Microtransplantation to Treat Refractory or Relapsed Hematologic Malignancies in Younger Patients
Condition: Acute Myeloid Leukemia (AML); Myelodysplastic Syndrome (MDS)
MeSH terms: Leukemia, Myeloid, Acute; Preleukemia; Hematologic Neoplasms; Myelodysplastic Syndromes
Intervention: Cytarabine; Intrathecal Triples; HPC-A
Intervention description: Given by either intrathecal (IT) or intravenous (IV) route.; given IT.; Given IV.
Intervention MeSH terms: Cytarabine; Hydrocortisone; Methotrexate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: All
Maximum age: 21 Years
Healthy volunteers: No
Keywords: Adolescent; Children; Microtransplant; Leukemia

Summary:

      Allogeneic transplant can sometimes be an effective treatment for leukemia. In a traditional
      allogeneic transplant, patients receive very high doses of chemotherapy and/or radiation
      therapy, followed by an infusion of their donor's bone marrow or blood stem cells. The
      high-dose chemotherapy drugs and radiation are given to remove the leukemia cells in the
      body. The infusion of the donor's bone marrow or blood stem cells is given to replace the
      diseased bone marrow destroyed by the chemotherapy and/or radiation therapy. However, there
      are risks associated with allogeneic transplant. Many people have life-threatening or even
      fatal complications, like severe infections and a condition called graft-versus-host disease,
      which is caused when cells from the donor attack the normal tissue of the transplant patient.

      Recently, several hospitals around the world have been using a different type of allogeneic
      transplant called a microtransplant. In this type of transplant, the donor is usually a
      family member who is not an exact match. In a microtransplant, leukemia patients get lower
      doses of chemotherapy than are used in traditional allogeneic transplants. The chemotherapy
      is followed by an infusion of their donor's peripheral blood stem cells. The objective of the
      microtransplant is to suppress the bone marrow by giving just enough chemotherapy to allow
      the donor cells to temporarily engraft (implant), but only at very low levels. The hope is
      that the donor cells will cause the body to mount an immunologic attack against the leukemia,
      generating a response called the "graft-versus-leukemia" effect or "graft-versus-cancer"
      effect, without causing the potentially serious complication of graft-versus-host disease.

      With this research study, the investigators hope to find out whether or not
      microtransplantation will be a safe and effective treatment for children, adolescents and
      young adults with relapsed or refractory hematologic malignancies
    

Eligibility criteria:

        INCLUSION CRITERIA - AML and MDS PARTICIPANTS

          -  Participants must have a diagnosis of AML or myelodysplastic syndrome (MDS), ALL, and
             must have disease that has relapsed or is refractory to chemotherapy, or that has
             relapsed after HSCT.

               -  Refractory disease is defined as persistent disease after at least two courses of
                  induction chemotherapy.

               -  Patients with AML must have ≥ 5% leukemic blasts in the bone marrow or have
                  converted from negative minimal residual disease (MRD) status to positive MRD
                  status in the bone marrow as assessed by flow cytometry. If an adequate bone
                  marrow sample cannot be obtained, patients may be enrolled if there is
                  unequivocal evidence of leukemia in the peripheral blood.

          -  Participant is ≤ 21 years of age (i.e., has not reached 22nd birthday).

          -  Adequate organ function defined as the following:

               -  Total bilirubin ≤ upper limit of normal (ULN) for age, or if total bilirubin is >
                  ULN, direct bilirubin is ≤ 1.5 mg/dL

               -  AST (SGOT)/ALT (SGPT) < 5 x ULN

               -  Calculated creatinine clearance > 50 ml/min/1.73m^2 as calculated by the Schwartz
                  formula for estimated glomerular filtration rate >

               -  Left ventricular ejection fraction ≥ 40% or shortening fraction ≥ 25%.

          -  Has an available HPC-A donor.

          -  Performance status: Lansky ≥ 50 for patients who are ≤ 16 years old and Karnofsky ≥
             50% for patients who are > 16 years old.

          -  Does not have an uncontrolled infection requiring parenteral antibiotics, antivirals,
             or antifungals within one week prior to first dose. Infections controlled on
             concurrent anti-microbial agents are acceptable, and anti-microbial prophylaxis per
             institutional guidelines is acceptable.

          -  Patient has fully recovered from the acute effects of all prior therapy and must meet
             the following criteria.

               -  At least 14 days must have elapsed since the completion of myelosuppressive
                  therapy.

               -  At least 24 hours must have elapsed since the completion of hydroxyurea, low-dose
                  cytarabine (up to 200 mg/m^2/day), and intrathecal chemotherapy.

               -  At least 30 days must have elapsed since the use of investigational agents.

               -  For patients who have received prior HSCT, there can be no evidence of GVHD and
                  greater than 60 days must have elapsed since the HSCT. Patients cannot be
                  receiving therapy, including steroids, for GVHD.

          -  Post-menarchal female has had negative serum pregnancy test within 7 days prior to
             enrollment.

          -  Male or female of reproductive potential has agreed to use effective contraception for
             the duration of study participation.

          -  Not breastfeeding

        INCLUSION CRITERIA - HPC-A CELL DONOR

          -  At least 18 years of age.

          -  Family member (first degree relatives).

          -  Not pregnant as confirmed by negative serum or urine pregnancy test within 7 days
             prior to enrollment (if female).

          -  Not breast feeding.

          -  Meets donation eligibility requirements as outlined by 21 CFR 1271.