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

A Phase I Study To Evaluate the Safety of Umbilical Cord - Derived, Ex-Vivo Cultured and Expanded Wharton's Jelly Mesenchymal Stem Cells for the Treatment of De Novo High Risk Acute or Steroid Refractory Acute Graft Versus Host Disease

This study evaluates the safety and effectiveness of two different doses of umbilical cord derived, ex-vivo cultured and expanded Wharton's jelly mesenchymal stem cells (MSCTC-0010) in the treatment of acute Graft versus Host Disease (aGVHD). The first 5 participants enrolled in the study will receive a lower dose of MSCTC-0010. If none of the first 5 participants have treatment-related serious adverse events (TRSAEs) for 42 days, then the next 5 participants will receive a slightly higher dose of MSCTC-0010.

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.