Reduced-intensity conditioning to lower treatment-related mortality in stem cell transplant patients
A 2 Step Approach to Haploidentical Transplant Using Radiation-Based Reduced Intensity Conditioning
This study is testing a new way to prepare patients for a stem cell transplant to see if it can lower the risk of serious treatment-related complications.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 63 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Thomas Jefferson University Academic / other |
| Drugs / interventions | Chemotherapy, Radiation, cyclophosphamide, fludarabine |
| Locations | 1 site (Philadephia, Pennsylvania) |
| Trial ID | NCT05031897 on ClinicalTrials.gov |
What this trial studies
This phase II clinical trial investigates a modified conditioning regimen aimed at reducing treatment-related mortality (TRM) in patients undergoing hematopoietic stem cell transplant (HSCT) for various hematological malignancies. The study compares two cohorts: one receiving a radiation-based approach and the other a chemotherapy-based approach, both involving a combination of fludarabine, total-body irradiation, donor lymphocyte infusion, and cyclophosphamide. The primary objective is to assess the two-year cumulative incidence of TRM, while secondary objectives include evaluating relapse rates, engraftment consistency, immune recovery, and the incidence of graft versus host disease (GVHD). Patients will be monitored through various assessments including bone marrow biopsies and blood sample collections throughout the study.
Who should consider this trial
Good fit: Ideal candidates include patients with hematological malignancies such as acute lymphoblastic leukemia, acute myeloid leukemia, and chronic lymphocytic leukemia who are eligible for HSCT.
Not a fit: Patients with advanced disease stages or those who have previously undergone myeloablative therapy may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could significantly reduce the risk of treatment-related mortality in patients undergoing HSCT, improving overall survival rates.
How similar studies have performed: Other studies have shown promise with reduced-intensity conditioning regimens, suggesting potential for success in this approach.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Radiation-based cohort diagnoses: * Acute myeloid leukemia * Acute lymphoid leukemia in remission * Myelodysplasia (MDS) * Chronic lymphocytic leukemia (CLL) with no or minimal lymph node involvement * Multiple myeloma * Chronic myeloid leukemia * Myelofibrosis * Myeloid malignancy not otherwise specified * Chronic myelomonocytic leukemia * Essential thrombocytopenia or polycythemia vera * T cell leukemia * T cell lymphoma without significant lymph node disease burden * Any hematological malignancy or dyscrasia not cited above in which HSCT is potentially curable * Any patient who has a hematological disease that would normally be treated on a myeloablative study, but is prevented from doing so by factors in their past medical history. Examples are patients with previous treatment with radiation therapy precluding total-body irradiation (TBI), or a past history of myeloablative therapy, precluding a 2nd myeloablative regimen. * Patients must have a donor who is one-haplotype mismatched (number of mismatches in either direction not considered) * Chemotherapy-based cohort diagnoses: * Hodgkin or non-Hodgkin lymphoma * Small lymphocytic lymphoma/CLL * Any other diagnosis in which chemotherapy is thought to be superior to radiotherapy for treatment of the disease * Hematological malignancy in patients who cannot receive \> 2 Gy radiation * Aplastic anemia and other non-malignant hematologic dyscrasias * Patients must have a donor who is one-haplotype mismatched (number of mismatches in either direction not considered) * Human leukocyte antigen (HLA) identical cohort diagnoses: \* Patients in this group will be treated in parallel to the radiation-based cohort or the chemotherapy-based group based on what category their diagnosis falls into. However, these patients will have HLA identical related donors (one-antigen cross-over event included). * Left ventricular ejection fraction of \>= 50% * Diffusion lung capacity of oxygen \>= 50% and forced expiratory volume at 1 second \>= 50% of predicted corrected for hemoglobin * Serum bilirubin =\< 1.8 * Aspartate aminotransferase or alanine aminotransferase =\< 2.5 x upper limit of normal * Creatinine clearance of \>= 60 mL/min * Patients must have adequate Karnofsky performance status (KPS) and Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) scores: * Patients \< age 60 years must have a KPS of \>= 60% and an HCT-CI score of 5 or less * Patients aged 60 to 65 years must have a KPS of \>= 60% and an HCT-CI score of 4 or less * Patients aged 66 to 69 years must have a KPS of 90% and an HCT-CI score of 3 or less * Patients aged 70 years or more must have a KPS of 90% and an HCT-CI score of 2 or less * (Patients with greater than the allowable HCT-CI points for age can be enrolled for trial with approval of the principal investigator (PI) and at least 1 co-investigator (CI) not on the primary care team of the patient). This is an adjustment to account for healthy patients who meet the spirit of this protocol but have histories that result in higher than guideline HCT-CI points. An example is a patient with a solid tumor malignancy in their remote history (adds 3 points to HCT-CI total) where the treatment for the malignancy occurred years to decades before and there has been complete recovery of toxicities * Patients must be willing to use contraception if they have childbearing potential * Patient or patient's guardian is able to give informed consent * Patients should have a life expectancy of \>= 6 months for reasons other than their underlying hematologic/oncologic disorder * Patients with evidence of another malignancy, exclusive of a skin cancer that requires only local treatment, should not be enrolled on this protocol * Patients should not be: * Human immunodeficiency virus positive * Have active involvement of the central nervous system with malignancy. This can be documented by a normal neurological exam, magnetic resonance imaging (MRI) of the head, and/or a negative cerebral spinal fluid analysis * Pregnant or breastfeeding
Where this trial is running
Philadephia, Pennsylvania
- Sidney Kimmel Cancer Center at Thomas Jefferson University — Philadephia, Pennsylvania, United States (Recruiting)
Study contacts
- Principal investigator: Usama Gergis, MD — Thomas Jefferson University
- Study coordinator: Usama Gergis, MD
- Email: usama.gergis@jefferson.edu
- Phone: 215-503-2455
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.