Chronic Myelomonocytic Leukemia (CMML)
Conditions
Keywords
Chronic Myelomonocytic Leukemia (CMML), Hematopoietic Stem Cell Transplantation (HSCT), Thiotepa
Brief summary
This is a prospective, single-arm clinical study. It aims to evaluate the effectiveness and safety of a conditioning regimen containing thiotepa (in combination with busulfan and fludarabine, with or without ATG) of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with chronic myelomonocytic leukemia (CMML) who have an intermediate-2 or high-risk prognosis. The main goal is to evaluate 1 year RFS and OS. Other goals include assessing engraftment, overall survival, transplant-related complications, and side effects. A total of 31 participants will be enrolled.
Interventions
DRUGTBF regimen
Intravenous thiotepa 5 mg/kg/d on days -11,-10; busulfan 3.2 mg/kg/d on days -8,-7,-6; fludarabine 30 mg/m²/d on days -6 to -2; ATG per donor type (haplo/unrelated: 2.5 mg/kg/d days -5 to -2; MSD: 1.125 mg/kg/d days -5 to -2). Allogeneic stem cells infused on day 0. GVHD prophylaxis: CsA, MMF, MTX per protocol.
Sponsors
Peking University People's Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years, any sex/gender. * Confirmed diagnosis of chronic myelomonocytic leukemia (CMML) according to the 2022 WHO classification. * Intermediate-2 or high-risk CMML based on CPSS or CPSS-mol score, and planned to receive allo-HSCT. * Has a suitable hematopoietic stem cell donor: * For haploidentical donor: at least 5/10 HLA match at HLA-A, -B, -C, -DQB1, and -DRB1. * For unrelated donor: at least 9/10 HLA match at the same five loci. * For matched sibling donor: 10/10 HLA match at the same five loci. * Hematopoietic cell transplantation comorbidity index (HCT-CI) ≤ 2, with generally good health and no significant organ abnormalities or major comorbidities. * Adequate organ function as defined below: * Left ventricular ejection fraction (LVEF) ≥ 50%, and no uncontrolled tachycardia or bradycardia-tachycardia syndrome. * Total bilirubin ≤ 1.5 × upper limit of normal (ULN); ALT ≤ 2 × ULN; AST ≤ 2 × ULN. * Serum creatinine ≤ 1.5 × ULN. * Baseline oxygen saturation \> 92%. * Pulmonary function: DLCO (corrected for hemoglobin) ≥ 40%, FEV1 ≥ 50%. * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. * Agrees not to participate in any other interventional study during the treatment period. * Willing and able to provide written informed consent, understand the nature, purpose, and procedures of the study, and voluntarily comply with study requirements.
Exclusion criteria
* Previous allogeneic HSCT for CMML that later relapsed. * Unwilling or unable to receive the study treatment regimen. * Active hepatitis B or C, or chronic active hepatitis; known human immunodeficiency virus (HIV) infection. * Active uncontrolled infection, including: hemodynamic instability related to infection, new or worsening signs/symptoms of infection, new infection lesions on imaging, or persistent fever without explanation despite no symptoms/signs. * History of stroke or intracranial hemorrhage within 6 months before enrollment. * Known pregnancy (positive urine pregnancy test), or currently breastfeeding. * Diagnosis of another malignancy within the past 2 years, except for localized skin cancer, superficial bladder cancer, carcinoma in situ of the cervix, breast cancer, or localized prostate cancer (Gleason score ≤ 6) that has been treated with curative intent. * Any other condition that, in the investigator's judgment, makes the patient unsuitable for study participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| One-year relapse-free survival (RFS) after allogeneic hematopoietic stem cell transplantation | At 12 months after allogeneic hematopoietic stem cell transplantation. | Time from stem cell infusion to hematologic/extramedullary relapse or death, censored at 12 months for event-free participants. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| One-year overall survival (OS) | At 12 months after allogeneic hematopoietic stem cell transplantation. | Overall survival is defined as the time from stem cell infusion to death from any cause. Participants alive at 12 months are censored at the last follow-up. |
| One-year cumulative incidence of relapse (RR) | At 12 months after allogeneic hematopoietic stem cell transplantation. | Relapse is defined as recurrence of CMML . Non-relapse mortality is treated as a competing risk. |
| One-year non-relapse mortality (NRM) | At 12 months after allogeneic hematopoietic stem cell transplantation. | Non-relapse mortality is defined as death from any cause other than disease relapse or progression. Relapse is treated as a competing risk. |
| Regimen toxicity at day +30 | Up to day +30 post-transplant | Toxicity is graded according to NCI CTCAE v5.0. Any grade 3-5 non-hematologic toxicity occurring within 30 days after stem cell infusion is reported. |
| Incidence and severity of adverse events (AEs) | At 12 months after allogeneic hematopoietic stem cell transplantation. | AEs are coded using MedDRA and graded per NCI CTCAE v5.0. All AEs, serious AEs (SAEs), and AEs leading to treatment discontinuation are summarized. |
| Incidence and severity of acute graft-versus-host disease (aGVHD) | Up to day +100 post-transplant | Acute GVHD is diagnosed and graded according to the modified Glucksberg criteria or MAGIC criteria. Both overall incidence and grade II-IV/III-IV severity are reported. |
| Incidence and severity of chronic graft-versus-host disease (cGVHD) | From day +100 up to 1 year post-transplant | Chronic GVHD is diagnosed and graded according to the NIH consensus criteria (mild, moderate, severe). Overall incidence and severity distribution are reported. |
Countries
China
Contacts
CONTACTYuqian Sun, MD
CONTACTXueyi Luo, MD
PRINCIPAL_INVESTIGATORYuqian Sun, MD
Peking University People's Hospital
Outcome results
None listed