Addition of Cord Blood Tissue-Derived Mesenchymal Stromal Cells to Ruxolitinib for the Treatment of Steroid-Refractory Acute Graft Versus Host Disease

Sponsor
M.D. Anderson Cancer Center (Other)
Overall Status
Recruiting
CT.gov ID
NCT04744116
Collaborator
National Cancer Institute (NCI) (NIH)
24
1
3
21.4
1.1

Study Details

Study Description

Brief Summary

This early phase I trial is to find out the effect of adding cord blood tissue-derived mesenchymal stromal cells (cb-MSCs) to ruxolitinib in treating patients with acute graft versus host disease that does not respond to steroid therapy (steroid-refractory). Ruxolitinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. cb-MSCs are a type of tissue helper cell that can be removed from donated umbilical cord blood tissue and grown into many different cell types that can be used to treat cancer and other disease, such as graft versus host disease. This trial aims to learn if adding cb-MSCs to ruxolitinib may help control steroid-refractory acute graft versus host disease.

Condition or Disease Intervention/Treatment Phase
Early Phase 1

Detailed Description

PRIMARY OBJECTIVE:
  1. To estimate between-arm differences (Arm 3 versus [vs] Arm 1, and Arm 2 vs Arm 1) for each of the 28-day co-primary outcome probabilities.

OUTLINE: Patients are randomized to 1 of 3 arms.

ARM 1: Patients receive ruxolitinib orally (PO) twice daily (BID) for at least 3 days and may consider tapering after 6 months of therapy if response occurs and therapeutic corticosteroid doses have been discontinued.

ARM 2: Patients receive ruxolitinib PO BID as in Arm 1. Patients also receive lower dose of cb-MSCs intravenously (IV) for up to 60 minutes twice weekly (at least 3 days apart) over 4 consecutive weeks for 8 total doses.

ARM 3: Patients receive ruxolitinib PO BID as in Arm 1. Patients also receive higher dose of cb-MSCs IV for up to 60 minutes twice weekly (at least 3 days apart) over 4 consecutive weeks for 8 total doses.

After completion of study treatment, patients are followed up on day 28 and then for up to 6 months.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
24 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized Controlled Pilot Study of Two Doses of Cord Blood Tissue-Derived Mesenchymal Stromal Cells Combined With Ruxolitinib Versus Ruxolitinib Alone for Therapy of Steroid-Refractory Acute Graft Versus Host Disease
Actual Study Start Date :
Feb 17, 2021
Anticipated Primary Completion Date :
Nov 30, 2022
Anticipated Study Completion Date :
Nov 30, 2022

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Arm 1 (ruxolitinib)

Patients receive ruxolitinib PO BID for at least 3 days and may consider tapering after 6 months of therapy if response occurs and therapeutic corticosteroid doses have been discontinued.

Drug: Ruxolitinib
Given PO
Other Names:
  • INCB-18424
  • INCB18424
  • Jakafi
  • Oral JAK Inhibitor INCB18424
  • Experimental: Arm 2 (ruxolitinib, lower dose ds-MSCs)

    Patients receive ruxolitinib PO BID as in Arm 1. Patients also receive lower dose of cb-MSCs IV for up to 60 minutes twice weekly (at least 3 days apart) over 4 consecutive weeks for 8 total doses.

    Other: Cellular Therapy
    Given ds-MSCs IV
    Other Names:
  • Cell Therapy
  • Drug: Ruxolitinib
    Given PO
    Other Names:
  • INCB-18424
  • INCB18424
  • Jakafi
  • Oral JAK Inhibitor INCB18424
  • Experimental: Arm 3 (ruxolitinib, higher dose ds-MSCs)

    Patients receive ruxolitinib PO BID as in Arm 1. Patients also receive higher dose of cb-MSCs IV for up to 60 minutes twice weekly (at least 3 days apart) over 4 consecutive weeks for 8 total doses.

    Other: Cellular Therapy
    Given ds-MSCs IV
    Other Names:
  • Cell Therapy
  • Drug: Ruxolitinib
    Given PO
    Other Names:
  • INCB-18424
  • INCB18424
  • Jakafi
  • Oral JAK Inhibitor INCB18424
  • Outcome Measures

    Primary Outcome Measures

    1. Death from any cause [Within 28 days from the start of active study treatment]

    2. Response [At day 28 from start of therapy on study]

      Will compare the patient's 28-day graft versus host disease (GVHD) status to the patient's baseline GVHD status when steroid refractory acute GVHD was diagnosed.

    3. Incidence of adverse events [Within 28 days from the start of active study treatment]

    Secondary Outcome Measures

    1. Graft versus host disease status [At days 7, 14, 21 and 28 post treatment]

      Will assess complete response (CR), very good partial response (VGPR), partial response (PR), stable disease (SD), and progressive disease (PD).

    2. Proportion of response [At days 7, 14, 21 and 28 post treatment]

      Will assess proportion of patients with CR, PR, VGPR, and no-response (NR). The event NR is defined as stable disease, mixed response, disease progression, OR initiation of additional systemic (second-line) GVHD therapies.

    3. Time to complete response [Up to 6 months]

      Will be estimated by the method of Kaplan and Meier.

    4. Time to very good partial response [Up to 6 months]

      Will be estimated by the method of Kaplan and Meier.

    5. Time to partial response [Up to 6 months]

      Will be estimated by the method of Kaplan and Meier.

    6. Incidence of complete response for each organ [Up to 6 months]

    7. Incidence of very good partial response for each organ [Up to 6 months]

    8. Incidence of partial response for each organ [Up to 6 months]

    9. Durability of organ response [Up to 6 months]

    10. Cumulative incidence of non-relapse mortality (NRM) [At 6 months post treatment]

    11. Cumulative incidence of relapse/progression of the primary disease [At 6 months]

    12. Overall survival [From enrollment to death from any cause, assessed at 6 months]

    13. Disease-free survival [From enrollment to death from any cause or relapse/progression of the primary disease, assessed at 6 months]

    14. Graft versus host disease-free survival [At 6 months]

      Patients alive, free of active acute or chronic GVHD, and without other systemic agents (or escalation of steroids to >= 2.5 mg/kg/day of prednisone [or methylprednisolone equivalent of 2 mg/kg/day]) added for treatment of GVHD will be considered successes for this endpoint

    15. Incidence of chronic graft versus host disease [At 6 months after first mesenchymal stromal cells (MSC) infusion]

      Chronic GVHD is defined per National Institutes of Health Consensus Criteria. Diagnosis of chronic GVHD of any severity (mild, moderate, or severe) is considered an event for this endpoint. Organ involvement and maximum severity will also be described at six months.

    16. Incidence of systemic infections [28 days after last study drug]

      The incidence of grade 2 to 3 systemic infections occurring from study treatment until 28 days after last study drug will be described using standard Common Terminology Criteria for Adverse Events (CTCAE) criteria. Infections will be recorded by site of disease, date of onset, and severity.

    17. Incidence of toxicities [Up to 28 days after completing last MSC infusion study drug]

      The incidence of grade 3-5 treatment-emergent adverse events (per CTCAE version 5.0) that occur through 28 days after completing last MSC infusion study drug will be described.

    18. Incidence of any grade cytokine release [Up to 28 days after completing last MSC infusion study drug]

    19. Incidence of any infusional toxicity [Within 24 hours of each cord blood-MSC infusion]

    Other Outcome Measures

    1. Cytokine biomarker analysis (optional) [Up to 6 months]

      Will use cytokine biomarker assays to predict response to therapy.

    2. Fecal samples analysis (optional) [Up to 6 months]

      Will use fecal samples to assess microbiome and potential predictor for response to therapy.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    12 Years to 80 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Patients between the ages of 12 years and 80 years (inclusive).

    2. Steroid refractory grades II-IV acute GVHD of the Lower GI tract or Liver (including those developing these manifestations after previous acute GVHD of skin) secondary to allogeneic HCT or donor lymphocyte infusion. (Grading, see Appendix I) GVHD with: No improvement after treatment with methylprednisolone at ≥ 2.0 mg/kg/day or equivalent for minimum 7 days, or progressive symptoms after minimum 3 days, or a flare in acute GVHD while on systemic steroids. Patients must have had a biopsy that suggests GVHD; a repeat biopsy to enroll on the study is not necessary.

    3. Estimated creatinine clearance ≥ 30 mL/min

    4. Karnofsky/Lansky Performance score of at least 30 at the time of study entry.

    5. Patients who are women of childbearing potential, must be non-pregnant, not breast-feeding, and use adequate contraception. Male patients must use adequate contraception

    6. Patient (or legal representative where appropriate) must be capable of providing written informed consent, and assent if indicated.

    Exclusion Criteria:
    1. De novo chronic GVHD

    2. Isolated acute GVHD of skin

    3. Secondary systemic therapy for acute GVHD ruxolitinib greater than 96 hours before initiation of therapy.

    4. Primary treatment with agents other than alpha-1 antitrypsin (AAT) glucocorticoids and ruxolitinib.

    5. Patients with uncontrolled infections will be excluded. Infections are considered controlled if appropriate therapy has been instituted and, at the time of enrollment, no signs of progression are present. Progression of infection is defined as hemodynamic instability attributable to sepsis, new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.

    6. Patient with significant supplemental oxygen requirement defined as >6 L oxygen by nasal cannula.

    7. Patient with known allergy to bovine or porcine products.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 M D Anderson Cancer Center Houston Texas United States 77030

    Sponsors and Collaborators

    • M.D. Anderson Cancer Center
    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Partow Kebriaei, MD, M.D. Anderson Cancer Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    M.D. Anderson Cancer Center
    ClinicalTrials.gov Identifier:
    NCT04744116
    Other Study ID Numbers:
    • 2019-1122
    • NCI-2020-13889
    • 2019-1122
    • P01CA148600
    First Posted:
    Feb 8, 2021
    Last Update Posted:
    Jul 12, 2022
    Last Verified:
    Jul 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jul 12, 2022