Haplo Peripheral Blood Sct In GVHD Prevention

Reduced Intensity Haploidentical Peripheral Blood Stem Cell Transplantation With Post-transplant Cyclophosphamide and Sirolimus/Mycophenolate Mofetil/RGI-2001 Based GVHD Prevention: a Pilot Study

This research study is studying the RGI-2001 for preventing Graft-vs-Host Disease (GVHD) in people with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), myelodysplastic syndrome (MDS), myeloproliferative disorders (MPN), chronic myelomonocytic leukemic (CMML), chemosensitive hodgkin lymphoma (HL), or Non-Hodgkin lymphoma (NHL).who will have a blood stem cell transplantation.

• GVHD is a condition in which cells from the donor's tissue attack the organs.
• RGI-2001 is an investigational treatment

• This is a pilot study in subjects undergoing reduced-intensity haploidentical peripheral blood stem cell transplantation who will receive graft-versus-host disease prevention with post-transplant cyclophosphamide, followed by sirolimus, mycophenolate mofetil, and RGI-2001.

• The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.

• The standard of care drugs of fludarabine, cyclophosphamide, melphalan, radiation, sirolimus, and mycophenolate mofetil are all FDA approved.

  • Eligible Participants will be placed in 1 of 2 groups, per physicians discretion:

  • Regimen #1 :

    • Before stem cell transplant:Fludarabine + Cyclophosphamide + Radiation
    • After stem cell transplant: Cyclophosphamide + Sirolimus +Mycophenolate mofetil + RGI-2001

  • Regimen #2

    • Before stem cell transplant: fludarabine + melphalan + radiation
    • After stem cell transplant: cyclophosphamide + sirolimus +Mycophenolate mofetil + RGI-2001

• A total of 20 participants will be enrolled to this trial

• The U.S. Food and Drug Administration (FDA) has not approved RGI-2001 as a treatment for any disease.

Inclusion Criteria:

• Men or women ≥ 18 and ≤ 80 years old

• Diagnosis of hematological malignancy:

  • Acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) in morphologic complete remission
  • Myelodysplastic syndrome (MDS), myeloproliferative disorders (MPN), or chronic myelomonocytic leukemic (CMML) with < 5% blasts in blood or bone marrow
  • Chemosensitive Hodgkin lymphoma (HL) or Non-Hodgkin lymphoma (NHL)

• Patients must be undergoing haploidentical allogeneic hematopoietic cell transplantation, defined as 1st or 2nd degree relative with at least 5/10 matching at HLA-A, -B, -C, DR, and DQ.

• ECOG performance status ≤2

• Patients with adequate physical function as measured by:

  • Cardiac: Left ventricular ejection fraction at rest must be ≥ 40%, or shortening fraction >25%

  • Hepatic:

    • Bilirubin ≤ 2.5 mg/dL, except for patients with Gilbert's syndrome or hemolysis
    • ALT, AST, and Alkaline Phosphatase < 5 x ULN

  • Renal: Serum creatinine within normal range, or if serum creatinine is outside normal range, then renal function (measured or estimated creatinine clearance or GFR) ≥ 40mL/min/1.73m2

  • Pulmonary: DLCO (corrected for hemoglobin), FEV1 and FVC ≥ 50% predicted

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Prior allogeneic hematopoietic stem cell transplantation. (Patients may have received a prior autologous hematopoietic stem cell transplant.)
• Participants who are receiving any other investigational agents within 14 days prior to RGI-2001 dosing. Thus, participants must stop investigational agents by Day -9 prior to transplant.
• Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, recent myocardial infarction or stroke, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients with active or uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
• Planned use of prophylactic donor lymphocyte infusion (DLI) therapy.
• Pregnant and breast-feeding women are ineligible because they are not eligible for hematopoietic stem cell transplantation.
• HIV-positive participants and patients with active Hepatitis B or C are ineligible