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Safety of Post-transplant Alpha-beta Depleted T-cell Infusion Following Haploidentical Stem Cell Transplant (Haplo SCT) (ABD)

Primary Purpose

Hematologic Neoplasms, Graft-Versus-Host Disease

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Alpha-beta depleted T-cell infusion after post-transplant cyclophosphamide.
Sponsored by
Ayman Saad
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hematologic Neoplasms focused on measuring stem cell transplant

Eligibility Criteria

19 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Neoplastic hematological disorder with indication of allogeneic transplant
  • No available suitable HLA-matched donor
  • Adequate cardiac, pulmonary, renal, and hepatic function
  • Karnofsky performance status score greater than or equal to 70%

Exclusion Criteria:

  • Medication non-compliance
  • No appropriate caregiver identified
  • Uncontrolled medical or psychiatric disorder
  • Active central nervous system (CNS) neoplastic involvement
  • Known allergy to Dimethyl Sulfoxide
  • HIV1 or HIV2 positive
  • Pregnant or breastfeeding

Sites / Locations

  • UAB Medical Center (University of Alabama at Birmingham)

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Alpha-beta depleted T-cell infusion

Arm Description

Post-transplant alpha-beta depleted T-cell infusion after post-transplant cyclophosphamide.

Outcomes

Primary Outcome Measures

Number of Participants That Experience Acute Haploidentical Alpha Beta Depleted Transplant (aGVHD)
Patients will be monitored for Grade IV aGVHD and organ toxicity. Acute assessment will be done using the modified Keystone (Glucksberg) consensus criteria.
Number of Participants That Experience Chronic Haploidentical Alpha Beta Depleted Transplant (cGVHD)
Patients will be monitored for Grade IV cGVHD and organ toxicity. Chronic assessment will be done using the conventional criteria.

Secondary Outcome Measures

Full Information

First Posted
July 14, 2014
Last Updated
April 11, 2019
Sponsor
Ayman Saad
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1. Study Identification

Unique Protocol Identification Number
NCT02193880
Brief Title
Safety of Post-transplant Alpha-beta Depleted T-cell Infusion Following Haploidentical Stem Cell Transplant (Haplo SCT)
Acronym
ABD
Official Title
Safety of Post-transplant Alpha-beta Depleted T-cell Infusion Following Haploidentical Stem Cell Transplant (Haplo SCT)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2019
Overall Recruitment Status
Completed
Study Start Date
October 9, 2014 (Actual)
Primary Completion Date
March 13, 2018 (Actual)
Study Completion Date
March 13, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Ayman Saad

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Device Product Not Approved or Cleared by U.S. FDA
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to determine the safety and efficacy of post-transplant cyclophosphamide and a post-transplant infusion of donor cells, that have been specially processed to remove alpha beta t-cells, in patients undergoing a haploidentical allogeneic stem cell transplant to help reduce the risk of relapse without increasing the risk of graft-versus-host disease.
Detailed Description
Transplant patients participating in this clinical trial will receive one of 3 standard pre-transplant chemotherapy preparative regimens as appropriate for their specific disease. They will then receive a standard non-manipulated donor stem cell infusion on transplant day (day 0) followed by cyclophosphamide (days +3 and +4) and an alpha-beta t-cell reduced donor stem cell infusion on day +7.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematologic Neoplasms, Graft-Versus-Host Disease
Keywords
stem cell transplant

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
7 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Alpha-beta depleted T-cell infusion
Arm Type
Other
Arm Description
Post-transplant alpha-beta depleted T-cell infusion after post-transplant cyclophosphamide.
Intervention Type
Device
Intervention Name(s)
Alpha-beta depleted T-cell infusion after post-transplant cyclophosphamide.
Intervention Description
Post-transplant alpha-beta depleted T-cell infusion after post-transplant cyclophosphamide.
Primary Outcome Measure Information:
Title
Number of Participants That Experience Acute Haploidentical Alpha Beta Depleted Transplant (aGVHD)
Description
Patients will be monitored for Grade IV aGVHD and organ toxicity. Acute assessment will be done using the modified Keystone (Glucksberg) consensus criteria.
Time Frame
From baseline and before day +100 of transplant.
Title
Number of Participants That Experience Chronic Haploidentical Alpha Beta Depleted Transplant (cGVHD)
Description
Patients will be monitored for Grade IV cGVHD and organ toxicity. Chronic assessment will be done using the conventional criteria.
Time Frame
From baseline and before day +100 of transplant.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Neoplastic hematological disorder with indication of allogeneic transplant No available suitable HLA-matched donor Adequate cardiac, pulmonary, renal, and hepatic function Karnofsky performance status score greater than or equal to 70% Exclusion Criteria: Medication non-compliance No appropriate caregiver identified Uncontrolled medical or psychiatric disorder Active central nervous system (CNS) neoplastic involvement Known allergy to Dimethyl Sulfoxide HIV1 or HIV2 positive Pregnant or breastfeeding
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ayman Saad, MD
Organizational Affiliation
University of Alabama at Birmingham
Official's Role
Principal Investigator
Facility Information:
Facility Name
UAB Medical Center (University of Alabama at Birmingham)
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
17785583
Citation
Lee SJ, Klein J, Haagenson M, Baxter-Lowe LA, Confer DL, Eapen M, Fernandez-Vina M, Flomenberg N, Horowitz M, Hurley CK, Noreen H, Oudshoorn M, Petersdorf E, Setterholm M, Spellman S, Weisdorf D, Williams TM, Anasetti C. High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation. Blood. 2007 Dec 15;110(13):4576-83. doi: 10.1182/blood-2007-06-097386. Epub 2007 Sep 4.
Results Reference
background
PubMed Identifier
22046559
Citation
Alshemmari S, Ameen R, Gaziev J. Haploidentical hematopoietic stem-cell transplantation in adults. Bone Marrow Res. 2011;2011:303487. doi: 10.1155/2011/303487. Epub 2011 Jul 13.
Results Reference
background
PubMed Identifier
16641398
Citation
Copelan EA. Hematopoietic stem-cell transplantation. N Engl J Med. 2006 Apr 27;354(17):1813-26. doi: 10.1056/NEJMra052638. No abstract available.
Results Reference
background
PubMed Identifier
15753458
Citation
Aversa F, Terenzi A, Tabilio A, Falzetti F, Carotti A, Ballanti S, Felicini R, Falcinelli F, Velardi A, Ruggeri L, Aloisi T, Saab JP, Santucci A, Perruccio K, Martelli MP, Mecucci C, Reisner Y, Martelli MF. Full haplotype-mismatched hematopoietic stem-cell transplantation: a phase II study in patients with acute leukemia at high risk of relapse. J Clin Oncol. 2005 May 20;23(15):3447-54. doi: 10.1200/JCO.2005.09.117. Epub 2005 Mar 7.
Results Reference
background
PubMed Identifier
2390646
Citation
Gale RP, Horowitz MM. Graft-versus-leukemia in bone marrow transplantation. The Advisory Committee of the International Bone Marrow Transplant Registry. Bone Marrow Transplant. 1990 Jul;6 Suppl 1:94-7.
Results Reference
background
PubMed Identifier
2297567
Citation
Horowitz MM, Gale RP, Sondel PM, Goldman JM, Kersey J, Kolb HJ, Rimm AA, Ringden O, Rozman C, Speck B, et al. Graft-versus-leukemia reactions after bone marrow transplantation. Blood. 1990 Feb 1;75(3):555-62.
Results Reference
background
PubMed Identifier
16167015
Citation
Ferrara JL, Yanik G. Acute graft versus host disease: pathophysiology, risk factors, and prevention strategies. Clin Adv Hematol Oncol. 2005 May;3(5):415-9, 428.
Results Reference
background
PubMed Identifier
22278184
Citation
Oevermann L, Handgretinger R. New strategies for haploidentical transplantation. Pediatr Res. 2012 Apr;71(4 Pt 2):418-26. doi: 10.1038/pr.2011.60. Epub 2012 Jan 25.
Results Reference
background
PubMed Identifier
15744234
Citation
Lamb LS Jr, Lopez RD. gammadelta T cells: a new frontier for immunotherapy? Biol Blood Marrow Transplant. 2005 Mar;11(3):161-8. doi: 10.1016/j.bbmt.2004.11.015. Erratum In: Biol Blood Marrow Transplant. 2005 Apr;11(4):318.
Results Reference
background
PubMed Identifier
20889923
Citation
Moretta L, Locatelli F, Pende D, Marcenaro E, Mingari MC, Moretta A. Killer Ig-like receptor-mediated control of natural killer cell alloreactivity in haploidentical hematopoietic stem cell transplantation. Blood. 2011 Jan 20;117(3):764-71. doi: 10.1182/blood-2010-08-264085. Epub 2010 Oct 1.
Results Reference
background
PubMed Identifier
23386902
Citation
Palmer JM, Rajasekaran K, Thakar MS, Malarkannan S. Clinical relevance of natural killer cells following hematopoietic stem cell transplantation. J Cancer. 2013;4(1):25-35. doi: 10.7150/jca.5049. Epub 2012 Dec 5.
Results Reference
background
PubMed Identifier
8938522
Citation
Lamb LS Jr, Henslee-Downey PJ, Parrish RS, Godder K, Thompson J, Lee C, Gee AP. Increased frequency of TCR gamma delta + T cells in disease-free survivors following T cell-depleted, partially mismatched, related donor bone marrow transplantation for leukemia. J Hematother. 1996 Oct;5(5):503-9. doi: 10.1089/scd.1.1996.5.503.
Results Reference
background
PubMed Identifier
19746645
Citation
Lamb LS Jr, Gee AP, Hazlett LJ, Musk P, Parrish RS, O'Hanlon TP, Geier SS, Folk RS, Harris WG, McPherson K, Lee C, Henslee-Downey PJ. Influence of T cell depletion method on circulating gammadelta T cell reconstitution and potential role in the graft-versus-leukemia effect. Cytotherapy. 1999;1(1):7-19. doi: 10.1080/0032472031000141295. Erratum In: Cytotherapy. 1999;1(4):360.
Results Reference
background
PubMed Identifier
17450185
Citation
Godder KT, Henslee-Downey PJ, Mehta J, Park BS, Chiang KY, Abhyankar S, Lamb LS. Long term disease-free survival in acute leukemia patients recovering with increased gammadelta T cells after partially mismatched related donor bone marrow transplantation. Bone Marrow Transplant. 2007 Jun;39(12):751-7. doi: 10.1038/sj.bmt.1705650. Epub 2007 Apr 23.
Results Reference
background
PubMed Identifier
23206843
Citation
Handgretinger R. New approaches to graft engineering for haploidentical bone marrow transplantation. Semin Oncol. 2012 Dec;39(6):664-73. doi: 10.1053/j.seminoncol.2012.09.007.
Results Reference
background
PubMed Identifier
1671578
Citation
Eto M, Mayumi H, Tomita Y, Yoshikai Y, Nishimura Y, Maeda T, Ando T, Nomoto K. Specific destruction of host-reactive mature T cells of donor origin prevents graft-versus-host disease in cyclophosphamide-induced tolerant mice. J Immunol. 1991 Mar 1;146(5):1402-9.
Results Reference
background
PubMed Identifier
11985515
Citation
Strauss G, Osen W, Debatin KM. Induction of apoptosis and modulation of activation and effector function in T cells by immunosuppressive drugs. Clin Exp Immunol. 2002 May;128(2):255-66. doi: 10.1046/j.1365-2249.2002.01777.x.
Results Reference
background
PubMed Identifier
11939602
Citation
Luznik L, Engstrom LW, Iannone R, Fuchs EJ. Posttransplantation cyclophosphamide facilitates engraftment of major histocompatibility complex-identical allogeneic marrow in mice conditioned with low-dose total body irradiation. Biol Blood Marrow Transplant. 2002;8(3):131-8. doi: 10.1053/bbmt.2002.v8.pm11939602.
Results Reference
background
PubMed Identifier
11719388
Citation
Luznik L, Jalla S, Engstrom LW, Iannone R, Fuchs EJ. Durable engraftment of major histocompatibility complex-incompatible cells after nonmyeloablative conditioning with fludarabine, low-dose total body irradiation, and posttransplantation cyclophosphamide. Blood. 2001 Dec 1;98(12):3456-64. doi: 10.1182/blood.v98.12.3456.
Results Reference
background
PubMed Identifier
8877390
Citation
Mayumi H, Umesue M, Nomoto K. Cyclophosphamide-induced immunological tolerance: an overview. Immunobiology. 1996 Jul;195(2):129-39. doi: 10.1016/S0171-2985(96)80033-7.
Results Reference
background
PubMed Identifier
18940683
Citation
Burroughs LM, O'Donnell PV, Sandmaier BM, Storer BE, Luznik L, Symons HJ, Jones RJ, Ambinder RF, Maris MB, Blume KG, Niederwieser DW, Bruno B, Maziarz RT, Pulsipher MA, Petersen FB, Storb R, Fuchs EJ, Maloney DG. Comparison of outcomes of HLA-matched related, unrelated, or HLA-haploidentical related hematopoietic cell transplantation following nonmyeloablative conditioning for relapsed or refractory Hodgkin lymphoma. Biol Blood Marrow Transplant. 2008 Nov;14(11):1279-87. doi: 10.1016/j.bbmt.2008.08.014.
Results Reference
background
PubMed Identifier
18489989
Citation
Luznik L, O'Donnell PV, Symons HJ, Chen AR, Leffell MS, Zahurak M, Gooley TA, Piantadosi S, Kaup M, Ambinder RF, Huff CA, Matsui W, Bolanos-Meade J, Borrello I, Powell JD, Harrington E, Warnock S, Flowers M, Brodsky RA, Sandmaier BM, Storb RF, Jones RJ, Fuchs EJ. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2008 Jun;14(6):641-50. doi: 10.1016/j.bbmt.2008.03.005.
Results Reference
background
PubMed Identifier
21527516
Citation
Brunstein CG, Fuchs EJ, Carter SL, Karanes C, Costa LJ, Wu J, Devine SM, Wingard JR, Aljitawi OS, Cutler CS, Jagasia MH, Ballen KK, Eapen M, O'Donnell PV; Blood and Marrow Transplant Clinical Trials Network. Alternative donor transplantation after reduced intensity conditioning: results of parallel phase 2 trials using partially HLA-mismatched related bone marrow or unrelated double umbilical cord blood grafts. Blood. 2011 Jul 14;118(2):282-8. doi: 10.1182/blood-2011-03-344853. Epub 2011 Apr 28.
Results Reference
background
PubMed Identifier
22773801
Citation
Alvarnas JC, Brown PA, Aoun P, Ballen KK, Bellam N, Blum W, Boyer MW, Carraway HE, Coccia PF, Coutre SE, Cultrera J, Damon LE, DeAngelo DJ, Douer D, Frangoul H, Frankfurt O, Goorha S, Millenson MM, O'Brien S, Petersdorf SH, Rao AV, Terezakis S, Uy G, Wetzler M, Zelenetz AD, Naganuma M, Gregory KM; National Comprehensive Cancer Network. Acute lymphoblastic leukemia. J Natl Compr Canc Netw. 2012 Jul 1;10(7):858-914. doi: 10.6004/jnccn.2012.0089.
Results Reference
background
PubMed Identifier
21917626
Citation
Hoppe RT, Advani RH, Ai WZ, Ambinder RF, Bello CM, Bierman PJ, Blum KA, Dabaja B, Duron Y, Forero A, Gordon LI, Hernandez-Ilizaliturri FJ, Hochberg EP, Maloney DG, Mansur D, Mauch PM, Metzger M, Moore JO, Morgan D, Moskowitz CH, Poppe M, Pro B, Weiss L, Winter JN, Yahalom J; NCCN Hodgkin Lymphoma. Hodgkin lymphoma. J Natl Compr Canc Netw. 2011 Sep 1;9(9):1020-58. doi: 10.6004/jnccn.2011.0086. No abstract available.
Results Reference
background
PubMed Identifier
23486452
Citation
Zelenetz AD, Wierda WG, Abramson JS, Advani RH, Andreadis CB, Bartlett N, Bellam N, Byrd JC, Czuczman MS, Fayad LE, Glenn MJ, Gockerman JP, Gordon LI, Harris NL, Hoppe RT, Horwitz SM, Kelsey CR, Kim YH, Krivacic S, LaCasce AS, Nademanee A, Porcu P, Press O, Pro B, Reddy N, Sokol L, Swinnen L, Tsien C, Vose JM, Yahalom J, Zafar N, Dwyer MA, Naganuma M; National Comprehensive Cancer Network. Non-Hodgkin's lymphomas, version 1.2013. J Natl Compr Canc Netw. 2013 Mar 1;11(3):257-72; quiz 273. doi: 10.6004/jnccn.2013.0037.
Results Reference
background
PubMed Identifier
24029121
Citation
O'Donnell MR, Tallman MS, Abboud CN, Altman JK, Appelbaum FR, Arber DA, Attar E, Borate U, Coutre SE, Damon LE, Lancet J, Maness LJ, Marcucci G, Martin MG, Millenson MM, Moore JO, Ravandi F, Shami PJ, Smith BD, Stone RM, Strickland SA, Wang ES, Gregory KM, Naganuma M; National Comprehensive Cancer Network. Acute myeloid leukemia, version 2.2013. J Natl Compr Canc Netw. 2013 Sep 1;11(9):1047-55. doi: 10.6004/jnccn.2013.0127.
Results Reference
background
PubMed Identifier
24225967
Citation
O'Brien S, Radich JP, Abboud CN, Akhtari M, Altman JK, Berman E, DeAngelo DJ, Deininger M, Devine S, Fathi AT, Gotlib J, Jagasia M, Kropf P, Moore JO, Pallera A, Pinilla-Ibarz J, Reddy VV, Shah NP, Smith BD, Snyder DS, Wetzler M, Gregory K, Sundar H; Ntational comprehensive cancer network. Chronic Myelogenous Leukemia, Version 1.2014. J Natl Compr Canc Netw. 2013 Nov;11(11):1327-40. doi: 10.6004/jnccn.2013.0157.
Results Reference
background
PubMed Identifier
23847220
Citation
Greenberg PL, Attar E, Bennett JM, Bloomfield CD, Borate U, De Castro CM, Deeg HJ, Frankfurt O, Gaensler K, Garcia-Manero G, Gore SD, Head D, Komrokji R, Maness LJ, Millenson M, O'Donnell MR, Shami PJ, Stein BL, Stone RM, Thompson JE, Westervelt P, Wheeler B, Shead DA, Naganuma M. Myelodysplastic syndromes: clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2013 Jul;11(7):838-74. doi: 10.6004/jnccn.2013.0104.
Results Reference
background
PubMed Identifier
23349007
Citation
Tefferi A. Primary myelofibrosis: 2013 update on diagnosis, risk-stratification, and management. Am J Hematol. 2013 Feb;88(2):141-50. doi: 10.1002/ajh.23384. Erratum In: Am J Hematol. 2013 May;88(5):437-45.
Results Reference
background
PubMed Identifier
7581076
Citation
Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, Thomas ED. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995 Jun;15(6):825-8.
Results Reference
background
PubMed Identifier
19436029
Citation
Le Tourneau C, Lee JJ, Siu LL. Dose escalation methods in phase I cancer clinical trials. J Natl Cancer Inst. 2009 May 20;101(10):708-20. doi: 10.1093/jnci/djp079. Epub 2009 May 12.
Results Reference
background
PubMed Identifier
20124511
Citation
Luznik L, Bolanos-Meade J, Zahurak M, Chen AR, Smith BD, Brodsky R, Huff CA, Borrello I, Matsui W, Powell JD, Kasamon Y, Goodman SN, Hess A, Levitsky HI, Ambinder RF, Jones RJ, Fuchs EJ. High-dose cyclophosphamide as single-agent, short-course prophylaxis of graft-versus-host disease. Blood. 2010 Apr 22;115(16):3224-30. doi: 10.1182/blood-2009-11-251595. Epub 2010 Feb 2.
Results Reference
background
Citation
Kaplan, EL, Meier, P. Nonparametric estimation from incomplete observations. Journal of the American Statistical Association 53(282): 457-481, 1958.
Results Reference
background
Citation
Gray, RJ. A class of K-sample tests for comparing the cumulative incidence of a competing risk. The Annals of Statistics, 1141-1154, 1988.
Results Reference
background
Links:
URL
http://www.uab.edu/medicine/bonemarrow/
Description
Click here for more information about the Bone Marrow Transplantation and Cell Therapy Program at the University of Alabama at Birmingham.

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Safety of Post-transplant Alpha-beta Depleted T-cell Infusion Following Haploidentical Stem Cell Transplant (Haplo SCT)

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