Multi-Ctr PII Cmb.Modality Tx Ruxolitinib, Decitabine, and DLI for Post HSCT in AML/MDS
Condition: Acute Myeloid Leukemia; Myeloid and Monocytic Leukemia; Myelodysplastic Syndromes
MeSH terms: Leukemia; Myelodysplastic Syndromes
Intervention: Decitabine; Ruxolitinib; Donor Lymphocyte Infusion (DLI)
Intervention description: 10 days of decitabine 20 mg/m2 IV daily; or, alternatively, per institution, physician, or patient preference on a 5-2-5 schedule with no weekend infusion. If a CR is achieved after 2 cycles using the 10-day schedule, subsequent cycles will change to a 5-day schedule.; Starting with day 1 of cycle 1 and continuing for up to 6 months after the end of the last cycle, patients will receive ruxolitinib 5 mg twice daily orally. Dose may be increased to 10 mg twice daily in cycles 2 through 4 if platelets improve to >100 x 10^9/L.; DLI from the original donor will be infused within 10 days after the last dose of decitabine in each cycle.
Intervention MeSH terms: Decitabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No
Keywords: AML; MDS

Summary:

      This is a multi-center, single-arm, open-label, phase II trial for the frontline treatment of
      relapsed AML or MDS following allo-HCT. Eligible subjects will receive up to 4 cycles of
      combined modality treatment. The number of cycles depends on response, toxicity, and the
      remaining cell dose.
    

Eligibility criteria:

        Patient Inclusion Criteria:

          -  Age ≥12 years

          -  Have undergone first allo-HCT from a 6/6 matched sibling donor, 8/8 matched unrelated
             donor, or an HLA haploidentical donor.

          -  History of AML or MDS for which allo-HCT was performed. Overlap MPN/MDS is included.

          -  Untreated relapse of the underlying malignancy as defined by >5% of malignant blasts
             (by morphology and/or flow cytometry) in the bone marrow, or myeloid sarcoma.

          -  Additional cells sufficient for the first DLI available from the same donor, or the
             donor must be willing to donate. Both G-CSF mobilized and unmobilized products are
             allowed and the choice is at the discretion of the treating physician.

          -  Partial (or better) engraftment from the bone marrow showing relapse, defined as >50%
             donor chimerism on non-split RFLP. Patients with chimerism of 25-50% may be enrolled
             with approval of the site PI and Sponsor/Investigator

          -  Karnofsky performance status ≥ 50%

          -  Adequate organ function within 14 days of study registration defined as:

               -  Total bilirubin < 1.5 x upper limit of institutional normal, unless a diagnosis
                  of Gilbert's disease

               -  AST/ALT < 2.5 x upper limit of institutional normal

               -  Creatinine clearance ≥40 mL/minute as calculated by the Cockcroft-Gault formula.
                  Cockcroft-Gault CrCl = (140-age) * (Wt in kg) * (0.85 if female) / (72 * Cr).

          -  Peripheral white blood cell count <50 x 10^9/L. The use of hydroxyurea for
             cytoreduction is allowed and may continue until cycle 2 day 1

          -  Subjects and spouse/partner who are of childbearing potential must be using highly
             effective contraception consisting of 2 forms of birth control (at least 1 of which
             must be a barrier method) starting at Screening and continuing through the entire
             study (for at least 3 months after the last dose of ruxolitinib if study treatment is
             stopped early or subject withdraws consent). Highly effective contraception is defined
             as:

               -  Established use of oral, injected or implanted hormonal methods of contraception.

               -  Placement of an intrauterine device or intrauterine system.

               -  Double barrier methods of contraception: condom or occlusive cap (diaphragm or
                  cervical/vault caps) with spermicidal foam/gel/film/cream/suppository (double
                  barrier method will count as 2 forms of contraception).

          -  Male subjects must not donate sperm during the Screening and Treatment Periods, and
             for at least 3 months after the last dose of ruxolitinib.

          -  Subjects are willing and able to give written informed consent and to comply with all
             study visits and procedures. Parents or legal guardians will consent for minors and
             minors will be asked to assent.

        Patient Exclusion Criteria:

          -  Active uncontrolled infection at the time of consent. An active uncontrolled infection
             is defined as hemodynamic instability attributable to sepsis or new symptoms,
             worsening physical signs or radiographic findings attributable to infection.
             Persisting fever without signs or symptoms of infection will not be interpreted as an
             active uncontrolled infection. Subjects with a controlled infection receiving
             definitive therapy for 72 hours prior to enrollment are eligible.

          -  History of infection with human immunodeficiency virus (HIV), unresolved hepatitis B,
             or hepatitis C.

          -  Untreated CNS leukemia

          -  Untreated or active GVHD (acute or chronic)

          -  History of grade III-IV acute GVHD at any point in time

          -  Any form of iatrogenic immunosuppression except <0.5 mg/kg/day of prednisone or
             equivalent at the time of consent.

          -  Unresolved veno-occlusive disease of the liver, defined as persistent bilirubin
             abnormalities not attributable to GVHD and ongoing organ dysfunction (renal, ascites).

          -  Subjects who are pregnant, breast feeding or sexually active and unwilling to use
             effective birth control for the duration of the study, as agents in this study are in
             pregnancy category C: Animal reproduction studies have shown an adverse effect on the
             fetus and there are no adequate and well-controlled studies in humans, and category D:
             there is positive evidence of human fetal risk based on adverse reaction data from
             investigational or marketing experience or studies in humans.

          -  Radiation therapy within 14 days prior to consent.

          -  Any prior therapy for relapse after allo-HCT.

          -  Prior DLI. CD34-selected boost is allowed

          -  Exposure to any other investigational agent, device or procedure within 14 days prior
             to consent

          -  Patients or donors with any medical or psychological condition that, in the opinion of
             the Investigator, might interfere with the subject's participation in the trial, pose
             any additional risk for the patient/donor, or confounds the assessments of the
             subject.

          -  Subjects with known allergies, hypersensitivity or intolerance to ruxolitinib or
             similar compounds.