Trial to Assess the Efficacy of a TCR Alfa Beta Depleted Graft in Pediatric Affected by ALL or AML and Receiving an HSCT

NCT01810120 | Completed Phase 1

• 1 other identifier: OPBG_359.11
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Allocation: Non-Randomized Endpoint Classification: Safety/Feasibility Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment Study to assess the feasibility and safety of the infusion of a T cells receptor (TCR) alfa beta depleted graft in pediatric patients affected by malignant and non-malignant hematological disorders and receiving an Hematopoietic stem cell transplantation (HSCT) from a Human leukocyte antigen (HLA) partially matched family donor.

Conditions

Acute Lymphoblastic Leukemia; Leukemia Acute Myeloid - AML; Non-Hodgkin Lymphoma; Myelodysplastic Syndromes

Keywords

Hematologic; Malignant; Non-Malignant; Allogeneic; Transplant; Non-Hodgkin Lymphoma; Pediatric; Acute lymphoblastic leukemia; Acute Myeloid leukemia; Myelodysplastic Syndromes; T cells receptor alfa beta

Outcome Measures

Primary Outcomes (1)

• CD34+ cells

  Target number of CD34+ cells in at least 80% of the patients

  up to 3 month

Secondary Outcomes (4)

• Primary and secondary graft failure

  up to 24 months after transplantation

• Acute and chronic GvHD

  up to 24 months after transplantation

• Overall survival (OS) and disease-free survival

  up to 24 months after transplantation

• TCR alfa beta cells

  up to 12 months after the transplantation

Study Arms (1)

TCR alfa beta depleted graft, infusion

EXPERIMENTAL

The leukapheresis product will undergo TCR alfa beta negative selection following the standardized protocol.

Biological: TCR alfa beta T cell depletion

Interventions

TCR alfa beta T cell depletion BIOLOGICAL

total nucleated cells from the leukapheresis product will undergo TCR alfa beta negative selection and the product of the depletion will be infused to the patient

Also known as: nucleated cells

TCR alfa beta depleted graft, infusion

Eligibility Criteria

• Age: 3 Months - 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients aged ≥ 3 months and \< 21 years
• Patients diagnosed with malignant hemopathies (Acute Lymphoblastic leukemia (ALL), Acute Myeloid Leukemia (AML), Non-Hodgkin Lymphoma (NHL)) in complete morphological remission or Myelodysplastic Syndromes (MDS), Solid Tumors or non malignant hematological disorders (SCID, Acquired and Congenital Aplastic Anemia, other Primary Immunodeficiencies, Life-threatening Cytopenia) eligible for an allogeneic transplantation and lacking a related or unrelated HLA-matched donor
• Patients displaying an HLA-partially matched family donor
• Lansky/Karnofsky score \> 40, WHO \> 4
• Signed written informed consent

You may not qualify if:

• Dysfunction of liver (ALT/AST \> 5 times normal value, or bilirubin \> 3 times normal value), or of renal function (creatinine clearance \< 30 ml / min)
• Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or left ventricular ejection fraction \<40%)
• Current active infectious disease (including positive HIV serology or viral RNA)
• Serious concurrent uncontrolled medical disorder
• Pregnant or breast feeding female patient
• Lack of parents' informed consent.

Sponsors & Collaborators

• Mariella Enoc: lead

Study Sites (1)

Department of Oncology/Hematology of the Hospital Bambino Gesù (Roma)

Rome, Italy, 00165, Italy

Location

Related Publications (29)

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• Locatelli F, Pende D, Maccario R, Mingari MC, Moretta A, Moretta L. Haploidentical hemopoietic stem cell transplantation for the treatment of high-risk leukemias: how NK cells make the difference. Clin Immunol. 2009 Nov;133(2):171-8. doi: 10.1016/j.clim.2009.04.009. Epub 2009 May 29.

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• Aversa F, Tabilio A, Terenzi A, Velardi A, Falzetti F, Giannoni C, Iacucci R, Zei T, Martelli MP, Gambelunghe C, et al. Successful engraftment of T-cell-depleted haploidentical "three-loci" incompatible transplants in leukemia patients by addition of recombinant human granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells to bone marrow inoculum. Blood. 1994 Dec 1;84(11):3948-55.

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• Aversa F, Tabilio A, Velardi A, Cunningham I, Terenzi A, Falzetti F, Ruggeri L, Barbabietola G, Aristei C, Latini P, Reisner Y, Martelli MF. Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype. N Engl J Med. 1998 Oct 22;339(17):1186-93. doi: 10.1056/NEJM199810223391702.

  PMID: 9780338 BACKGROUND

• 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.

  PMID: 15753458 BACKGROUND

• Ciceri F, Labopin M, Aversa F, Rowe JM, Bunjes D, Lewalle P, Nagler A, Di Bartolomeo P, Lacerda JF, Lupo Stanghellini MT, Polge E, Frassoni F, Martelli MF, Rocha V; Acute Leukemia Working Party (ALWP) of European Blood and Marrow Transplant (EBMT) Group. A survey of fully haploidentical hematopoietic stem cell transplantation in adults with high-risk acute leukemia: a risk factor analysis of outcomes for patients in remission at transplantation. Blood. 2008 Nov 1;112(9):3574-81. doi: 10.1182/blood-2008-02-140095. Epub 2008 Jul 7.

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• Klingebiel T, Cornish J, Labopin M, Locatelli F, Darbyshire P, Handgretinger R, Balduzzi A, Owoc-Lempach J, Fagioli F, Or R, Peters C, Aversa F, Polge E, Dini G, Rocha V; Pediatric Diseases and Acute Leukemia Working Parties of the European Group for Blood and Marrow Transplantation (EBMT). Results and factors influencing outcome after fully haploidentical hematopoietic stem cell transplantation in children with very high-risk acute lymphoblastic leukemia: impact of center size: an analysis on behalf of the Acute Leukemia and Pediatric Disease Working Parties of the European Blood and Marrow Transplant group. Blood. 2010 Apr 29;115(17):3437-46. doi: 10.1182/blood-2009-03-207001. Epub 2009 Dec 29.

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• Moretta A, Locatelli F, Moretta L. Human NK cells: from HLA class I-specific killer Ig-like receptors to the therapy of acute leukemias. Immunol Rev. 2008 Aug;224:58-69. doi: 10.1111/j.1600-065X.2008.00651.x.

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• Merli P, Algeri M, Galaverna F, Bertaina V, Lucarelli B, Boccieri E, Becilli M, Quagliarella F, Rosignoli C, Biagini S, Girolami E, Meschini A, Del Principe G, Sborgia R, Catanoso ML, Carta R, Strocchio L, Pinto RM, Buldini B, Falco M, Meazza R, Pende D, Andreani M, Li Pira G, Pagliara D, Locatelli F. TCRalphabeta/CD19 cell-depleted HLA-haploidentical transplantation to treat pediatric acute leukemia: updated final analysis. Blood. 2024 Jan 18;143(3):279-289. doi: 10.1182/blood.2023021336.

  PMID: 37738655 DERIVED

• Merli P, Pagliara D, Galaverna F, Li Pira G, Andreani M, Leone G, Amodio D, Pinto RM, Bertaina A, Bertaina V, Mastronuzzi A, Strocchio L, Boccieri E, Pende D, Falco M, Di Nardo M, Del Bufalo F, Algeri M, Locatelli F. TCRalphabeta/CD19 depleted HSCT from an HLA-haploidentical relative to treat children with different nonmalignant disorders. Blood Adv. 2022 Jan 11;6(1):281-292. doi: 10.1182/bloodadvances.2021005628.

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• Strocchio L, Pagliara D, Algeri M, Li Pira G, Rossi F, Bertaina V, Leone G, Pinto RM, Andreani M, Agolini E, Girardi K, Gaspari S, Grapulin L, Del Bufalo F, Novelli A, Merli P, Locatelli F. HLA-haploidentical TCRalphabeta+/CD19+-depleted stem cell transplantation in children and young adults with Fanconi anemia. Blood Adv. 2021 Mar 9;5(5):1333-1339. doi: 10.1182/bloodadvances.2020003707.

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• Locatelli F, Merli P, Pagliara D, Li Pira G, Falco M, Pende D, Rondelli R, Lucarelli B, Brescia LP, Masetti R, Milano GM, Bertaina V, Algeri M, Pinto RM, Strocchio L, Meazza R, Grapulin L, Handgretinger R, Moretta A, Bertaina A, Moretta L. Outcome of children with acute leukemia given HLA-haploidentical HSCT after alphabeta T-cell and B-cell depletion. Blood. 2017 Aug 3;130(5):677-685. doi: 10.1182/blood-2017-04-779769. Epub 2017 Jun 6.

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• Airoldi I, Bertaina A, Prigione I, Zorzoli A, Pagliara D, Cocco C, Meazza R, Loiacono F, Lucarelli B, Bernardo ME, Barbarito G, Pende D, Moretta A, Pistoia V, Moretta L, Locatelli F. gammadelta T-cell reconstitution after HLA-haploidentical hematopoietic transplantation depleted of TCR-alphabeta+/CD19+ lymphocytes. Blood. 2015 Apr 9;125(15):2349-58. doi: 10.1182/blood-2014-09-599423. Epub 2015 Jan 22.

  PMID: 25612623 DERIVED

• Bertaina A, Merli P, Rutella S, Pagliara D, Bernardo ME, Masetti R, Pende D, Falco M, Handgretinger R, Moretta F, Lucarelli B, Brescia LP, Li Pira G, Testi M, Cancrini C, Kabbara N, Carsetti R, Finocchi A, Moretta A, Moretta L, Locatelli F. HLA-haploidentical stem cell transplantation after removal of alphabeta+ T and B cells in children with nonmalignant disorders. Blood. 2014 Jul 31;124(5):822-6. doi: 10.1182/blood-2014-03-563817. Epub 2014 May 28.

  PMID: 24869942 DERIVED

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Non-Hodgkin; Myelodysplastic Syndromes; Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma; Bone Marrow Diseases; Leukemia, Myeloid

Study Officials

• Franco Locatelli, Prof

  Bambino Gesù Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director Department of Pediatric Hematology and Oncology

Study Record Dates

• First Submitted: January 17, 2012
• First Posted: March 13, 2013
• Study Start: January 1, 2012
• Primary Completion: September 1, 2016
• Study Completion: December 1, 2016
• Last Updated: January 23, 2017

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)