Philadelphia, Pennsylvania 19107


Purpose:

This clinical trial studies the use of reduced intensity chemotherapy and radiation therapy before donor stem cell transplant in treating patients with hematologic malignancies. Giving low doses of chemotherapy, such as cyclophosphamide and fludarabine phosphate, before a donor stem cell transplant may help stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Reducing the intensity of the chemotherapy and radiation may also reduce the side effects of the donor stem cell transplant.


Study summary:

PRIMARY OBJECTIVES: I. To demonstrate efficacy of this approach over the historical 2 step reduced intensity conditioning (RIC) approaches in the "vulnerable" population defined as: patients with hematopoietic cell transplant (HCT)-co-morbidity index (CI)/age scores >= 2, but no more than a score of 5 as based on the Sorror et al. data. SECONDARY OBJECTIVES: I. To compare the non-relapse mortality (NRM) and relapse related mortality (RRM) rates at 1 year for patients treated on this study to the that of patients undergoing haploidentical RIC hematopoietic stem cell transplantation (HSCT) as reported in the literature and as observed in the 2 step RIC trials. II. To determine the incidence and severity of graft-versus-host disease (GVHD) in patients undergoing treated on the Thomas Jefferson University (TJU) RIC 2 step approach. III. To evaluate engraftment rates and lymphoid reconstitution in patients treated on the TJU RIC 2 step approach. OUTLINE: RIC: Patients receive fludarabine phosphate intravenously (IV) over 60 minutes on days -10 to -8 and cyclophosphamide IV over 2 hours on days -3 and -2. Patients also undergo total body irradiation (TBI) followed by a donor lymphocyte infusion (DLI) on day -6. TRANSPLANT: Patients undergo cluster of differentiation (CD)34+ peripheral blood stem cell transplant on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus orally (PO) beginning day -1 with a taper initiated on day 42 and mycophenolate mofetil IV twice daily (BID) on days -1 to 28 in the absence of GVHD. After completion of study treatment, patients are followed up for 1 year.


Criteria:

Inclusion Criteria: 1. Patients treated on this study will have: 1. Acute myeloid leukemia in morphologic CR not requiring treatment for their disease for 6 weeks 2. A history of AML with < 20% residual blasts after induction therapy and persisting with <20% blasts for at least 8 weeks without reinduction. 3. RA or RARS or isolated 5q- can proceed to transplant without any treatment 4. RAEB-1, RCMD+/-RS, or MDS NOS with stable disease for 6 months (as documented by serial bone marrow examinations) in the absence of any therapy but growth factors or transfusion support. Patients who require treatment to "control their disease" must show chemo-responsiveness 5. CMML or RAEB-2 must demonstrate chemo-responsiveness. Chemo-responsiveness is defined as a blast percentage decrease by at least 5 percentage points and there must be less than 20% blasts after treatment and at the time of transplant 6. Hodgkin or Indolent Non-Hodgkin's lymphoma 7. Myeloma with < 5% plasma cells in the marrow 8. Myeloproliferative disorders 9. Aplastic Anemia 10. A hematological or oncological disease (not listed) in which allogeneic HSCT is thought to be beneficial, and the disease is chemoresponsive. 11. Patients without clear manifestation of their disease status in terms of stage and/or responsiveness should be discussed with the PI and enrollment analysis should be documented in the study records. 2. Patients must have a related donor who is HLA mismatched at 2, 3, or 4 antigens at the HLA-A; B; C; DR loci in the GVHD direction. (Patients with related donors who are HLA identical or are a 1-antigen mismatch may be treated on this therapeutic approach, but will have their outcomes will not be part of the statistical aims of the study (see Statistical Section). The HLA matched related category includes patients with a syngeneic donor. 3. Patients must have had front line therapy for their disease. 4. Patients must adequate organ function: 1. LVEF (Left ventricular end diastolic function) of >/=45%. 2. DLCO (Diffusing Capacity of the Lung for Carbon Monoxide ) ≥45% of predicted corrected for hemoglobin, FEV-1 (forced expiratory volume at 1 second ≥50% of predicted 3. Adequate liver function as defined by a serum bilirubin <1.8, AST or ALT < 2.5X upper limit of normal 4. Creatinine Clearance of ≥ 60 mL/min 5. HCT-CI/Age Score ≤ 5 points (Patients with greater than 5 points will be allowed for trial with approval of the PI and the Co-PI or his designee. 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. 6. KPS≥ 90% patients older than 70 years, KPS≥ 80% patients younger than 70 years 7. Patients must be willing to use contraception if they have childbearing potential Exclusion Criteria: 1. Performance status < 90% in patients 70 years old or greater, <80% in patients less than age 70 years 2. HCT-CI/age Score >5 points (Patients with greater than 5 points will be allowed for trial with approval of the Principal Investigator and the Co-Principal Investigator or his designee. 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. 3. A diagnosis of CMML, unless in morphologic CR 4. HIV positive 5. Active involvement of the central nervous system with malignancy 6. Inability to obtain informed consent from patient or surrogate 7. Pregnancy 8. Patients with life expectancy of < 6 months for reasons other than their underlying hematologic/oncologic disorder 9. Patients who have received alemtuzumab or antithymocyte globulin within 8 weeks of the transplant admission. The absence of these therapies in the medical record will serve as documentation that they were not given. 10. Patients with evidence of another malignancy, exclusive of a skin cancer that requires only local treatment, should not be enrolled on this protocol


NCT ID:

NCT02566304


Primary Contact:

Principal Investigator
Dolores Grosso, DNP, CRNP
Thomas Jefferson University

Dolores Grosso, DNP, CRNP
Phone: 215-955-8874


Backup Contact:

N/A


Location Contact:

Philadelphia, Pennsylvania 19107
United States

Dolores Grosso, DNP, CRNP
Phone: 215-955-8874

Site Status: Recruiting


Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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