Very Low Dose Total Body Irradiation, Total Lymphoid Irradiation, and Anti-Thymocyte Globulin in Treating Patients Undergoing Donor Stem Cell Transplant

Status: Active

Description

This phase II trial studies how well very low dose total body irradiation, total lymphoid irradiation, and anti-thymocyte globulin work in treating patients undergoing donor stem cell transplant. Giving radiation therapy before a donor stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient, they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes, the transplanted cells from a donor can make an immune response against the body's normal cells called graft versus host disease. Giving anti-thymocyte globulin may help stop this from happening.

Eligibility Criteria

Inclusion Criteria

  • Has a human leukocyte antigen (HLA)-matched or single allele-mismatched adult sibling donor or unrelated donor.
  • Has a myeloid or lymphoid malignant disease that is treated with TLI and ATG reduced-intensity conditioning for allogeneic transplant (any of the following: acute myeloid leukemia [AML]; myelodysplastic syndrome [MDS]; myeloproliferative disease syndrome [MPD]); chronic lymphocytic leukemia (CLL); B or T-cell non-Hodgkin lymphoma (NHL); Hodgkin lymphoma (HL); or chronic myelomonocytic leukemia (CMML).
  • Patients who due to age, pre-existing medical conditions, or, prior therapy are considered to be at high-risk for regimen-related toxicity associated with fully ablative transplant conditioning, and therefore reduced intensity conditioning is recommended.
  • Ability to understand and the willingness to sign a written informed consent document. Patients must have signed informed consent to participate in the trial.

Exclusion Criteria

  • Uncontrolled bacterial, viral or fungal infection defined as currently taking medication and progression of clinical symptoms.
  • Progressive hemato-lymphoid malignancy despite conventional therapy.
  • Chronic myelogenous leukemia (CML).
  • Active central nervous system (CNS) involvement of the underlying malignancy.
  • Human immunodeficiency virus (HIV)-positive.
  • Pregnant or lactating.
  • Prior malignancy (EXCEPTION: diagnosed > 5 years ago without evidence of disease, OR treated =< 5 years ago but have a greater than 50% chance of life expectancy of >= 5 years for that malignancy).
  • Have a psychiatric disorder(s) or psychosocial circumstance(s) which in the opinion of the primary physician would place the patient at an unacceptable risk from transplant.
  • Left ventricular ejection fraction (LVEF) < 30%, or uncontrolled cardiac failure.
  • Diffusing capacity of lung for carbon monoxide (DLCO) < 40% predicted.
  • Total bilirubin > 3 mg/dL.
  • Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) > 4 x upper limit of normal (ULN).
  • Creatinine > 2 mg/dL and an estimated creatinine clearance < 40 mL/min.
  • Poorly controlled hypertension despite multiple antihypertensive medications.
  • Karnofsky performance status (KPS) < 60%.

Locations & Contacts

California

Palo Alto
Stanford Cancer Institute Palo Alto
Status: Active
Contact: Robert Lowsky
Phone: 650-723-0822
Email: rlowsky@stanford.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine the proportion of patients with full donor T-cell chimerism at day 28 following hematopoietic cell transplantation.

SECONDARY OBJECTIVES:

I. To determine the risk of disease progression, overall and event free survival, and non-relapse mortality, following treatment with total lymphoid irradiation (TLI)/anti-thymocyte globulin (ATG)/total body irradiation (TBI).

II. To determine the incidence of acute and chronic graft-versus-host disease (GVHD) following treatment with TLI/ATG/TBI.

EXPLORATORY OBJECTIVES:

I. To determine the changes in frequency of hematopoietic stem, progenitor, and mature cell subsets and the changes in cytokine milieu and cellular architecture in the bone marrow of patients receiving TLI compared to TLI+TBI.

OUTLINE:

Patients undergo TLI on days -11 to -7 and on days -4 to -1, receive ATG intravenously (IV) on days -11 to -7, receive tacrolimus orally (PO) twice daily (BID) or IV beginning on day -4, and undergo TBI on day -1. Patients then undergo allogeneic hematopoietic cell transplantation on day 0 and receive mycophenolate mofetil PO BID for matched related donors or PO every 8 hours (Q8H) for unrelated donors (URDs) or mismatched related donors beginning on day 0.

After completion of study treatment, patients are followed up at days 28, 56, and 90, 180, and 360.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Stanford Cancer Institute Palo Alto

Principal Investigator
Robert Lowsky

Trial IDs

Primary ID BMT330
Secondary IDs NCI-2018-02703
Clinicaltrials.gov ID NCT03734601