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

• ClinicalTrials.gov Identifier: NCT01095757
• Recruitment Status: Completed
• First Posted: March 30, 2010
• Results First Posted: September 12, 2014
• Last Update Posted: September 29, 2014
• Sponsor: Emory University
• Collaborator: Genzyme, a Sanofi Company
• Information provided by (Responsible Party): Edmund Waller, Emory University

Tracking Information

• First Submitted Date: March 26, 2010
• First Posted Date: March 30, 2010
• Results First Submitted Date: October 22, 2013
• Results First Posted Date: September 12, 2014
• Last Update Posted Date: September 29, 2014
• Study Start Date: March 2010
• Actual Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 5, 2014)

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

• Original Primary Outcome Measures (submitted: March 29, 2010): Proportion of patients achieving the target number of either 5 x 106 (lymphoma) or 10 x 106 (myeloma) of CD34+ cells/kg in a single day of apheresis [ Time Frame: Within the first 4 days following the first dose of Plerixafor ]
• Current Secondary Outcome Measures (submitted: September 5, 2014): 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 ]
• Original Secondary Outcome Measures (submitted: March 29, 2010): Total numbers of CD34+ cells/kg collected, mean numbers of days of apheresis needed to collect the target numbers of CD34+ cells/kg , neutrophil and platelet engraftment and graft durability at 12 months post transplant [ Time Frame: Within the first 4 days following the first dose of Plerixafor ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Evaluation of the Drug Plerixafor in Combination With Chemotherapy and G-CSF for Stem Cell Collection
• Official Title: Evaluation of Plerixafor (Mozobil ™, AMD3100) in Combination With Chemotherapy and G-CSF for CD34+ Cell Mobilization

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Myeloma
• Lymphoma

Intervention

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

Study Arms

Plerixafor + Chemo and G-CSF

Patients who receive a combination of Plerixafor, chemotherapy and G-CSF.

Intervention: Drug: Plerixafor

Publications *

• 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.
• 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.
• 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.
• 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.
• 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.
• 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].
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 16, 2014): 45
• Original Estimated Enrollment (submitted: March 29, 2010): 40
• Actual Study Completion Date: February 2014
• Actual Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01095757
• Other Study ID Numbers: IRB00027735; WCI1671-09 ( Other Identifier: Other )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Edmund Waller, Emory University
• Study Sponsor: Emory University
• Collaborators: Genzyme, a Sanofi Company

Investigators

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

• PRS Account: Emory University
• Verification Date: September 2014