High Dose Cyclophosphamide, Tacrolimus, and Mycophenolate Mofetil in Preventing Graft Versus Host Disease in Patients With Hematological Malignancies Undergoing Myeloablative or Reduced Intensity Donor Stem Cell Transplant
Condition: Acute Leukemia; Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Diffuse Large B-Cell Lymphoma; Follicular Lymphoma; Graft Versus Host Disease; Hodgkin Lymphoma; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Myelodysplastic Syndrome; Myeloproliferative Neoplasm; Recurrent Acute Myeloid Leukemia With Myelodysplasia-Related Changes; Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma; Secondary Myelodysplastic Syndrome
MeSH terms: Lymphoma; Leukemia; Multiple Myeloma; Neoplasms, Plasma Cell; Preleukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myeloid; Lymphoma, Mantle-Cell; Lymphoma, Large B-Cell, Diffuse; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Hematologic Neoplasms; Myelodysplastic Syndromes; Myeloproliferative Disorders; Graft vs Host Disease; Syndrome; Recurrence
Intervention: Busulfan; Cyclophosphamide; Fludarabine Phosphate; Hematopoietic Cell Transplantation; Laboratory Biomarker Analysis; Melphalan Hydrochloride; Mycophenolate Mofetil; Peripheral Blood Stem Cell Transplantation; Quality-of-Life Assessment; Tacrolimus; Total-Body Irradiation
Intervention description: Given IV; Given IV; Given IV; Undergo PBSC HCT; Correlative studies; Given IV; Given IV or PO; Undergo PBSC HCT; Ancillary studies; Given IV; Undergo TBI
Intervention MeSH terms: Mycophenolic Acid; Cyclophosphamide; Melphalan; Busulfan; Fludarabine; Fludarabine phosphate; Tacrolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 38.0
Sex: All
Minimum age: 5 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      This pilot phase II trial studies how well high dose cyclophosphamide, tacrolimus, and
      mycophenolate mofetil work in preventing graft versus host disease in patients with
      hematological malignancies undergoing myeloablative or reduced intensity donor stem cell
      transplant. Sometimes the transplanted cells from a donor can make an immune response against
      the body's normal cells (called graft versus host disease). Giving high dose
      cyclophosphamide, tacrolimus, and mycophenolate mofetil after the transplant may stop this
      from happening.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with acute leukemia or chronic myelogenous leukemia with no circulating
             blasts and with less than 10% blasts in the bone marrow

          -  Patients with myelodysplastic syndrome (MDS) with intermediate-2 or high risk per
             International Prognostic Scoring System (IPSS) (or intermediate, high, very high risk
             by Revised International Prognostic Scoring System [IPSS-R]) or myeloproliferative
             neoplasm; primary or secondary if high-risk features or refractory disease

          -  Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, follicular,
             marginal zone, diffuse large B-cell, Hodgkin lymphoma, or mantle cell lymphoma with
             chemosensitive disease at time of transplantation; all types of lymphoma are eligible

          -  High risk, or refractory and relapsed multiple myeloma

          -  No available human leukocyte antigen (HLA)-matched related donor

          -  Available matched unrelated donor

          -  Ejection fraction at rest >= 50%

          -  Karnofsky performance status (KPS) >= 70

          -  Measured creatinine clearance more than 60 mL/min. The updated Schwartz formula should
             be used for pediatric patients (>=5 to 12 years old)

          -  Carbon monoxide diffusing capability test (DLCO) >= 50% (adjusted for hemoglobin) and
             forced expiratory volume in 1 second (FEV1) >= 50%

          -  Total bilirubin < 1.5 x the upper limit of normal; patients who have been diagnosed
             with Gilbert's disease are allowed to exceed the defined bilirubin value of 1.5 x the
             upper limit of normal

          -  Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) < 2.5 x the upper
             limit of normal

          -  Alkaline phosphatase < 2.5 x the upper limit of normal

          -  Female subjects (unless postmenopausal for at least 1 year before the screening visit,
             or surgically sterilized), agree to practice two (2) effective methods of
             contraception at the same time, or agree to completely abstain from heterosexual
             intercourse, from the time of signing of the informed consent through 12 months
             post-transplant

          -  Male subjects (even if surgically sterilized), of partners of women of childbearing
             potential must agree to one of the following: practice effective barrier
             contraception, or abstain from heterosexual intercourse from the time of signing the
             informed consent through 12 months post-transplant

          -  All subjects must have the ability to understand and the willingness to sign a written
             informed consent document

        DONOR INCLUSION CRITERIA

          -  7 out of 8 at high resolution using deoxyribonucleic acid (DNA)-based typing with
             either antigen or allele mismatched HLA (-A, -B, -C, and -DR) or 8/8 HLA-mismatched
             with either double DQ mismatch (10/12) or combined DQ and DP mismatch

          -  Donor must be willing to donate peripheral blood stem cells

          -  Suitable donor

          -  Medically cleared to donate per National Marrow Donor Program (NMDP)

          -  Absence of donor-specific antibodies (DSA) to the mismatched HLA-locus

          -  Donor choices per matched unrelated donor (MUD) committee according to center standard
             operating procedure (SOP)

        Exclusion Criteria:

          -  Prior allogeneic transplant

          -  Active central nervous system (CNS) involvement by malignant cells

          -  Patients with uncontrolled bacterial, viral or fungal infections (currently taking
             medication and with progression or no clinical improvement) at time of enrollment

          -  Patients with transformed lymphoma (e.g., Richter's transformation arising in
             follicular lymphoma or chronic lymphocytic leukemia)

          -  Patients seropositive for the human immunodeficiency virus (HIV)

          -  Patients with active hepatitis B or C determined by polymerase chain reaction (PCR)

          -  Myocardial infarction within 6 months prior to enrollment or New York Heart
             Association (NYHA) class III or IV heart failure, uncontrolled angina, severe
             uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
             ischemia or active conduction system abnormalities; prior to study entry, any
             electrocardiography (ECG) abnormality at screening must be documented by the
             investigator as not medically relevant

          -  Female patients who are lactating or pregnant

          -  Patients with a serious medical or psychiatric illness likely to interfere with
             participation in this clinical study

          -  History of another primary malignancy that has not been in remission for at least 3
             years (the following are exempt from the 3-year limit: non-melanoma skin cancer, fully
             excised melanoma in situ [Stage 0], curatively treated localized prostate cancer, and
             cervical or breast carcinoma in situ on biopsy or a squamous intraepithelial lesion on
             PAP smear)

          -  Psychosocial issues: no appropriate caregivers identified, or non-compliant to
             medications

          -  Subjects, who in the opinion of the investigator, may not be able to comply with the
             safety monitoring requirements of the study