who receive a combination of Plerixafor, chemotherapy and G-CSF. Plerixafor : 240 µg/kg subcutaneous injection on the day that the ANC is > 1500/mm3 and on each day of apheresis for a total of 4 aphereses or the target CD34 cell dose has been reached.	Patients who receive a combination of Plerixafor, chemotherapy and G-CSF. Plerixafor : 240 µg/kg subcutaneous injection on the day that the ANC is > 1500/mm3 and on each day of apheresis for a total of 4 aphereses or the target CD34 cell dose has been reached.
Measure Participants	10	23
Number [participants]	9 20%	17 NaN

2. Secondary Outcome

Title	Average Number of Days for Engraftment (Engraftment Defined as Absolute Neutrophil Count>500)
Time Frame	Within the first 4 days following the first dose of Plerixafor

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Multiple Myeloma	Lymphoma
Arm/Group Description	Patients who receive a combination of Plerixafor, chemotherapy and G-CSF. Plerixafor : 240 µg/kg subcutaneous injection on the day that the ANC is > 1500/mm3 and on each day of apheresis for a total of 4 aphereses or the target CD34 cell dose has been reached.	Patients who receive a combination of Plerixafor, chemotherapy and G-CSF. Plerixafor : 240 µg/kg subcutaneous injection on the day that the ANC is > 1500/mm3 and on each day of apheresis for a total of 4 aphereses or the target CD34 cell dose has been reached.
Measure Participants	10	23
Mean (Standard Deviation) [days]	12.4 (1.62)	12.105 (1.63)

3. Primary Outcome

Title	Patients Achieving >= 3 X 10^6 CD34+ Cell/Kg
Time Frame	Within the first 4 days following the first dose of Plerixafor

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Multiple Myeloma	Lymphoma
Arm/Group Description	Patients who receive a combination of Plerixafor, chemotherapy and G-CSF. Plerixafor : 240 µg/kg subcutaneous injection on the day that the ANC is > 1500/mm3 and on each day of apheresis for a total of 4 aphereses or the target CD34 cell dose has been reached.	Patients who receive a combination of Plerixafor, chemotherapy and G-CSF. Plerixafor : 240 µg/kg subcutaneous injection on the day that the ANC is > 1500/mm3 and on each day of apheresis for a total of 4 aphereses or the target CD34 cell dose has been reached.
Measure Participants	10	23
Number [participants]	10 22.2%	23 NaN

Adverse Events

Arm/Group Title	Plerixafor + Chemo and G-CSF
Arm/Group Description	Patients who receive a combination of Plerixafor, chemotherapy and G-CSF. Plerixafor : 240 µg/kg subcutaneous injection on the day that the ANC is > 1500/mm3 and on each day of apheresis for a total of 4 aphereses or the target CD34 cell dose has been reached.
All Cause Mortality
	Plerixafor + Chemo and G-CSF
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Plerixafor + Chemo and G-CSF
	Affected / at Risk (%)	# Events
Total	0/45 (0%)
Other (Not Including Serious) Adverse Events
	Plerixafor + Chemo and G-CSF
	Affected / at Risk (%)	# Events
Total	29/45 (64.4%)
Blood and lymphatic system disorders
Hypokalemia	8/45 (17.8%)
Thrombocytopenia Grade 1/2	26/45 (57.8%)
Thrombocytopenia Over Grade 2	17/45 (37.8%)
Anemia	1/45 (2.2%)
Gastrointestinal disorders
Nausea	13/45 (28.9%)
Diarrhea	12/45 (26.7%)
General disorders
Fatigue	11/45 (24.4%)
Lightheadedness	7/45 (15.6%)
Headache	6/45 (13.3%)
Musculoskeletal and connective tissue disorders
Bone Pain	12/45 (26.7%)

Limitations/Caveats

[Not Specified]

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.