Acute Lymphoblastic LeukemiaPhase 1/2NCT01810120
Trial to Assess the Efficacy of a TCR Alfa Beta Depleted Graft in Pediatric Affected by ALL or AML and Receiving an HSCT
A Phase 1/2 study testing TCR alfa beta T cell depletion in people with Acute Lymphoblastic Leukemia and Leukemia Acute Myeloid - AML, run by Mariella Enoc at 1 site in Italy.
Trial 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… Read more about this study
- Who is it for?
- Ages 3 months to 20 years
- Conditions the study is for
- Acute Lymphoblastic Leukemia, Leukemia Acute Myeloid - AML, Non-Hodgkin Lymphoma
- What is being tested?
- TCR alfa beta T cell depletion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteItaly
- Study dates
- Jan 2012to Dec 2016
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 months to 20 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- Grade >II acute GvHD or chronic extensive GvHD at the time of inclusion
- Patient receiving an immunosuppressive treatment for GvHD treatment at the time of inclusion
- 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.
Trial locations and contacts
1 site in 1 country.
Italy1 site
Department of Oncology/Hematology of the Hospital Bambino Gesù (Roma)
Rome, Italy, 00165
About this study
Official title: Phase I/II Study of Allogeneic Hematopoietic Stem Cell Transplantation From an HLA-partially Matched Family Donor After TCR Alfa Beta Negative Selection in Pediatric Patients Affected by Hematological Disorders
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.
Read the detailed description
In this study the hypothesis is that the transplantation of Peripheral blood stem cells (PBSC)selectively depleted of TCR alfa beta T lymphocytes would offers some advantages over the use of positively selected CD34+ stem cells because of the presence of other non-stem ancillary cells (in particular Natural killer (NK) and alfa beta T cells) that might have potential positive effects on the outcome of the transplant.
The clinical relevance of NK-cell alloreactivity has been demonstrated in adult patients affected by Acute myeloid leukemia (AML) and given T-cell depleted HSCT from an HLA-disparate relative where a subgroup of patients had a particularly low risk of leukemia relapse. These patients belonged to the group transplanted from a donor having NK cells that were alloreactive towards recipient targets i.e. the patient cells express HLA-class I alleles that do not share the inhibiting allelic determinants recognized by Killer immunoglobulin-like receptors (KIR) on donor NK cells. The emergence of this concept of NK-cell alloreactivity has represented a sort of revolution in the field of Haplo-identical hematopoietic stem cell translantation (haplo-HSCT), as the presence of alloreactive NK cells has been shown to positively affect the outcome of transplantation in adults and to display a Graft versus leukemia (GvL) effect that can compensate for the lack of T-specific anti-tumor effect.
The purpose of this study is to evaluate the feasibility and safety of the selective infusion of TCR alfa beta T cell depleted graft in pediatric patients affected by malignant or non malignant hematological disorders and receiving an HSCT from a partially matched family donor.
This study will provide new data on the feasibility and the safety of using a TCR alfa beta T cell depleted graft instead of fully T cell depleted graft to improve the outcome of patients receiving a haplo-HSCT for the treatment of hematological disorders.
- Conditions
- Acute Lymphoblastic Leukemia, Leukemia Acute Myeloid - AML, Non-Hodgkin Lymphoma, Myelodysplastic Syndromes
- Being tested
- TCR alfa beta T cell depletion
- Keywords
- Hematologic, Malignant, Non-Malignant, Allogeneic, Transplant, Non-Hodgkin Lymphoma, Pediatric, Acute lymphoblastic leukemia, Acute Myeloid leukemia, Myelodysplastic Syndromes, T cells receptor alfa beta
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Lymphoma, Non-Hodgkin, Myelodysplastic Syndromes, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TCR alfa beta T cell depletionBiological
Also called nucleated cells
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
| Study group | Role | What they receive |
|---|---|---|
| TCR alfa beta depleted graft, infusion | Experimental | The leukapheresis product will undergo TCR alfa beta negative selection following the standardized protocol. Receives: Biological: TCR alfa beta T cell depletion |
What is being measured
The primary outcome is the main question the study is designed to answer.
CD34+ cells
Target number of CD34+ cells in at least 80% of the patients
Measured: up to 3 month
Secondary outcomes (4)
Primary and secondary graft failure
Cumulative incidence of primary and secondary graft failure
Measured: up to 24 months after transplantation
Acute and chronic GvHD
Cumulative incidence and severity of acute and chronic GvHD occurring after the transplantation
Measured: up to 24 months after transplantation
Overall survival (OS) and disease-free survival
The overall survival (OS) and disease-free survival probability compared with a cohort of historical controls
Measured: up to 24 months after transplantation
TCR alfa beta cells
The immunological reconstitution of TCR alfa beta cells compared with a cohort of historical controls
Measured: up to 12 months after the transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2013 (estimated)
- Study startJan 2012
- Primary completionSep 2016
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (29)Papers the sponsor has linked to this study.
- Other trials for Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mariella Enoc
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Mariella Enoc, Bambino Gesù Hospital and Research Institute
- Investigators
- Franco Locatelli, Prof, Principal investigator, Bambino Gesù Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01810120
- Sponsor's protocol ID
- OPBG_359.11
- Status last verified
- Jan 2017
- First submitted
- 17 Jan 2012
- Last updated
- 23 Jan 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Copelan EA. Hematopoietic stem-cell transplantation. N Engl J Med. 2006 Apr 27;354(17):1813-26. doi: 10.1056/NEJMra052638. No abstract available.
PubMed 16641398Rocha V, Locatelli F. Searching for alternative hematopoietic stem cell donors for pediatric patients. Bone Marrow Transplant. 2008 Jan;41(2):207-14. doi: 10.1038/sj.bmt.1705963. Epub 2007 Dec 17.
PubMed 18084331Gluckman E. Cord blood transplantation. Biol Blood Marrow Transplant. 2006 Aug;12(8):808-12. doi: 10.1016/j.bbmt.2006.05.011. No abstract available.
PubMed 16864050Locatelli 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.
PubMed 19481979Martelli MF, Aversa F, Bachar-Lustig E, Velardi A, Reich-Zelicher S, Tabilio A, Gur H, Reisner Y. Transplants across human leukocyte antigen barriers. Semin Hematol. 2002 Jan;39(1):48-56. doi: 10.1053/shem.2002.29255.
PubMed 11799529Reisner Y, Kapoor N, Kirkpatrick D, Pollack MS, Cunningham-Rundles S, Dupont B, Hodes MZ, Good RA, O'Reilly RJ. Transplantation for severe combined immunodeficiency with HLA-A,B,D,DR incompatible parental marrow cells fractionated by soybean agglutinin and sheep red blood cells. Blood. 1983 Feb;61(2):341-8.
PubMed 6217853Antoine C, Muller S, Cant A, Cavazzana-Calvo M, Veys P, Vossen J, Fasth A, Heilmann C, Wulffraat N, Seger R, Blanche S, Friedrich W, Abinun M, Davies G, Bredius R, Schulz A, Landais P, Fischer A; European Group for Blood and Marrow Transplantation; European Society for Immunodeficiency. Long-term survival and transplantation of haemopoietic stem cells for immunodeficiencies: report of the European experience 1968-99. Lancet. 2003 Feb 15;361(9357):553-60. doi: 10.1016/s0140-6736(03)12513-5.
PubMed 12598139Bachar-Lustig E, Rachamim N, Li HW, Lan F, Reisner Y. Megadose of T cell-depleted bone marrow overcomes MHC barriers in sublethally irradiated mice. Nat Med. 1995 Dec;1(12):1268-73. doi: 10.1038/nm1295-1268.
PubMed 7489407Reisner Y, Martelli MF. Stem cell escalation enables HLA-disparate haematopoietic transplants in leukaemia patients. Immunol Today. 1999 Aug;20(8):343-7. doi: 10.1016/s0167-5699(98)01428-5.
PubMed 10431152Aversa 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.
PubMed 7524753Aversa 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.
PubMed 9780338Aversa 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.
PubMed 15753458Ciceri 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.
PubMed 18606875Klingebiel 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.
PubMed 20040760Trinchieri G. Biology of natural killer cells. Adv Immunol. 1989;47:187-376. doi: 10.1016/s0065-2776(08)60664-1.
PubMed 2683611