Leukemia Clinical Trial
Official title:
Allogeneic Haematopoietic Stem Cell Transplantation From a Matched Donor in Patients With Chronic Myeloid Leukemia Failing to Gain Normal Hemopoiesis Under TKIs Therapy
NCT number | NCT02638467 |
Other study ID # | alloCML |
Secondary ID | |
Status | Completed |
Phase | Phase 2 |
First received | |
Last updated | |
Start date | November 2015 |
Est. completion date | February 2020 |
Verified date | November 2020 |
Source | University of Milano Bicocca |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Patients newly diagnosed with chronic phase chronic myeloid leukemia undergo treatment with TK inhibitors (TKI). A possible cause of TK failure is represented by the insufficient recovery of normal Ph- hematopoiesis during TKI treatment, with consequent severe cytopenias that limit TKI adequate administration. Although rare, this event happens in a proportion of 4-5% of CML patients. Our hypothesis is to circumvent this peculiar condition by providing a normal hematopoiesis from a HLA-matched donor (Human Leukocyte Antigen). The transplant procedure is therefore intended in providing a sustained hematopoiesis that will allow an early treatment with an adequate dosing of TKI. The transplant procedure planned in our study is built on all available evidences to provide the lowest incidence of acute and chronic GvHD (Graft-versus-host disease). Therefore, a bone marrow will be the preferential source and a GvHD prophylaxis based on Anti-thrombocyte globulin (ATG) and Cyclosporine/Methotrexate will be used according to standard current experience in the field of family and unrelated donors. The pre-transplant TKI will be continued until aplasia will develop, in order to decrease the tumor load as much as possible.The use of TKIs shortly after transplant carries the risk of inhibiting the newly transplanted hematopoietic cells, as Kit, an important kinase in normal bone marrow cells, is frequently blocked by Abl inhibitors. The use of bosutinib as post-transplant therapy is justified by the lack of Kit inhibition that distinguishes bosutinib from all other TKIs, and which could allow a minimal inhibitory activity against the transplanted normal bone marrow.
Status | Completed |
Enrollment | 2 |
Est. completion date | February 2020 |
Est. primary completion date | November 29, 2018 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 70 Years |
Eligibility | Inclusion Criteria: 1. Chronic Myeloid Leukaemia -CML- in chronic phase (CP) 2. Failure to achieve at least a Major Cytogenetic Response (MCyR) after a minimum of 18 months of TKIs treatment 3. Inability to tolerate 3 months of uninterrupted full dose TKIs therapy due to hematological toxicity 4. A minimum of three treatment interruptions due to hematological toxicity Availability of a HLA-identical related donor (Matched Related Donor, MRD) 5. Availability of unrelated donor (Matched Unrelated Donor, MUD) satisfying the criteria of a 10/10 antigen match at (Human Leukocyte Antigen) HLA-A, -B, -C and - DRB1, -DQB1 at high resolution typing, or 9/10 with a permissive - DP disparity according to Fleischhauer model (Crocchiolo et al, Blood 2009) 6. Target graft size (bone marrow): 7. bone marrow: > 3 x 106 CD34+ cells/kg BW recipient or > 3 x 108 nucleated cells/kg BW 8. Karnofsky Index > 80 % 9. Age =18 and =70 years 10. Adequate contraception in female patients of child-bearing potential 11. Written informed consent Exclusion Criteria: 1. Secondary malignancies 2. A hematopoietic cell transplantation-specific comorbidity index (Sorror et al Appendix C) > 4 3. Known and manifested malignant involvement of the Central Nervous System (CNS) 4. Active infectious disease 5. Active human immunodeficiency virus (HIV), Hepatitis B virus (HBV) or Hepatitis B virus (HCV) infection 6. Impaired liver function (Bilirubin > upper normal limit; Transaminases > 3.0 x upper normal limit) 7. Impaired renal function (Creatinine-clearance < 60 ml/min; Serum Creatinine > 1.5 x upper normal limit). 8. Pleural effusion or ascites > 1.0 L 9. Pregnancy or lactation 10. Known hypersensitivity to Busilvex and/or fludarabine 11 Non-co-operative behaviour or non-compliance 12 Psychiatric diseases or conditions that might impair the ability to give informed consent |
Country | Name | City | State |
---|---|---|---|
Italy | Ospedale San Raffaele | Milano | MI |
Italy | ASST-Monza | Monza | Italy/MB |
Lead Sponsor | Collaborator |
---|---|
University of Milano Bicocca | IRCCS San Raffaele |
Italy,
Heisterkamp N, Stephenson JR, Groffen J, Hansen PF, de Klein A, Bartram CR, Grosveld G. Localization of the c-ab1 oncogene adjacent to a translocation break point in chronic myelocytic leukaemia. Nature. 1983 Nov 17-23;306(5940):239-42. — View Citation
Redaelli A, Bell C, Casagrande J, Stephens J, Botteman M, Laskin B, Pashos C. Clinical and epidemiologic burden of chronic myelogenous leukemia. Expert Rev Anticancer Ther. 2004 Feb;4(1):85-96. Review. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Efficacy as assessed by the percentage of patients with Complete Cytogenetic Response (CCyR) | The percentage of patients with Complete Cytogenetic Response (CCyR) will be calculated as the complement to the percentage of failures on the total number of patients treated, where failure includes the following events: no engraftment, death within 12 months, no CCyR at 12 months. | 12 months | |
Secondary | Overall Survival | 12 months | ||
Secondary | Percentage of patients with engraftment | 12 months | ||
Secondary | percentage of patients with complete chimerism (95%) | Day +28, +56 and +100 | ||
Secondary | Evaluation of Major Cytogenetic Response (MCyR) | Major Cytogenetic Response (MCyR) is < 36% Ph+ metaphases | 12 months | |
Secondary | Evaluation of molecular responses | Molecular response is defined
Complete: if there is undetectable BCR-ABL transcript Major: if ratio BCR/ABL <= 0.1% on International Scale |
12 months | |
Secondary | Relapse incidence (RI) | 12 months | ||
Secondary | Incidence of non-relapse mortality (NRM) | Within day +28 and +360 | ||
Secondary | Incidence and severity of acute and chronic graft vs. host disease (GvHD) | 12 months | ||
Secondary | Quality of Life (QoL) | Evaluation of QoL with EQ-5D-5L (Italian - Version 2) and FACT-Leu (Italian -Version 4) | 12 months | |
Secondary | Overall Survival (OS) | 2 years after transplantation of the last patient included (this is intended to allow evaluations of all expected major molecular responses) | 36 months | |
Secondary | Progression Free Survival (PFS) | 2 years after transplantation of the last patient included (this is intended to allow evaluations of all expected major molecular responses) | 36 months | |
Secondary | Relapse Incidence (RI) | 2 years after transplantation of the last patient included (this is intended to allow evaluations of all expected major molecular responses) | 36 months | |
Secondary | Chronic Graft-versus-host Disease (cGvHD) | 2 years after transplantation of the last patient included (this is intended to allow evaluations of all expected major molecular responses) | 36 months |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05691608 -
MoleculAr Profiling for Pediatric and Young Adult Cancer Treatment Stratification 2
|
N/A | |
Recruiting |
NCT04092803 -
Virtual Reality as a Distraction Technique for Performing Lumbar Punctures in Children and Young Adu
|
N/A | |
Active, not recruiting |
NCT02530463 -
Nivolumab and/or Ipilimumab With or Without Azacitidine in Treating Patients With Myelodysplastic Syndrome
|
Phase 2 | |
Completed |
NCT00948064 -
Vorinostat in Combination With Azacitidine in Patients With Newly-Diagnosed Acute Myelogenous Leukemia (AML) or Myelodysplastic Syndrome (MDS)
|
Phase 2 | |
Completed |
NCT04474678 -
Quality Improvement Project - "My Logbook! - I Know my Way Around!"; ("Mein Logbuch - Ich Kenne Mich Aus!")
|
N/A | |
Terminated |
NCT00801931 -
Double Cord Blood Transplant for Patients With Malignant and Non-malignant Disorders
|
Phase 1/Phase 2 | |
Recruiting |
NCT03948529 -
RevErsing Poor GrAft Function With eLtrombopag After allogeneIc Hematopoietic Cell trAnsplantation
|
Phase 2 | |
Completed |
NCT01682226 -
Cord Blood With T-Cell Depleted Haplo-identical Peripheral Blood Stem Cell Transplantation for Hematological Malignancies
|
Phase 2 | |
Completed |
NCT00003270 -
Chemotherapy, Radiation Therapy, and Umbilical Cord Blood Transplantation in Treating Patients With Hematologic Cancer
|
Phase 2 | |
Active, not recruiting |
NCT02723994 -
A Phase 2 Study of Ruxolitinib With Chemotherapy in Children With Acute Lymphoblastic Leukemia
|
Phase 2 | |
Terminated |
NCT02469415 -
Pacritinib for Patients With Lower-Risk Myelodysplastic Syndromes (MDS)
|
Phase 2 | |
Recruiting |
NCT04856215 -
90Y-labelled Anti-CD66 ab in Childhood High Risk Leukaemia
|
Phase 2 | |
Recruiting |
NCT06155188 -
Post-transplant PT/FLU+CY Promotes Unrelated Cord Blood Engraftment in Haplo-cord Setting in Childhood Leukemia
|
N/A | |
Completed |
NCT00001637 -
Immunosuppressive Preparation Followed by Blood Cell Transplant for the Treatment of Blood Cancers in Older Adults
|
Phase 2 | |
Active, not recruiting |
NCT04188678 -
Resiliency in Older Adults Undergoing Bone Marrow Transplant
|
N/A | |
Completed |
NCT02910583 -
Ibrutinib Plus Venetoclax in Subjects With Treatment-naive Chronic Lymphocytic Leukemia /Small Lymphocytic Lymphoma (CLL/SLL)
|
Phase 2 | |
Completed |
NCT01212926 -
Early Detection of Anthracycline Cardiotoxicity by Echocardiographic Analysis of Myocardial Deformation in 2D Strain
|
N/A | |
Terminated |
NCT00014560 -
Antibody Therapy in Treating Patients With Refractory or Relapsed Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia
|
Phase 1 | |
Recruiting |
NCT04977024 -
SARS-CoV-2 Vaccine (GEO-CM04S1) Versus mRNA SARS-COV-2 Vaccine in Patients With Blood Cancer
|
Phase 2 | |
Recruiting |
NCT05866887 -
Insomnia Prevention in Children With Acute Lymphoblastic Leukemia
|
N/A |