A Randomized, Prospective, Double Blind, Placebo-Controlled, Phase 3 Study of US-ATG-F Prophylaxis as a Supplement to Standard of Care Prophylaxis to Prevent Moderate to Severe Chronic GVHD in Adult Acute Myeloid Leukemia, Acute Lymphoid Leukemia, and Myelodysplastic Syndrome Patients After Allogeneic Stem Cell Transplantation From Unrelated Donors

Study ID
STU 062011-119

Cancer Related
Yes

Healthy Volunteers
No

Study Sites

Contact
James Pond
214-648-7030
blake.pond@utsouthwestern.edu

Principal Investigator
Madhuri Vusirikala

Summary

This is a randomized (1:1), prospective, double blind, placebo-controlled, multicenter, phase 3 study comparing uS-aTG-F prophylaxis as a supplement to standard of care prophylaxis for moderate to severe chronic GVHD-free survival in adult acute myeloid leukemia (aML), acute lymphoid leukemia (aLL), and myelodysplastic syndrome (MDS) patients after allogeneic stem cell transplantation from unrelated donors.

The investigator will determine which of four conditioning regimens is optimal for the patient prior to randomization (see Section 3.4.3.1). Patients meeting all the inclusion criteria and none of the exclusion criteria will be randomized (1:1), immediately prior to start of conditioning regimen, (typically Days -7 or -6), to either a uS-aTG-F or placebo treatment. all patients will receive pre-medication and study drug (uS-aTGF or normal saline) on the three days (Study Day -3, Study Day -2, and Study Day -1) prior to transplantation on Study Day 0. all patients will also receive the current standard prophylactic regimen for GVHD which consists of tacrolimus (TaC) plus methotrexate (MTX).

Transplantation will take place on Study Day 0. an intensive post-transplant followup period of a month (from Study Day 0 to Study Day +30 (+-) 3 days) will follow and includes standard GVHD prophylaxis treatment, daily physical examinations, special examinations (i.e. chest X-ray, abdominal ultrasounds) and laboratory evaluations. a long-term follow-up period will ensue from post-transplant day +30 to day +360 or end of study whichever occurs later.

optional blood collection for marker substudy for patients of uS sites may be performed at Study Days +30, +100, +180, and +360 (appendix J of the protocol).

The primary endpoint is moderate to severe chronic GVHD-free survival after allogeneic stem cell transplantation defined as the time from first study drug administration until the first occurrence of moderate to severe chronic GVHD according to niH criteria or death from any cause.a Cox regression model will be utilized including the factors source of stem cells (bone marrow/peripheral blood), status of disease (early/intermediate) and age ([LessThanorequalTo]40 /[Greater Than]40 years)

The secondary efficacy endpoints of this study are to compare the treatment arms of
uS-aTG-F plus standard GVHD prophylaxis versus Placebo plus standard GVHD
prophylaxis with respect to:
* incidence of and time to acute GVHD (grades i-iV, ii-iV, iii-iV)
* incidence of and time to mild to severe, moderate to severe, and severe chronic
GVHD (niH score 1-3, niH score 2-3, niH score 3)
* overall survival and transplant related mortality
* incidence of and time to relapse
* incidence of and time to start of systemic immunosuppressive medication for
treatment of chronic GVHD
* Secondary safety endpoints are adverse events with emphasis on adverse drug
reactions, infections, de novo malignancies, time to neutrophil recovery, time to
platelets recovery, and incidence of primary graft failure.

Participant Eligibility

1. Men or women between 18 to 65 years of age, inclusive
2. Patients designated to undergo allogeneic peripheral blood or bone marrow stem
cell transplantation following the diagnosis of one of the following primary
diseases in early or intermediate disease status:

* AML at the following stages: 1st remission, 2nd remission, and 3rd or
subsequent remission1

* ALL at the following stages: 1st remission, 2nd remission, and 3rd or
subsequent remission1

* MDS (FAB classification types RA, RARS or RAEB-1)
3. Patients with an unrelated HLA-A, -B, -C, and -DRB1, matched (all by high
resolution typing) donor (8 out of 8 alleles)
4. Patients with a Karnofsky Performance Score (KPS) >= 70%
5. Patients who performed all the required screening examinations
6. Female patients must be surgically sterile, postmenopausal (minimum 1 year
without menses), or agree to use one or more of the following forms of
contraception from the time of signing the informed consent form through
Day +180: hormonal (i.e., oral, transdermal, implant, or injection); double barrier
(i.e., condom, diaphragm with spermicide); intrauterine device (IUD);
vasectomized partner (six months minimum); or abstinence. Male patients must
also agree to use one or more of the above forms of birth control for either
themselves or their partner, as appropriate, from the time of signing the informed
consent form through Day +180
7. Patients capable of understanding the purposes and risks of the study, who are
willing and able to participate in the study and from whom written and dated IRBapproved
informed consent has been obtained