Clinical trial NCT02208037 (phase 2, status: completed)
Conditions: acute leukemia, chronic myelogenous leukemia, myelodysplasia, chronic lymphocytic leukemia, small lymphocytic lymphoma, lymphoma, b-cell, lymphoma, follicular, lymphoma, large b-cell, diffuse, hodgkin's lymphoma
ICD codes: C91.01, C91.02, C92.01, C92.02, C92.41, C92.42, C92.51, C95.91, C95.92, Z80.6, Z85.6, C90.11, C90.12, C91.01, C91.11, C91.12, C91.10, S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S, S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S, S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S, S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S, S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S
Drugs: tacrolimus (arm with methotrexate), tacrolimus (arm with mmf and cyclophosphamide), methotrexate (arm with maraviroc), methotrexate (arm with bortezomib), maraviroc, bortezomib, mycophenolate mofetil, cyclophosphamide
SMILES: CO[C@@H]1C[C@@H](CC[C@H]1O)\C=C(/C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@]2(O)O[C@@H]([C@H](C[C@H]2C)OC)[C@H](C[C@@H](C)C\C(C)=C\[C@@H](CC=C)C(=O)C[C@H](O)[C@H]1C)OC, ClCCN(CCCl)P1(=O)NCCCO1, CN(CC1=CN=C2N=C(N)N=C(N)C2=N1)C1=CC=C(C=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O, CN(CC1=CN=C2N=C(N)N=C(N)C2=N1)C1=CC=C(C=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O, CC(C)C1=NN=C(C)N1[C@H]1C[C@@H]2CC[C@H](C1)N2CC[C@H](NC(=O)C1CCC(F)(F)CC1)C1=CC=CC=C1, ClCCN(CCCl)P1(=O)NCCCO1, N[C@@H](CCCNC(N)=N)C(O)=O, ClCCN(CCCl)P1(=O)NCCCO1
Eligibility criteria:

        Inclusion Criteria:

          1. Age 18-75 years (patient is older than 18.0 and less than 76.0 years old)

          2. Patients with acute leukemia, chronic myelogenous leukemia or myelodysplasia with no
             circulating blasts and with less than 5% blasts in the bone marrow.

          3. Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, follicular,
             marginal zone, diffuse large B-cell, Hodgkin's Lymphoma,or mantle cell lymphoma with
             chemosensitive disease at time of transplantation

          4. Planned reduced intensity conditioning regimen (see eligible regimens in Table 2.4a)

          5. Patients must have a related or unrelated peripheral blood stem cell donor as follows:

               1. Sibling donor must be a 6/6 match for HLA-A and -B at intermediate (or higher)
                  resolution, and -DRB1 at high resolution using DNA-based typing, and must be
                  willing to donate peripheral blood stem cells and meet institutional criteria for
                  donation.

               2. Unrelated donor must be a 7/8 or 8/8 match at HLA-A, -B, -C and -DRB1 at high
                  resolution using DNA-based typing. Unrelated donor must be willing to donate
                  peripheral blood stem cells and be medically cleared to donate stem cells
                  according to National Marrow Donor Program (NMDP) criteria.

          6. Cardiac function: Ejection fraction at rest ≥ 45%

          7. Estimated creatinine clearance greater than 50 mL/minute (using the Cockcroft-Gault
             formula and actual body weight)

          8. Pulmonary function: Diffusing capacity of the lung for carbon monoxide (DLCO) ≥ 40%
             (adjusted for hemoglobin) and forced expiratory volume in one second (FEV1) ≥ 50%

          9. Liver function: total bilirubin < 1.5 x the upper limit of normal and alanine
             aminotransferase (ALT)/aspartate aminotransferase (AST) < 2.5x the upper normal limit.
             Patients who have been diagnosed with Gilbert's Disease are allowed to exceed the
             defined bilirubin value of 1.5x the upper limit of normal.

         10. 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 the informed consent through 12 months post
             transplant (see Section 2.6.4 for definition of postmenopausal).

         11. Male subjects (even if surgically sterilized), of partners of women of childbearing
             potential must agree to one of the following: practice effective barrier contraception
             (see Section 2.6.4 for list of barrier methods), or abstain from heterosexual
             intercourse from the time of signing the informed consent through 12 months post
             transplant.

         12. Signed informed consent

        Exclusion Criteria:

          1. Prior allogeneic transplant

          2. Karnofsky Performance Score < 70%

          3. Active central nervous system (CNS) involvement by malignant cells

          4. Patients with uncontrolled bacterial, viral or fungal infections (currently taking
             medication and with progression or no clinical improvement) at time of enrollment.

          5. Presence of fluid collection (ascites, pleural or pericardial effusion) that
             interferes with methotrexate clearance or makes methotrexate use contraindicated

          6. Patients with transformed lymphoma (e.g., Richters transformation arising in
             follicular lymphoma or chronic lymphocytic leukemia)

          7. Patients seropositive for the human immunodeficiency virus (HIV)

          8. Patient with active Hepatitis B or C determined by serology and/or nucleic acid
             amplification tests (NAAT)

          9. Patients with hypersensitivity to bortezomib, boron or mannitol

         10. Patients with ≥ grade 2 sensory peripheral neuropathy

         11. Myocardial infarction within 6 months prior to enrollment or New York Heart
             Association (NYHA) Class III or IV heart failure (see Appendix D), uncontrolled
             angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence
             of acute ischemia or active conduction system abnormalities. Prior to study entry, any
             ECG abnormality at screening must be documented by the investigator as not medically
             relevant.

         12. Female patients who are lactating or pregnant

         13. Patients with a serious medical or psychiatric illness likely to interfere with
             participation in this clinical study

         14. Patients with prior malignancies except resected basal cell carcinoma or treated
             cervical carcinoma in situ. Cancer treated with curative intent ≥ 5 years previously
             will be allowed. Cancer treated with curative intent < 5 years previously will not be
             allowed unless approved by the Protocol Officer or one of the Protocol Chairs.

         15. Planned use of anti-thymocyte globulin (ATG) or alemtuzumab in conditioning regimen.

         16. Planned post-transplant therapy, including use of tyrosine-kinase inhibitors (TKI).

         17. Inability to withhold agents that may interact with hepatic cytochrome P450 enzymes
             (CYP3A4), or glutathione S-transferases involved in bortezomib and/or busulfan
             metabolism during day -5 through day +7. It is acceptable to use alternative
             non-interacting medications during this period, and then resume prior medications.

         18. Patients with secondary acute myeloid leukemia arising from myeloproliferative
             disease, including Chronic myelomonocytic leukemia (CMML), with evidence of active
             myeloproliferative features or myelofibrosis in the background.