Donor Stem Cell Transplant in Treating Patients with High Risk Hematologic Malignancies
- This treatment is for patients with high risk hematologic malignancies; high risk is defined as: * Any patient with a hematologic malignancy in which allogeneic HSCT is pursued with the expectation of cure; patients may have post-treatment residual disease, but the disease should be stable or minimally progressive and must be responsive to chemotherapy * Any patient with an untreated hematologic malignancy in which allogeneic HSCT is thought to be the sole or the best option for cure and in which prior treatment is unlikely to meaningfully address the disease * Patients without morphologic evidence of disease but with high risk features which would predict for relapsed despite remission at HSCT such as adverse cytogenetics, third (3rd) or greater complete response (CR), or failure to recover peripheral blood counts to normal ranges; while these patients do not have detectable disease by current methods, like all patients they have non-detectable disease which in their case is highly aggressive * Patients with uncommon diagnoses in which allogeneic HSCT is thought to be beneficial, but are not comparable to the majority of patients on this protocol will not counted in the statistical aims of the study and will be reported descriptively. The principal investigator (PI) and at least one cooperative investigator (Co-I) must document this exception in the study binder and the rationale for descriptive report. An example of a patient who may meet this criteria is someone with a malignancy that is an overlap of two different diagnoses or one whose malignancy is difficult to categorize. While this circumstance is expected to be rare, it will prevent patients with rare diagnoses to be treated off study, and it will help maintain homogeneity of the study population
- Patients must have one related donor who is human leukocyte antigen (HLA) mismatched in the GVHD direction at two or more HLA loci
- Left ventricular ejection fraction (LVEF) of >= 50%
- Carbon monoxide diffusing capability test (DLCO) (adjusted for hemoglobin) >= 50% of predicted and forced expiratory volume in 1 second (FEV-1) >= 50%
- Serum bilirubin =< 1.8
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)
- Creatinine clearance of >= 60 ml/min
- Karnofsky performance status (KPS) of >= 80% on the modified KPS tool
- Patients must be willing to use contraception if they have childbearing potential
- Able to give informed consent
- Modified KPS of < 80%
- > 5 comorbidity points on the Hematopoietic Cell Transplant Co-Morbidity Index (HCT CI) (patients with greater than 5 points will be allowed for trial with approval of the principal investigator [PI] and at least 1 cooperative investigator [Co-I] 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 HCT-CI 5 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
- Human immunodeficiency virus (HIV) positive
- Active involvement of the central nervous system with malignancy
- Psychiatric disorder that would preclude patients from signing an informed consent
- Pregnancy, or unwillingness to use contraception if they have childbearing potential
- Patients with life expectancy of =< 6 months for reasons other than their underlying hematologic/oncologic disorder
- Alemtuzumab treatment within 8 weeks of HSCT admission
- Anti-thymocyte globulin (ATG) within 8 weeks of HSCT admission
- Inability to tolerate cyclophosphamide or undergo total body irradiation at the doses specified in the treatment plan
I. To assess 2 year probability of overall survival (OS) in high risk patients undergoing a myeloablative 2 step hematopoietic stem cell transplantation (HSCT) utilizing strategies to decrease relapse.
I. To assess relapse incidence at 2 years post-HSCT of patients undergoing treatment on this protocol.
II. To assess regimen related toxicity and graft versus host disease (GVHD) incidence at 2 years post-HSCT and severity in patients undergoing treatment on this protocol.
III. To assess the consistency and pace of engraftment.
IV. To assess the pace of T cell and B cell immune recovery.
Patients undergo total body irradiation (TBI) twice daily (BID) on days -10 to -8 and donor lymphocyte infusion (DLI) on day -6. Patients receive cyclophosphamide intravenously (IV) on days -3 and -2, tacrolimus IV beginning on day -1 and then orally (PO) at least 2 or 3 days prior to discharge with taper starting on day 42, and mycophenolate mofetil IV BID on days -1 to 28. Patients undergo HSCT on day 0.
After completion of study treatment, patients are followed up for 2 years.
Trial Phase Phase II
Trial Type Treatment
Thomas Jefferson University Hospital
- Primary ID 16D.606
- Secondary IDs NCI-2017-00094
- Clinicaltrials.gov ID NCT03032783