Donor Stem Cell Transplant in Treating Younger Patients with Hematologic Malignancies or Myelodysplasia

Status: Active

Description

This phase I / II trial studies how well stem cell transplant from partially matched related donors works in treating younger patients with hematologic malignancies or myelodysplasia. Donor stem cell transplant is a procedure in which a patient receives blood-forming stem cells (cells from which all blood cells develop) from a genetically similar, but not identical, donor. Ideally, patients undergoing donor stem cell transplant receive a stem cell graft from a matched sibling; however, less than 30% of patients will have such a donor. There is a high likelihood of being unable to identify a perfect matched unrelated donor. Stem cell transplant from a partially matched related donor may result in result in successful engraftment and rapid immune rebuilding while maintaining a low risk of graft versus host disease.

Eligibility Criteria

Inclusion Criteria

  • ALL in complete remission (CR) >= 2 or high risk disease in CR1 as classified by current Children's Oncology Group (COG) disease protocol. Marrow must be in morphologic remission (minimal residual disease [MRD] positive [+] acceptable)
  • NHL in CR >= 2. Marrow in morphologic remission if applicable (e.g. Burkitt’s leukemia/lymphoma)
  • AML in CR1 if high risk by classification, MRD+ at the end of induction I, or CR >= 2. Bone marrow may show CR (< 5% blasts) or, if chemotherapy refractory disease, < 25% morphologic blasts (M2 marrow). Both primary and secondary AML are eligible
  • Chronic myelogenous leukemia (CML) in chronic phase, accelerated phase, second chronic phase after blast crisis (active blast crisis will not be eligible)
  • Myelodysplastic syndrome
  • Disease recurrence status post first hematopoietic cell transplant (HCT) (eligible for second HCT)
  • Patient lacks an HLA matched sibling donor and a HLA A- B- CDR - DQ- matched unrelated donor is not identified within 30 days of the first confirmatory typing request
  • Meets criteria nonhematopoietic organ function according to Nationwide Children's Hospital (NCH) bone marrow transplant (BMT) standard operating procedures (SOP) 09
  • High resolution HLA and KIR typing
  • The subject cannot have an active untreated infection. Viremia by polymerase chain reaction (PCR) analysis is not considered an active infection but may require immediate viral prophylaxis. Patients with possible fungal infections must have had at least 2 weeks of appropriate anti-fungal therapy and be asymptomatic
  • Negative pregnancy test for females >= 11 years of age or post-menarche
  • Signed consent by parent/guardian and assent if appropriate for subjects < 18 years of age. Signed consent by patient/subject if >= 18 years of age
  • DONOR: The donor must be >= 18 years of age at the time of the informed consent conference
  • DONOR: The donor must be a parent or other related donor
  • DONOR: The donor will be evaluated according to NCH BMT SOP 04 and must meet all criteria
  • DONOR: The donor must be able and willing to undergo G-CSF mobilization and stem cell apheresis
  • DONOR: The patient does not have donor specific anti-HLA antibodies

Exclusion Criteria

  • Patient does not have a suitable donor who is willing and able (meets donor criteria)
  • Patient has donor-specific anti-HLA antibodies

Locations & Contacts

Ohio

Columbus
Nationwide Children's Hospital
Status: Active
Contact: Rolla Abu-Arja
Phone: 614-722-3582
Email: rolla.abu-arja@nationwidechildrens.org

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To estimate the kinetics of neutrophil and platelet engraftment in patients undergoing partially matched related donor hematopoietic cell transplantation with an alpha-beta T cell/CD19+ B cell depleted graft.

II. To estimate the incidence of acute and chronic graft versus host disease (GVHD) in in patients undergoing partially matched related donor hematopoietic cell transplantation with an alpha-beta T cell/CD19+ B cell depleted graft.

III. To estimate the kinetics of immune reconstitution in patients undergoing partially matched related donor hematopoietic cell transplantation with an alpha-beta T cell/CD19+ B cell depleted graft.

SECONDARY OBJECTIVES:

I. To estimate the overall survival, and relapse rate/disease free survival in patients undergoing partially matched related donor hematopoietic cell transplantation with an alpha-beta T cell/CD19+ B cell depleted graft.

II. To characterize the nonhematopoietic regimen related toxicity associated with partially matched related donor hematopoietic cell transplantation with an alpha-beta T cell/CD19+ B cell depleted graft.

OUTLINE:

PREPARATIVE REGIMEN:

Patients with acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL) undergo standard of care total body radiation therapy on days -8 to -6 and receive rabbit anti-thymocyte globulin intravenously (IV) on days -5 to -3, cyclophosphamide on days -4 and -3, and rituximab on day -1.

Patients with acute myeloid leukemia (AML), chronic myelogenous leukemia (CML), and myelodysplastic syndrome receive standard of care busulfan IV on days -11 to -7, thiotepa on day -6, rabbit anti-thymocyte globulin on days -5 to -3, cyclophosphamide on days -5 to -2, and rituximab on day -1. Patients with recurrent disease receive fludarabine on days -8 to -4, rabbit anti-thymocyte globulin IV on days -5 to -3, thiotepa on day -3, melphalan on day -2, and rituximab on day -1.

TRANSPLANT: Patients undergo donor stem cell transplant on day 0. Beginning day 5, patients receive granulocyte colony-stimulating factor daily and continue until absolute neutrophil count > 2000 for 2 days. Patients with recurrent disease after first donor stem cell transplant may undergo a second donor stem cell transplant.

After completion of study treatment, patients are followed up weekly until day 100, monthly for 1 year, and then every 3 months for up to 2 years.

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type

Treatment

Lead Organization

Lead Organization
Nationwide Children's Hospital

Principal Investigator
Rolla Abu-Arja

Trial IDs

Primary ID NCH-16003
Secondary IDs NCI-2019-04919, MOD00001046
Clinicaltrials.gov ID NCT03431090