Donor Stem Cell Transplant in Treating Patients With High-Risk Hematologic Malignancies
Condition: Hematologic Malignancy
MeSH terms: Neoplasms; Hematologic Neoplasms
Intervention: Total Body Irradiation; Donor Lymphocyte Infusion (DLI); Cyclophosphamide; Tacrolimus; Mycophenolate mofetil; Allogeneic hematopoietic stem cell transplantation; Laboratory biomarker analysis
Intervention description: Undergo TBI; Undergo DLI; Given IV; Given IV or PO; Given IV or PO; Undergo allogeneic HSCT; Correlative studies
Intervention MeSH terms: Mycophenolic Acid; Cyclophosphamide; Tacrolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: allogeneic stem cell transplant; TJU 2 Step; HSCT; Hematopoietic stem cell transplantation

Summary:

      The purpose of this research study is to examine the survival of patients undergoing
      partially matched hematopoietic stem cell transplant (HSCT) on a new type of treatment
      approach, which has been developed specifically for patients who have evidence of their
      disease at the time of transplant. In this research study, a way of strengthening the
      response of the donor cells against the disease has been developed. Patients will undergo one
      additional day between the two steps of the transplant which may allow their donor's cells to
      fight the disease more effectively.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Any patient with a hematologic malignancy with residual disease after treatment with 1
             or more chemotherapy regimens in whom achievement of remission with additional
             chemoradiotherapy is felt to be unlikely or who is in 3rd or greater complete
             remission (CR).

             Patients with marrow based diseases in which the marrow biopsy does not meet criteria
             for active disease (ie <5% blasts in acute leukemia) but who does not have full count
             recovery will be eligible for treatment on this high risk trial.

          2. Patients must have at least one related donor who is HLA mismatched in the GVHD
             direction at two or more HLA loci.

          3. Patients must adequate organ function:

               1. Left ventricular ejection fraction (LVEF) of >50 %

               2. Diffusion capacity of the lung for carbon monoxide (DLCO) (adjusted for
                  hemoglobin) >50 % of predicted

               3. Adequate liver function as defined by a serum bilirubin <1.8, Aspartate
                  aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 times upper limit
                  of normal

               4. Creatinine clearance of > 60 ml/min

          4. Karnofsky Performance Status of > 80% on the modified KPS tool

          5. Patients must be willing to use contraception if they have childbearing potential.

          6. Able to give informed consent

        Exclusion Criteria:

          1. Modified Karnofsky performance status (KPS) of <80%

          2. > 5 Comorbidity Points on the hematopoietic cell transplantation comorbidity index
             (HCT-CI) Index

          3. Untreated class I or II antibodies against donor HLA antigens

          4. HIV positive

          5. Active involvement of the central nervous system with malignancy

          6. Psychiatric disorder that would preclude patients from signing an informed consent

          7. Pregnancy, or unwillingness to use contraception if they have child bearing potential

          8. Patients with life expectancy of < 6 months for reasons other than their underlying
             hematologic/oncologic disorder

          9. Alemtuzumab treatment within 8 weeks of HSCT admission.

         10. Anti-thymocyte globulin (ATG) level of > 2 ugm/ml

         11. Patients with active inflammatory processes including Tmax >101 or active tissue
             inflammation are excluded

         12. Inability to tolerate cyclophosphamide or undergo total body irradiation at the doses
             specified in the treatment plan