Background:
People living with HIV(PLWH) are at a higher risk for cancers that may be curable with a bone marrow transplant. HIV infection itself is no longer a reason to not get a transplant, for patients who otherwise have a standard reason to need transplant.
Objective:
This study is being done to see if a new combination of drugs (cyclophosphamide, maraviroc, and bortezomib) is both safe and effective at protecting against graft-versus-host disease after bone marrow transplant. The study will also test the transplant s impact on your survival and control of your cancer.
Eligibility:
People aged 18 years and older living with HIV and a blood cancer that is eligible for a transplant. Healthy family members aged 12 or older who are half matched to transplant recipients are also needed to donate bone marrow.
Design:
The study will be done in 2 phases. The first phase will be to see if we can safely use a new combination of drugs to prevent GVHD. If the combination is safe in the first phase, the study will proceed to the second phase. In the second phase, we will see if this new combination can better protect against GVHD after transplant.
Participants will be screened. Their diagnoses, organ function and eligibility will be confirmed.
Participants will have a catheter inserted into a vein in their chest or neck. Medications and transfusions will be given through the catheter; blood will be drawn from it.
Participants will be in the hospital for 6 weeks or longer.
They will receive various drugs for 2 weeks to prep their body for the transplant.
The transplant cells will be administered through the catheter.
Participants will continue to receive drug treatments after the transplant.
Blood transfusions may also be needed.
Participants will return 1-2 times per week for follow-up visits for 3 months after discharge.
Participants will have visits 6, 12, 18, 24 months after transplant, then once a year for 5 years.
Acute myeloid leukemia in morphologic complete remission (<5% blasts in the bone marrow, no detectable abnormal peripheral blasts, and no extramedullary disease)
Any secondary and/or treatment related myeloid neoplasm with antecedent history of myeloid neoplasm or previous chemotherapy/radiation
B-cell acute lymphoblastic leukemia in first or subsequent complete remission
T-cell acute lymphoblastic leukemia in first or subsequent complete remission
Participants who are receiving any other investigational agents that cannot be discontinued/completed at least 2 weeks prior to the date of beginning conditioning.
Leukemia not having achieved morphologic remission (i.e. bone marrow blasts >5 percent or active extramedullary disease)
Lymphoma not having demonstrated some degree of treatment sensitivity (chemosensitivity, radiosensitivity) by clinical and/or radiologic assessment
Multiple myeloma not in complete remission, as determined by negative immunofixation in serum and urine and disappearance of any soft tissue plasmacytomas and <= 5 percent plasma cells in the bone marrow.
Parallel
RIC
Druge-ATG 40 mg/kg/day IV on days -14 and -13. Prednisone tapering doses given orally daily: -days -14 through -12: 1mg/kg/day -days -11 and -10: 0.75 mg/kg/day -days -9 and -9: 050 mg/kg/day -day -7: 0.25 mg/kg/day Pentostatin 4 mg/m2/day IV on days -11 and -7. Cyclophosphamide 5 mg/kg orally or IV daily on days -11 through -4. Busulfan IV AUC targeted dose of 14.8-23.0 mg\*h/L, on days -3 and -2.
GVHD prophylaxis
DrugCyclophosphamide 50 mg/kg IV daily Bortezomib 1.3 mg/m2 IV +6 hours and +72 hours after graft infusion Mesna 50 mg/kg IV concomitant with cyclophosphamide
allo HCT
Procedure/Surgerybone marrow transplant
Plerixafor
DrugIn phase 1 dose level 3 and phase 2 only: Plerixafor 240 (Micro)g/kg subcutaneously every other day, starting day +1 through day +21
Maraviroc
DrugPhase 1 dose level 2: 300 mg orally twice daily starting day-3 through day day+30
In phase II, avoidance rate of grade III-IV acute GVHD at day +100
Proportion of evaluable recipients who experience grade III-IV acute GVHD at day +100 will be reported along with 80% and 95% two-sided confidence interval
Determine a safe and recommended phase II dose level regimen
Number and type of toxicities noted for participants who are evaluable
Cumulative incidence of primary and secondary graft failure
Cumulative incidence of primary and secondary graft failure based on chimerism at day +100 and 1 year post transplant
Cumulative incidence of hematopoietic recovery
cumulative incidence of hematopoietic recovery will be based on platelet recover at day +100
Overall Survival
Time from transplant to death of any cause and will be determined using the Kaplan-Meier method
Cumulative incidence of relapse
Cumulative incidence rates will be estimated based on disease-risk index.
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