Donor T Cell Depletion in Preventing Graft Versus Host Disease in Patients with Blood Cancer Undergoing a Donor Stem Cell Transplant

Status: Active

Description

This phase II trial studies donor T cell depletion in preventing graft versus host disease (GVHD) in patients with blood cancer undergoing a donor stem cell transplant. Donor stem cell transplants, especially in the mismatched donor setting, are associated with increased risk for GVHD, a condition where the transplanted donor white blood cells attack your body’s normal tissues. Using a cell separation device may remove a subset of white blood cells (called alpha / beta T cells) from the donor product before the product is transplanted. This study is being done to assess whether this manipulation (called selective T cell depletion) will reduce the risk of GVHD and improve transplant outcome.

Eligibility Criteria

Inclusion Criteria

  • Diagnoses and stage at time of transplant admission: * Acute leukemia (acute myeloid leukemia [AML] or acute lymphoblastic leukemia [ALL] or mixed phenotype acute leukemia [MPAL]) in first or subsequent remission * Myelodysplastic syndromes (MDS) with < 10% marrow blasts * Myeloproliferative neoplasm (MPN) with < 10% marrow blasts * Chronic myelomonocytic leukemia (CMML) with less than 10% marrow blast * Chronic myelogenous leukemia (CML) accelerated phase or second or subsequent chronic phase * Non-Hodgkin’s lymphoma in partial remission (PR) or second complete remission (CR2) or beyond * Hodgkin lymphoma in PR or CR2 or beyond.
  • Patient has a related or unrelated donor who is 8 or 9 out of 10 match at human leukocyte antigen (HLA) A, B, C, DRB1 and DQB1, based on allele level typing.
  • Patient Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Karnofsky >= 60%).
  • Patient deemed to be appropriate candidate for myeloablative conditioning transplantation.
  • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

  • Patient with active human immunodeficiency virus (HIV) infection.
  • Chronic active hepatitis B infection (hepatitis B [HepB] surface antigen [Ag]+ or detectable Hep B viral load).
  • Prior allogeneic hematopoietic stem cell transplantation.
  • Impaired cardiac function- ejection fraction < 40%.
  • Impaired pulmonary function- pretransplant forced expiratory volume in one second (FEV1), diffusion capacity of the lung for carbon monoxide (DLCO) < 50%.
  • Impaired renal function, based on serum creatinine > 2.0 mg/dl.
  • Impaired liver function unrelated to primary disease, based on * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3x upper limit of normal (ULN), or * Total bilirubin > 2.0 mg/dl (with exception for known or suspected Gilbert’s disease).
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Women who are pregnant or breast feeding. Women of child bearing potential must have a negative serum pregnancy test at study entry.
  • Participants who are receiving any other investigational agents are eligible but such agent must be discontinued before admission for hematopoietic stem cell transplantation (HSCT), and if resumption of investigation agent is planned after HSCT, this must be approved by the study principal investigator (PI).
  • Participants with known active central nervous system (CNS) disease. CNS disease that has been treated is eligible.

Locations & Contacts

Massachusetts

Boston
Dana-Farber Cancer Institute
Status: Active
Contact: Vincent Trien-Vinh Ho
Email: vtho@partners.org

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To assess the day 100 severe acute graft versus host disease (GVHD)-free survival rate.

SECONDARY OBJECTIVES:

I. Grades II-IV and III-IV acute GVHD.

II. Chronic GVHD and moderate/severe chronic GVHD.

III. Chronic GVHD-free survival.

IV. Immune suppression-free survival.

V. Hematologic recovery (neutrophil and platelet engraftment).

VI. Immune reconstitution.

VII. Disease relapse.

VIII. Transplant-related mortality.

IX. Organ toxicity (e.g. sinusoidal obstruction syndrome [SOS]/veno-occlusive disease [VOD] and idiopathic pneumonia syndrome [IPS]).

X. Rates of infections (cytomegalovirus [CMV] and Epstein-Barr virus [EBV] reactivation).

XI. Disease-free and overall survival.

XII. Graft-versus-host disease and relapse free survival (GRFS).

OUTLINE:

PREPARATIVE REGIMEN: Patients are assigned to 1 of 2 regimens at the choice of treating physician.

REGIMEN I: Patients receive busulfan intravenously (IV) over 2 hours every 6 hours on days -9 to -7, melphalan IV over 30 minutes on days -6 to -5, and fludarabine IV over 30 minutes on days -6 to -2.

REGIMEN II: Patients undergo fractionated total body irradiation (TBI) thrice daily (TID) on days -10 to -7 for 11 doses. Patients also receive thiotepa IV over 4 hours on days -6 and -5, and fludarabine IV over 30 minutes on days -6 to -2.

TRANSPLANTATION: Patients receive allogeneic TCR alpha/beta-positive T-lymphocyte-depleted peripheral blood stem cells IV over 30-60 minutes on day 0.

After completion of study treatment, patients are followed up at day 100 and at 1 and 2 years.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Dana-Farber Harvard Cancer Center

Principal Investigator
Vincent Trien-Vinh Ho

Trial IDs

Primary ID 18-270
Secondary IDs NCI-2019-01761
Clinicaltrials.gov ID NCT03717480