Total Marrow and Lymphoid Irradiation as Conditioning Regimen Before Hematopoietic Cell Transplantation in Patients With Myelodysplastic Syndrome or Acute Leukemia

Acute Myeloid Leukemia Clinical Trial

Official title: Phase II Study of Evaluating the Efficacy of Total Marrow and Lymphoid Irradiation (TMLI) as the Conditioning Regimen for HLA-Haploidentical Hematopoietic Cell Transplantation in Patients With Myelodysplasia or Acute Leukemia

Status Recruiting

Clinical Trial Summary

This phase II trial studies how well total marrow and lymphoid irradiation works as a conditioning regimen before hematopoietic cell transplantation in patients with myelodysplastic syndrome or acute leukemia. Total body irradiation can lower the relapse rate but has some fatal side effects such as irreversible damage to normal internal organs and graft-versus-host disease (a complication after transplantation in which donor's immune cells recognize the host as foreign and attack the recipient's tissues). Total body irradiation is a form of radiotherapy that involves irradiating the patient's entire body in an attempt to suppress the immune system, prevent rejection of the transplanted bone marrow and/or stem cells and to wipe out any remaining cancer cells. Intensity-modulated radiation therapy (IMRT) is a more recently developed method of delivering radiation. Total marrow and lymphoid irradiation is a method of using IMRT to direct radiation to the bone marrow. Total marrow and lymphoid irradiation may allow a greater dose of radiation to be delivered to the bone marrow as a preparative regimen before hematopoietic cell transplant while causing less side effects to normal organs than standard total body irradiation.

Clinical Trial Description

PRIMARY OBJECTIVE: I. Evaluate the efficacy of the haploidentical hematopoietic cell transplantation (haploHCT) total marrow and lymphoid organ irradiation (TMLI), with high dose post-transplant cyclophosphamide (PTCy) as graft-versus host disease (GvHD) prophylaxis, as assessed by 1-year graft versus (vs) host disease-free relapse-free survival (GRFS) rate in each arm (Arm A: patients with acute myeloid leukemia [AML] or myelodysplastic syndrome [MDS] and Arm B: Patients with acute lymphoblastic leukemia [ALL]). SECONDARY OBJECTIVES: I. Estimate overall survival (OS), cumulative incidences of relapse/disease progression, and non-relapse mortality (NRM) in each arm at 100 days, and 1 year post-transplant. II. Estimate rate of relapse and non-relapse mortality (NRM) at 1 year post-transplant. III. Estimate rates of acute and chronic GvHD, infections, complete remission and neutrophil recovery. IV. Describe and characterize cytokine release syndrome (CRS) post-haploidentical HCT with TMLI as conditioning regimen and PTCy as GvHD prophylaxis as assessed by incidence, frequency and severity. V. Further evaluate the safety of this regimen by assessing: Va. Adverse events: type, frequency, severity, attribution, time course, duration. Vb. Complications: including acute/chronic GVHD, infection and delayed engraftment. EXPLORATORY OBJECTIVES: I. Characterize minimal residual disease from bone marrow aspirates and investigate the possible association between TMLI-based regimen and patient's disease status. II. Describe the kinetics of immune cell recovery. III. Describe the kinetics of serum pro-inflammatory cytokines and GvHD biomarkers. IV. Longitudinal and spatial assessment of TMLI effect on bone marrow environment. V. Cellular and molecular assessment of TMLI effect on bone marrow environment and TMLI effect on the engraftment and disease relapse. OUTLINE: CONDITIONING: Patients receive fludarabine intravenously (IV) once daily (QD) on days -7 to -5, and undergo TMLI twice daily (BID) on days -4 to 0 in the absence of disease progression or unacceptable toxicity. TRANSPLANT: Patients undergo hematopoietic cell transplantation on day 0. GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV QD on days 3-4 in the absence of disease progression or unacceptable toxicity. Beginning on day 5, patients also receive granulocyte colony stimulating factor and tacrolimus/mycophenolate mofetil per institutional standard. After completion of study treatment, patients are followed up twice weekly for the first 100 days post-transplant, twice monthly until 6 months post-transplant, monthly until patient discontinues immunosuppressive therapy, and then yearly for 2 years. ;

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Acute Myeloid Leukemia
• High Risk Myelodysplastic Syndrome
• Leukemia
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Preleukemia
• Syndrome

• NCT number: NCT04262843
• Study type: Interventional
• Source: City of Hope Medical Center
• Status: Recruiting
• Phase: Phase 2
• Start date: February 7, 2020
• Completion date: August 4, 2025