Evaluation of Umbilical Cord-Derived Wharton's Jelly Stem Cells for the Treatment of Acute Graft Versus Host Disease

The curative potential of Allogeneic hematopoietic stem cell transplantation (allo-HCT), when
applied as a therapy in the management of hematologic malignancies, specifically, derives
from an immunologically driven, graft-versus-tumor effect mediated principally by donor
T-cells, and is associated with a lesser risk for relapse when compared to high dose
chemo-radio therapy and autologous HCT. Donor derived T-cells are also responsible for
mediating the occurrence of GVHD, a common transplant-related complication, affecting a
significant percentage of patients undergoing allo-HCT leading to the destruction of host
tissues. The standard initial treatment for both acute and chronic GVHD is steroid-based
therapy. Unfortunately, many of these patients will become resistant to steroid therapy and
will subsequently be treated with second-line immunosuppressive agents. De novo high-risk
aGVHD and steroid-refractory aGVHD portends a very poor prognosis; second-line agents
frequently prove ineffective, and as a result, survival is < 10% at 5 years. Therefore,
alternative therapies are needed to treat aGVHD following allo-HCT, particularly in the
setting of de novo high-risk acute or steroid-resistant disease.

Due to the large numbers of Mesenchymal stem cells (MSC) that can be obtained from the
umbilical cord, the availability of this tissue, their higher growth rates and expansion
capacity, and their immune properties, including: (1) low immunogenicity and lack of
stimulation of allogeneic T-lymphocyte proliferation, (2) suppression of the proliferation of
activated T-lymphocytes, (3) increased production of regulatory T-cells, and (4) a shift in
the immune response towards tolerance, Wharton's jelly mesenchymal stem cells (WJMSC) may be
a preferred option for MSC.

The rationale for cell dosing in this protocol is based on published data from Kebriaei, et
al. Dosing at 2 × 10^6 MSC/kg body weight produced a complete response in 87.5% of the
treated patients. Dosing at a level 4 times higher (8 × 10^6 MSC/kg body weight) produced no
improvement in complete response results. However, the higher dose produced some partial
response and no patient failed to respond to therapy. Therefore, the Phase I study for
MSCTC-0010 is designed to increase the dose of WJMSC from 2 × 10^6 MSC to 10 × 10^6 MSC/kg
body weight, assuming no dose-limiting toxicity (DLT) is observed at the lower dose.

Inclusion Criteria:

- Age: ≥ 18 years of age and ≤ 75 years of age.

- Women of child-bearing potential and men with partners of child-bearing potential must
agree to practice sexual abstinence, or to use two forms of adequate contraception
(hormonal AND barrier method of birth control) prior to study entry, for the duration
of study participation, and for 90 days following completion of therapy. If a woman
becomes pregnant or suspects she is pregnant while participating in this study, she
should inform her treating physician immediately.

- A woman of child-bearing potential is any female (regardless of sexual
orientation, having undergone a tubal ligation, or remaining celibate by choice)
who meets the following criteria:

- Has not undergone a hysterectomy or bilateral oophorectomy; OR

- Has not been naturally postmenopausal for at least 12 consecutive months
(i.e., has had menses at any time in the preceding 12 consecutive months)

- Men of child-bearing potential must not donate sperm while on this study and for
90 days after their last study treatment.

- NOTE: Acceptable forms of birth control are listed below:

- One Barrier method (cervical cap with spermicide plus male condom; diaphragm
with spermicide plus male condom) PLUS

- Hormonal method (oral contraceptives, implants, or injections) or an
intrauterine device (e.g., Copper-T).

- Participant must have de novo HR or steroid refractory, Grade II-IV aGVHD as defined
in Appendix 1. NOTE: Biopsy at screening only for evaluation of aGVHD is not
mandatory, but is recommended when feasible. Enrollment should not be delayed awaiting
biopsy results.

- Participant must have received an allogenic transplant at Kansas University Cancer
Center/University of Kansas Medical Center (KUCC / KUMC).

Exclusion Criteria:

- Participants may not have received any other investigational agent used to treat acute
GVHD for 30 days prior to enrollment.

- Participant has any underlying or current medical or psychiatric condition that, in
the opinion of the Investigator, would interfere with the evaluation of the
participant.