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

NCT01095757 | Completed Phase 2 Results DMC

• 2 other identifiers: IRB00027735WCI1671-09
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

Myeloma; Lymphoma

Keywords

Myeloma; Lymphoma; Stem cell transplantation

Outcome Measures

Primary Outcomes (2)

• 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

• Patients Achieving >= 3 X 10^6 CD34+ Cell/Kg

  Within the first 4 days following the first dose of Plerixafor

Secondary Outcomes (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

Study Arms (1)

Plerixafor + Chemo and G-CSF

OTHER

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

Drug: Plerixafor

Interventions

Plerixafor DRUG

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.

Also known as: Mozobil, AMD3100

Plerixafor + Chemo and G-CSF

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-70 years
• Multiple myeloma (MM) or non-Hodgkin's lymphoma (NHL) patients in first or second complete or partial remission
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Up to 3 prior treatment regimens
• Meet all eligibility requirements for autologous transplant
• Adequate marrow function defined as white blood cells (WBC) \>3,000; ANC \>1,500/mm3; platelets \>75,000/mm3
• Adequate renal function defined as creatinine clearance \> 30 mL/min by Cockcroft-Gault
• Adequate liver function defined as aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/bilirubin \< 2 times upper limit of normal
• Able to provide informed consent
• Women not pregnant and agree to use contraception

You may not qualify if:

• High risk co-morbidities for acute treatment complications (e.g., symptomatic coronary artery disease)
• Brain metastases or carcinomatous meningitis
• Previous treatment with high dose chemotherapy and autologous transplant
• Previous attempt to collect B-hematopoietic progenitor cells (HPCs) following mobilization with growth factors alone, growth factors and chemotherapy, or plerixafor and growth factors
• Acute infection or unexplained fever \>38°C
• Weight \> 175% of ideal body weight as defined by the Devine equation
• Experimental therapy within 4 weeks
• Cytokine administration in the previous 14 days

Sponsors & Collaborators

• Emory University: lead
• Genzyme, a Sanofi Company: collaborator

Study Sites (1)

Emory University Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Related Publications (16)

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  PMID: 11313668 BACKGROUND

• 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.

  PMID: 10733490 BACKGROUND

• 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. doi: 10.1200/JCO.2006.06.4451. Epub 2006 May 8.

  PMID: 16682719 BACKGROUND

• 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.

  PMID: 2478216 BACKGROUND

• 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. doi: 10.1038/sj.bmt.1703082.

  PMID: 11498739 BACKGROUND

• 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. doi: 10.1111/j.0041-1132.2004.03321.x.

  PMID: 15104662 BACKGROUND

• 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. doi: 10.1111/j.1537-2995.2007.01164.x.

  PMID: 17381621 BACKGROUND

• 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.

  PMID: 21492180 BACKGROUND

• 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. doi: 10.1038/sj.leu.2404801. Epub 2007 Jun 21.

  PMID: 17581613 BACKGROUND

• 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. doi: 10.1038/sj.leu.2405035. Epub 2007 Nov 22. No abstract available.

  PMID: 18033320 BACKGROUND

• 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. No abstract available.

  PMID: 18216870 BACKGROUND

• 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.

  PMID: 21282380 BACKGROUND

• 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. doi: 10.1172/JCI10329.

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• 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. doi: 10.1016/j.bone.2005.10.003. Epub 2005 Dec 5.

  PMID: 16337237 BACKGROUND

• DiPersio JF, Stadtmauer EA, Nademanee A, Micallef IN, Stiff PJ, Kaufman JL, Maziarz RT, Hosing C, Fruehauf 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.

  PMID: 19363221 BACKGROUND

• 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.

  PMID: 22624594 BACKGROUND

MeSH Terms

Conditions

Neoplasms, Plasma Cell; Lymphoma

Interventions

plerixafor

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Dr. Edmund Waller
• Organization: Winship Cancer Institute Emory University

ewaller@emory.edu

404-727-4995

Study Officials

• Edmund Waller, MD, PhD

  Emory University Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: March 26, 2010
• First Posted: March 30, 2010
• Study Start: March 1, 2010
• Primary Completion: May 1, 2012
• Study Completion: February 1, 2014
• Last Updated: September 29, 2014
• Results First Posted: September 12, 2014

Record last verified: 2014-09

Locations

US (1)