Refractory Leukemia, Relapsed Leukemia
Conditions
Keywords
HLA-mismatched GPBMC, allo-HSCT, relapsed leukemia, refractory leukemia
Brief summary
This is a Phase 1 clinical study designed to evaluate the safety, tolerability, and preliminary efficacy of chemotherapy combining with HLA-mismatched G-CSF mobilized peripheral blood mononuclear cell (GPBMC) infusion as a bridging therapy to allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with relapsed and refractory (R/R) leukemia.
Detailed description
Eligible patients will firstly receive chemotherapy combining with infusion of HLA-mismatched GPBMCs with the aim to reduce leukemia burden. Secondly, they will receive allo-HSCT per protocol. GPBMCs used in the first-step infusion will be derived from a sibling or unrelated donor, and GPBMCs used in the allo-HSCT procedure will be derived from an alternative donor, or the same donor (haploidentical/matched sibling/HLA 9-10 loci matched unrelated) as in the first step. The primary endpoint is the incidence of treatment-related adverse events (AEs) within 100 days post allo-HSCT, including graft-versus-host disease (GVHD), infection, organ dysfunction, and hematological toxicity. Secondary endpoints include overall survival (OS) at 1 and 2 years, progression-free survival (PFS), and graft-versus-host disease-free, relapse-free survival (GRFS).
Interventions
PROCEDUREChemotherapy
Available chemotherapy regimens include but not limited to FLAG (fludarabine, cytarabine, G-CSF), DAV (daunorubicin, cytarabine, venetoclax), IAV (idarubicin, cytarabine, venetoclax), VDCP (vincristine, daunorubicin, cyclophosphamide, prednisone), hyper-CVAD A (cyclophosphamide, vincristine, doxorubicin, dexamethasone), FC (fludarabine and cyclophosphamide), et al.
BIOLOGICALHLA-mismatched GPBMC infusion
HLA-mismatched GPBMCs are infused following chemotherapy.
PROCEDUREAllogeneic Stem Cell Transplantation
Patients receive conditioning including but not limited to fludarabine, cyclophosphamide, antithymocyte globulin (ATG), and total body irradiation (TBI). HLA-matched sibling/haploidentical/unrelated GPBMCs are infused at day 0. Post-transplant cyclophosphamide, tacrolimus/cyclosporin, and mycophenolate mofetil are administered as graft-versus-host disease prophylaxis.
Sponsors
Beijing 302 Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
15 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \>=15 years, male or female, non-limited by race or ethnicity. * Confirmed diagnosis of R/R leukemia and risk stratification according to the World Health Organization (WHO) 5th edition classification, based on histopathology and cytogenetics. * Adequate hepatic function including alanine transaminase (ALT) and aspartate aminotransferase (AST )\<= 3 × upper limit of normal(ULN), and total bilirubin \<= 1.5 × ULN. * Adequate renal function including serum creatinine \<= 2 × ULN or CrCl\>= 40mL/min. * LVEF measured by echocardiogram is within the normal range (LVEF \> 50%). * The subject must have one HLA mismatched donor who is \>= 18 years old to provide GPBMCs for the first-step infusion. If this donor is not qualified as an allo-HSCT donor, the subject must also have another donor who is \>= 18 years old and qualified as allo-HSCT donor (i.e., matched sibling, 9-10/10 loci matched unrelated, or haploidentical). In addition, the donor voluntarily donates hematopoietic stem cells and signs the consent form. Each subject (or his/her legal representatives) must sign the Informed Consent Form (ICF), indicating that he/she understands the purpose and procedures of research, and is willing to participate in research. * Donor inclusion criteria: The donor meets the institution's criteria for related peripheral blood hematopoietic stem cell donors. The donor must be able to tolerate the cell separation and collection process, and sign the Informed Consent Form.
Exclusion criteria
* Uncontrolled infection or hemorrhage. * Cardiovascular disease with clinical significance, such as uncontrolled or highly symptomatic cardiac arrhythmias, congestive heart failure, or myocardial infarction within 6 months prior to screening, or New York Heart Association (NYHA) function class 3 (moderate) or class 4 (severe) heart disease. * Uncontrolled autoimmune disease or requiring immunosuppression treatment. * History of severe blood infusion reaction. * Nursing women, women of childbearing potential with positive urine pregnancy test, or women of childbearing potential who are not willing to maintain adequate contraception. * Psychiatric disorder or cognitive impairment that in the researcher's judgment would make the subject not likely to adhere to the protocol requirements. * Major surgery within 4 weeks prior to enrollment. * Life-threatening illness other than leukemia or uncontrolled intercurrent illness.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Graft-Versus-Host Disease (GVHD) | Measured up to 2 years after the last participant is enrolled | Including acute GVHD (aGVHD) and chronic GVHD (cGVHD), assessed per international universal criteria (e.g., Glucksberg classification). |
| Infections | Measured up to 2 years after the last participant is enrolled | Covering bacterial, viral, fungal infections (e.g., pneumonia, sepsis, cytomegalovirus infection), confirmed based on clinical symptoms, laboratory tests, and etiological evidence. |
| Hematological Toxicity | Measured up to 2 years after the last participant is enrolled | Including neutropenia, thrombocytopenia, anemia, etc., graded according to the Common Terminology Criteria for Adverse Events (CTCAE) standards. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Measured up to 4 years after the last participant is enrolled | Time from the completion of allo-HSCT to death from any cause. |
| Treatment-Related Mortality (TRM) | Measured up to 2 years after the last participant is enrolled | TRM is defined as the death related to treatment instead of disease progression. |
| Progression-Free Survival (PFS) | Measured up to 4 years after the last participant is enrolled | Time from the completion of allo-HSCT to disease progression, relapse, or death from any cause. |
| Graft-Versus-Host Disease-Free, Relapse-Free Survival (GRFS) | Measured up to 4 years after the last participant is enrolled | Time from the completion of allo-HSCT to the first occurrence of any of the following events: grade 3-4 acute GVHD, chronic GVHD requiring systemic treatment, disease relapse, or death. |
Countries
China
Contacts
Primary ContactBo Cai, MD
Backup ContactYangyang Lei, MD
Outcome results
None listed