Summary

for people ages 18 years and up (full criteria)
at La Jolla, California
study started
estimated completion:
Dimitrios Tzachanis Divya Koura

Description

Summary

The purpose of this study is to investigate whether the combination of cyclophosphamide and abatacept versus the treatment used in standard of care will reduce the incidence of moderate and severe chronic graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation. GVHD occurs when the cells from your donor (the graft) see your body's cells (the host) as different and attack them.

Official Title

A Randomized Phase II Trial Comparing a Calcineurin Inhibitor-free Graft-versus-host Disease Prophylaxis Regimen With Post-transplantation Cyclophosphamide and Abatacept to Standard of Care

Details

The experimental GVHD prophylaxis arm consists of cyclophosphamide and abatacept. Cyclophosphamide induces apoptosis of activated T cells and abatacept (CTLA4Ig) blocks activation of T cells by inhibiting the co-stimulatory signal.

Compared to the standard-of-care control arm, the experimental arm is much more convenient and expected to be associated with fewer toxicities.

In addition there is a great theoretical potential for immunological synergy between cyclophosphamide and abatacept for inducing post-transplant immunologic tolerance that clinically might translate into less GVHD without increase in relapse Patients will be randomized 1:1 to the experimental vs the standard of care arm. Randomization will be done prior to the use of any conditional therapy.

The two arms will be stratified by disease (acute leukemia vs others) and donor type (MRD vs MUD/MUD vs Haplo) in an effort to keep them balanced.

The conditioning regimen for both arms will be mainly Busulfan/Fludarabine (A Total Body Irradiation based conditioning regimen will be allowed for diseases such as ALL)

The GVHD prophylaxis regimen on the experimental arm will consist of high dose Cyclophosphamide on Days +3 and +4 followed by abatacept for 6 months.

The GVHD prophylaxis regimen on the standard of care arm will consist of methotrexate on Days +1,+3, +6 and +11 and tacrolimus for patients with a 10/10 matched related or unrelated donor and of high dose cyclophosphamide on Days +3 and +4 followed by tacrolimus and mycophenolate for patients with a haploidentical donor.

Keywords

GVHD Hematologic Neoplasms cancer Graft-Versus-Host Disease Abatacept Cyclophosphamide GVHD prophylaxis stem cell transplantation High risk hematologic malignancy hematologic malignancy Allogeneic Hematopoetic Stem Cell Transplantation Graft vs Host Disease Methotrexate Tacrolimus Calcineurin Inhibitors Cyclophosphamide and abatacept methotrexate and tacrolimus

Eligibility

You can join if…

Open to people ages 18 years and up

  • High risk hematologic malignancy justifying the need for an allogeneic hematopoetic stem cell transplantation: AML, ALL, CML in accelerated or blast phase, MDS/MPN, NHL,Hodgkin lymphoma, and multiple myeloma
  • Creatinine clearance > 40
  • Adequate hepatic function
  • Normal cardiac function (EF > 50%)

You CAN'T join if...

  • Patients with hematologic malignancies for which transplant is not the only curative option, such as AML with good or intermediate cytogenetics or molecular markers in CR1 or CML in chronic phase
  • Inability to identify an 10/10 HLA-Matched Donor (related or unrelated) or a haploidentical donor
  • Active malignant disease relapse
  • Active, uncontrolled infection, uncontrolled cardiac angina, symptomatic congestive heart failure
  • Life expectancy <3 months
  • Pregnancy or lactation
  • Patients may not be receiving any other investigational agents in the last 28 days
  • Patients with chronic myeloid leukemia in first chronic phase

Location

  • UC San Diego Moores Cancer Center
    La Jolla California 92093 United States

Lead Scientists

  • Dimitrios Tzachanis
    Assistant Clinical Professor, Medicine. Authored (or co-authored) 30 research publications
  • Divya Koura
    Assistant Clinical Professor, Medicine. Authored (or co-authored) 5 research publications

Details

Status
not yet accepting patients
Start Date
Completion Date
(estimated)
Sponsor
Dimitrios Tzachanis, MD PhD
ID
NCT03680092
Phase
Phase 2
Study Type
Interventional
Last Updated