Overview
Allogeneic hematopoietic cell transplantation (HCT) is one of the only curative intent therapies available for hematologic malignancies. HLA-matched sibling donors have historically offered the best clinical results but are unavailable for the majority of patients, while most patients do have readily available haploidentical donors. One of the risks of a haploidentical HCT is graft vs. host disease (GVHD), but it is difficult to reduce the incidence of GVHD without compromising the graft vs. leukemia (GVL) effect.
The hypothesis of this study is that JAK inhibition with haploidentical HCT may mitigate GVHD and cytokine release syndrome while retaining the GVL effect and improving engraftment.
Eligibility
Inclusion Criteria:
Patients must meet the following criteria within 30 days prior to Day -3 unless otherwise
noted.
- Diagnosis of one of the hematological malignancies listed below:
- Acute myelogenous leukemia (AML) in complete morphological remission, complete
remission with incomplete hematologic recovery, and complete remission with
partial hematologic recovery (based on ELN Criteria47).
- Acute lymphocytic leukemia (ALL) in complete morphological remission (MRD
negative by flow cytometry with sensitivity to ≤ 10-4).
- Myelodysplastic syndrome with ≤ 10% blasts in bone marrow.
- Non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HD) in second or greater complete
or partial remission.
- Myelofibrosis with ≤ 10% blasts in bone marrow. Up to five patients with
myelofibrosis will be permitted in the expansion phase ONLY.
- Planned treatment is T cell-replete peripheral blood haploidentical donor
transplantation.
- Available HLA-haploidentical donor who meets the following criteria:
- Blood-related family member, including (but not limited to) sibling, offspring,
cousin, nephew, or parent. Younger donors should be prioritized.
- At least 18 years of age.
- HLA-haploidentical donor/recipient match by at least low-resolution typing per
institutional standards.
- In the investigator's opinion, is in general good health and medically able to
tolerate leukapheresis required for harvesting hematopoietic stem cells.
- No active hepatitis.
- Negative for HTLV and HIV.
- Not pregnant.
- Donor selection will be in compliance with FDA guidelines as provided in 21 CFR
1271 for donor eligibility
https://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatory
Information/Guidances/Tissue/UCM091345.pdf
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
- Adequate organ function as defined below:
- Total bilirubin ≤ 1.5 x IULN.
- AST (SGOT) and ALT (SGPT) ≤ 3.0 x IULN.
- Creatinine ≤ 1.5 x IULN OR creatinine clearance ≥ 45 mL/min/1.73 m2 by
Cockcroft-Gault Formula.
- Oxygen saturation ≥ 90% on room air.
- LVEF ≥ 40%.
- FEV1 and FVC ≥ 40% predicted, DLCOc ≥ 40% predicted. If DLCO is < 40%, patients
will still be considered eligible if deemed safe after a pulmonary evaluation.
- Able to receive GVHD prophylaxis with tacrolimus, mycophenolate mofetil, and
cyclophosphamide.
- At least 18 years of age at the time of study registration
- The effects of ruxolitinib on the developing human fetus are unknown. Additionally,
tacrolimus may increase risk of hypertension, preeclampsia, preterm birth, and low
birth weight; and mycophenolate mofetil is considered to be teratogenic. For this
reason, women of childbearing potential and men must agree to use adequate
contraception (hormonal or barrier method of birth control, abstinence) prior to study
entry and for the duration of study participation. Should a woman become pregnant or
suspect she is pregnant while participating in this study, she must inform her
treating physician immediately. Men treated or enrolled on this protocol must also
agree to use adequate contraception prior to the study and for the duration of the
study.
- Able to understand and willing to sign an IRB approved written informed consent
document (or that of legally authorized representative, if applicable).
Exclusion Criteria:
- Prior allogeneic transplant (regardless of whether donor was related, unrelated, or
cord). Prior autologous transplant is not exclusionary.
- Presence of donor specific antibodies (DSA) with Mean Fluorescence Intensity (MFI) of
≥ 2000 as assessed by the single antigen bead assay.
- Known HIV or active hepatitis B or C infection. Known current and/or history of active
tuberculosis.
- Known hypersensitivity to one or more of the study agents.
- Planning to receive antithymocyte globulin as part of the pre-transplant conditioning
regimen.
- Currently receiving or has received any investigational drugs within the 14 days prior
to the first dose of study drug (Day -3).
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative
pregnancy test within 14 days of study entry.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, autoimmune disease, symptomatic congestive heart failure, unstable angina
pectoris, or unstable cardiac arrhythmias.
- Immunosuppressive doses of steroids. Subjects with steroids for adrenal insufficiency
will not be excluded.