Microtransplantation to Treat Refractory or Relapsed Hematologic Malignancies in Younger Patients

• Status: Terminated
• Trial end date: 2017-05-08
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: St. Jude Children's Research Hospital
• Collaborator: Cookies for Kids' Cancer
• Treatments: Cytarabine; Hydrocortisone; Methotrexate

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.