Refractory Thrombocytopenia
Conditions
Keywords
Refractory thrombocytopenia, Megakaryocyte
Brief summary
A study to evaluate the safety, efficacy, and pharmacokinetics of MegaLT in treating refractory thrombocytopenia following radiotherapy, chemotherapy, or transplantation.
Detailed description
A single-center, open-label, dose-escalation study to assess the safety, efficacy, and pharmacokinetics of MegaLT for treating refractory thrombocytopenia following radiotherapy, chemotherapy, or transplantation.
Interventions
BIOLOGICALMegaLT injection
Three dose groups were set: 1×10\^6/kg, 5×10\^6/kg, and 1×10\^7/kg. The dose escalation was carried out in ascending order using a "3+3" design. To ensure participant safety, enrollment followed a "1+2" rule. Specifically, the first participant in each dose group received the cell infusion and was observed for 14 days. If no dose-limiting toxicity (DLT) was observed, the remaining two participants could then be enrolled and receive cell therapy at the same dose level.
Sponsors
Anhui Provincial Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Subjects will receive cell infusions sequentially according to their enrollment order, with three planned dose levels of: 1×10⁶/kg, 5×10⁶/kg, and 1×10⁷/kg.
Eligibility
Sex/Gender
ALL
Age
4 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age between 4 and 75 years (inclusive) at screening; gender is not restricted; * Diagnosed with refractory thrombocytopenia following radiotherapy/chemotherapy or transplantation; * Adequate organ function：Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) \< 2.5\*upper limit of normal (ULN); Serum creatinine \< 1.5\* ULN; Total bilirubin level \< 1.5\* ULN; Coagulation function: International Normalized Ratio (INR) ≤ 1.5\* ULN, Activated Partial Thromboplastin Time (APTT) ≤ 1.5\*ULN; Hemoglobin ≥ 60 g/L, or hemoglobin maintained at this level after transfusion; Absolute neutrophil count (ANC) ≥ 1.0×10\^9/L; * Eastern Cooperative Oncology Group (ECOG) performance status of 0-2; * Voluntarily participating in the clinical trial, with full understanding of the trial details and having signed the informed consent form.
Exclusion criteria
* Patients with any malignant tumor relapse; * Pregnant or breastfeeding women; * Life expectancy less than 3 months; * Severe infections or severe concurrent conditions such as heart, liver, lung, kidney, neurological, or metabolic diseases; * History of severe thrombotic events or known thrombotic risk factors. Exceptions: Participants for whom the potential benefits of the study, as determined by the investigator, outweigh the potential risks of thromboembolic events; * Uncontrolled infectious or other serious diseases, including but not limited to infections (e.g., HIV positive), congestive heart failure, unstable angina, arrhythmias, psychiatric disorders, or conditions that limit the ability to meet study requirements or pose unpredictable risks as judged by the primary physician; * Active hepatitis B or C infection; * Refractory thrombocytopenia post-transplant with Grade III-IV acute graft-versus-host disease (GVHD) \[according to NIH standards\] or severe chronic GVHD (NIH 2014 standards); * History of organ transplantation or planned organ transplantation (excluding hematopoietic stem cell transplantation); * Participation in another clinical study within 30 days prior to the baseline visit, involving any investigational drug or device; observational studies are allowed; * Any other conditions deemed by the investigator to make the participant unsuitable for the clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Event(AE) | From the date of initial infusion to 1 year after initial infusion | Number of treatment-related adverse events as assessed by CTCAE v4.0 |
| Incidence of bleeding events | From the date of initial infusion to 1 year after initial infusion | The incidence of bleeding events after initial infusion |
| The cumulative incidence and grade of graft-versus-host disease (GVHD) including acute and chronic GVHD | From the date of initial infusion to 1 year after initial infusion | The occurrence incidence and grade of GVHD after transplantation |
| The probability of GVHD-free, relapse-free survival(GRFS) | From the date of initial infusion to 1 year after initial infusion | The composite endpoint of GRFS was defined as the first events occurring after transplantation among Grade III to IV aGVHD, moderate to severe cGVHD, relapse, or death for any reason. |
| Overall response rate (ORR) | 4 weeks after initial infusion | Percentage of participants achieved Complete response(CR) or Partial response(PR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate (ORR) | 1, 2 and 8 weeks after initial infusion | Percentage of participants achieved Complete Response(CR) or Partial Response(PR) |
| Complete remission (CR) rate | 1, 2, 4 and 8 weeks after initial infusion | CR was defined as a platelet count ≥ 50×10\^9/L without platelet transfusions for 7 consecutive days |
| partial response rate (PR) | 1, 2, 4 and 8 weeks after initial infusion | PR was defined as a platelet count \< 50×10\^9/L but above the baseline level at enrollment, with a sustained increase for 7 consecutive days without platelet transfusions |
| Changes in platelet counts | before treatment and at 1, 2, 4, and 8 weeks after treatment | Changes in platelet counts before treatment and at 1, 2, 4, and 8 weeks after treatment |
| Median time of platelet count ≥ 50×10^9/L | 1 year after initial infusion | Platelet count ≥50×10\^9/L for 3 consecutive days without platelet transfusions for 7 consecutive days |
| Median time of platelet count ≥ 100×10^9/L | 1 year after initial infusion | Platelet count ≥50×10\^9/L for 3 consecutive days without platelet transfusions for 7 consecutive days |
| Total platelet transfusion during 4 weeks of treatment | 4 weeks after initial infusion | Total platelet transfusion during 4 weeks of treatment |
| neutrophil reconstitution | 1 year after initial infusion | Neutrophil engraftment time was defined as the first of three consecutive days during which the neutrophil count was at least 0.5×10\^9/L |
| erythroid reconstitution | 1 year after initial infusion | Red blood count (RBC) engraftment time was defined as the first day of achieving a reticulocyte count greater than 1% for 3 consecutive days. |
| Megakaryocyte levels in bone marrow smears | before treatment and 2 and 4 weeks after treatment | Megakaryocyte levels in bone marrow smears |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORXiaoyu Zhu, Ph.D
The First Affiliated Hospital of University of Science and Technology of China
Outcome results
None listed