Blinatumomab and T Cell Depleted Donor Blood Cell Transplant in Treating Younger Patients with Relapsed or Refractory Hematologic Malignancy after a Previous Transplant

Status: Active

Description

This phase II trial studies how well blinatumomab and T cell depleted donor blood cell transplant work in treating children and young adults with hematologic cancer that has not responded or has come back after a previous transplant. White blood cells from donors may be able to kill cancer cells in patients with hematologic cancer. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft-versus-host disease). Removing the T cells from the donor cells before the transplant may stop this from happening. Monoclonal antibodies, such as blinatumomab, may interfere with the ability of cancer cells to grow and spread. Giving blinatumomab after a blood cell transplant may destroy any remaining cancer cells.

Eligibility Criteria

Inclusion Criteria

  • Any of the following hematologic malignancies that has relapsed or remains refractory after prior allogeneic hematopoietic cell transplantation (HCT) (this includes any stage of disease - such as refractory due to induction failure, refractory in relapse, or in any complete remission (CR) - as long as the hematologic malignancy remained persistent or returned after a previous allogeneic HCT): acute lymphoblastic leukemia (ALL), acute myeloblastic leukemia (AML), myeloid sarcoma, chronic myelogenous leukemia (CML), juvenile myelomonocytic leukemia (JMML), myelodysplastic syndrome (MDS), non-Hodgkin lymphoma (NHL)
  • Has a suitable single haplotype matched (>= 3 of 6) family member donor
  • Does not have any other active malignancy other than the one for which this transplant is indicated
  • If prior central nervous system (CNS) leukemia, it must be treated and in CNS CR
  • Does not have current uncontrolled bacterial, fungal, or viral infection
  • Left ventricular ejection fraction > 40%, or shortening fraction >= 25%
  • Creatinine clearance (CrCl) or glomerular filtration rate (GFR) >= 50 ml/min/1.73 m^2
  • Forced vital capacity (FVC) >= 40% of predicted value; or pulse oximetry >= 92% on room air if patient is unable to perform pulmonary function testing
  • Karnofsky or Lansky (age-dependent) performance score >= 50
  • Bilirubin =< 3 times the upper limit of normal for age
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =< 5 times the upper limit of normal for age
  • Not pregnant; if female with child bearing potential, must be confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment
  • Not breast feeding
  • DONOR: At least single haplotype matched (>= 3 of 6) family member
  • DONOR: At least 18 years of age
  • DONOR: Human immunodeficiency virus (HIV) negative
  • DONOR: Not pregnant as confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment (if female)
  • DONOR: Not breast feeding
  • DONOR: Regarding donation eligibility, is identified as either: * Completed the process of donor eligibility determination as outlined in 21 Code of Federal Regulations (CFR) 1271 and agency guidance; OR * Does not meet 21 CFR 1271 eligibility requirements, but has a declaration of urgent medical need completed by the principal investigator or physician sub-investigator per 21 CFR 1271

Locations & Contacts

Tennessee

Memphis
St. Jude Children's Research Hospital
Status: Active
Contact: Brandon Matthew Triplett
Phone: 901-595-3300
Email: referralinfo@stjude.org

Trial Objectives and Outline

PRIMARY OBJECTIVES

I. To estimate engraftment by day +30 post-transplant in patients who receive T cell receptor alpha beta (TCRalphabeta) depleted and cluster of differentiation (CD)45RA-depleted haploidentical donor progenitor cell transplantation following reduced intensity conditioning regimen without radiation.

SECONDARY OBJECTIVES:

I. Assess the safety and feasibility of the addition of blinatumomab in the early post-engraftment period in patients with CD19+ malignancy.

II. Estimate the incidence of malignant relapse, event-free survival, and overall survival at one-year post-transplantation.

III. Estimate incidence and severity of acute and chronic graft versus host disease (GVHD).

IV. Estimate the rate of transplant related mortality (TRM) in the first 100 days after transplantation.

EXPLORATORY OBJECTIVES:

I. Record immune reconstitution parameters, including chimerism analysis, quantitative lymphocyte subsets, T cell receptor excision circle (TREC) analysis, V-beta spectratyping, and lymphocyte phenotype and function.

II. Describe the use of CD45RA-depleted donor lymphocyte infusion (DLI) for recipients who have severe viral infections, disease recurrence or progression, or poor immune reconstitution. Assess and record efficacy of CD45RA-depleted DLI for these conditions, and all adverse events that are related to CD45RA-depleted DLI.

OUTLINE:

Patients receive rabbit anti-thymocyte globulin (ATG) intravenously (IV) daily on days -14, -13, and -12, cyclophosphamide IV once daily (QD) on day -9, fludarabine phosphate IV QD on days -8, -7, -6, -5, and -4, thiotepa IV twice daily (BID) on day -3. Patients receive melphalan IV QD on days -2 and -1, and rituximab IV on day -1. Patients receive sirolimus orally (PO) QD on day 0 until tapering beginning on day 42. Patients undergo TCR alpha beta depleted and CD45RA-depleted haploidentical donor progenitor cell transplantation on days 0 and 1. Patients receive glycosylated recombinant human G-CSF AVI-014 subcutaneously (SC) or IV on days 6 and 7. Beginning 2 weeks post transplantation, patients receive blinatumomab IV continuously for up to 28 days in the absence of disease progression or unexpected toxicity.

After completion of study treatment, patients are followed up at 21 and 100 days, and then annually for up to 10 years.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
St. Jude Children's Research Hospital

Principal Investigator
Brandon Matthew Triplett

Trial IDs

Primary ID REF2HCT
Secondary IDs NCI-2016-00812
Clinicaltrials.gov ID NCT02790515