Organ-Sparing Marrow-Targeted Irradiation Before Stem Cell Transplant in Treating Patients With High-Risk Hematologic Malignancies

• Status: Unknown status
• Trial end date: 2019-12-31
• Target enrollment: 0
• Participant gender: All

Summary

This pilot clinical trial aims to assess feasibility and tolerability of using an LINAC based "organ-sparing marrow-targeted irradiation" to condition patients with high-risk hematological malignancies who are otherwise ineligible to undergo myeloablative Total body irradiation (TBI)-based conditioning prior to allogeneic stem cell transplant. The target patient populations are those with ALL, AML, MDS who are either elderly (>50 years of age) but healthy, or younger patients with worse medical comorbidities (HCT-Specific Comorbidity Index Score (HCT-CI) > 4). The goal is to have the patients benefit from potentially more efficacious myeloablative radiation based conditioning approach without the side effects associated with TBI.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Ohio State University Comprehensive Cancer Center
• Treatments: Antilymphocyte Serum; Cyclophosphamide; Immunoglobulins; Methotrexate; Tacrolimus; Thymoglobulin

Criteria

Inclusion Criteria:

• Patients with a diagnosis of acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or myelodysplastic syndromes (MDS) with fewer than 10% myeloblasts or lymphoblasts in the bone marrow and no blasts in the peripheral blood on morphologic analysis performed within 30 days of start of the conditioning regimen; if remission bone marrow is available beyond 30 days a new bone marrow evaluation is required to assess remission status

• The diagnosis of AML, ALL, or MDS will be based on World Health Organization (WHO) criteria

• Pre-transplant bone marrow sample must be evaluable for assessment of remission status (i.e. aspirate smear containing particles and/or evaluable bone marrow core biopsy)

• Patients with leukemia infiltration in the central nervous system (CNS) are eligible if cerebrospinal fluid (CSF) cytospin is negative for myeloblasts or lymphoblasts at time of enrollment

• If the patient has an intra-abdominal chloroma on presentation, and has a partial response or complete response to treatment (size reduction of chloroma and marrow blast < 10%), the patient is eligible; however the chloroma must be included as part of the treatment target

• For patients receiving treatment of their AML, MDS or ALL prior to transplantation:

• Interval between the start of a cycle of conventional cytotoxic chemotherapy and the start of conditioning regimen must be at least 30 days

• Interval between completing treatment with a hypomethylating agent or other non-cytotoxic chemotherapy and the start of conditioning regimen must be at least 10 days

• Hematopoietic Cell Transplantation-Specific Comorbidity Index score (HCT-CI) =< 4 for patients in Cohort 1 and > 4 for Cohort 2

• Patient must be able to lie still in full body cast for 45 minutes

• Must have a suitable donor defined as a sibling matched at 5/6 or 6/6 antigens (human leukocyte antigen [HLA]-A, B, and DRB1) or an unrelated volunteer matched at 7/8 or 8/8 HLA alleles (HLA-A, B, C, and DRB1)

• Signed informed consent

• DONOR: "High resolution" typing at HLA-A, B, C and DRB1 alleles

• Single antigen mismatch for siblings and single allele mismatch for volunteer unrelated donors is acceptable

• Donors must be >= 17 years of age

Exclusion Criteria:

• Circulating peripheral blood myeloblasts or lymphoblasts on morphologic analysis from time of last treatment to time of enrollment

• Prior allograft or prior autograft

• Active CNS disease as identified by positive CSF cytospin at time of enrollment

• Karnofsky performance score < 70

• Symptomatic uncontrolled coronary artery disease or ejection fraction < 40%

• Total bilirubin >= 2 x the upper limit of normal

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >= 3 x the upper limit of normal

• Diffusion capacity of the lung for carbon monoxide (DLCO) < 40%

• Forced expiratory volume in one second (FEV1) < 50% (corrected for hemoglobin)

• Receiving supplementary continuous oxygen

• Creatinine clearance < 50 mL/min/1.73m^2

• Patients with active uncontrolled bacterial, viral or fungal infections (undergoing appropriate treatment and with progression of clinical symptoms)

• Patients seropositive for the human immunodeficiency virus (HIV)

• Females who are pregnant or breastfeeding

• Fertile men and women unwilling to use contraceptive techniques during and for 12 months following treatment

• Patients who had prior radiation to more than 20% bone marrow containing areas or to any areas exceeding 2000 cGy

• DONOR:

• Donors will be excluded if they are an identical twin of the recipient

• Females who are pregnant (positive serum beta human chorionic gonadotropin beta [β HCG]) or uninterruptible breastfeeding

• HIV seropositive

• Donors receiving experimental therapy or investigational agents unless approved by the protocol chair