Organ-Sparing Marrow-Targeted Irradiation Before Stem Cell Transplant in Treating Patients With High-Risk Hematologic Malignancies
Condition: Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Hematologic Neoplasms; Myelodysplastic Syndromes; Syndrome; Recurrence
Study type: Interventional
Phase: Phase 1

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.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. To assess feasibility and tolerability of OSMI based hematopoietic stem cell transplant
      (HSCT) as defined by transplant-related mortality (TRM) at day 30 as well as rate of grade
      II/III organ toxicity (defined by Bearman Regimen-Related Toxicities Scale) attributable to
      conditioning occurring within 30 days.

      SECONDARY OBJECTIVES:

      I. Day 100 transplant-related mortality (TRM). II. Donor chimerism assessment at day 100 (to
      assess failure of engraftment rate).

      III. Incidence of acute graft-versus-host disease (aGVHD) by day 100. IV. Incidence of
      chronic GVHD at one year. V. Cumulative incidence of grade II organ toxicity through day 100.
      VI. Rate and kinetics of hematopoietic recovery. VII. Incidence of graft failure (primary and
      secondary). VIII. Rate of infectious complications. IX. Cumulative incidence of relapse,
      overall survival, and progression-free survival at 1 year.

      OUTLINE:

      CONDITIONING REGIMEN: Patients undergo organ-sparing marrow irradiation twice daily (BID) on
      days -6 to -4 and receive cyclophosphamide intravenously (IV) over 1-2 hours every 24 hours
      on days -3 to -2. Patients with an unrelated donor also receive anti-thymocyte globulin every
      24 hours on days -4 to -2.

      GVHD PROPHYLAXIS: Patients receive tacrolimus IV or orally (PO) beginning on day -1 and
      continuing for at least 6 months and methotrexate IV on days 1, 3, 6, and 11.

      TRANSPLANT: Patients undergo allogeneic peripheral blood progenitor cell or bone marrow
      transplant on day 0.

      After completion of study treatment, patients are followed up weekly for 12 weeks, at day
      100, and then at 6 and 12 months.
    

Intervention name(s): radiation therapy; cyclophosphamide; anti-thymocyte globulin; tacrolimus; methotrexate; allogeneic bone marrow transplantation; allogeneic hematopoietic stem cell transplantation; peripheral blood stem cell transplantation; laboratory biomarker analysis
Intervention type(s): Radiation; Drug; Biological; Drug; Drug; Procedure; Procedure; Procedure; Other
Intervention description(s): Undergo organ-sparing marrow irradiation BID on days -6 to -4; Given IV over 1-2 hours every 24 hours on days -3 to -2.; Given IV or PO; Given IV; Undergo allogeneic peripheral blood progenitor cell or bone marrow transplant on day 0; Undergo allogeneic peripheral blood progenitor cell or bone marrow transplant; Undergo allogeneic peripheral blood progenitor cell or bone marrow transplant; Correlative studies
Other intervention name(s): irradiation; radiotherapy; therapy, radiation; CPM; CTX; Cytoxan; Endoxan; Endoxana; ATG; ATGAM; lymphocyte immune globulin; Thymoglobulin; FK 506; Prograf; amethopterin; Folex; methylaminopterin; Mexate; MTX; bone marrow therapy, allogeneic; bone marrow therapy, allogenic; transplantation, allogeneic bone marrow; transplantation, allogenic bone marrow; PBPC transplantation; PBSC transplantation; peripheral blood progenitor cell transplantation; transplantation, peripheral blood stem cell
Intervention MeSH terms: Cyclophosphamide; Methotrexate; Tacrolimus; Thymoglobulin; Antilymphocyte Serum; Immunoglobulins
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment