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Multi-Ctr PII Cmb.Modality Tx Ruxolitinib, Decitabine, and DLI for Post HSCT in AML/MDS

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ClinicalTrials.gov Identifier: NCT04055844
Recruitment Status : Recruiting
First Posted : August 14, 2019
Last Update Posted : January 22, 2021
Sponsor:
Collaborator:
Incyte Corporation
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Brief Summary:
This is a multi-center, single-arm, open-label, phase II trial for the frontline treatment of relapsed AML or MDS following allo-HCT. Eligible subjects will receive up to 4 cycles of combined modality treatment. The number of cycles depends on response, toxicity, and the remaining cell dose.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Myeloid and Monocytic Leukemia Myelodysplastic Syndromes Drug: Decitabine Drug: Ruxolitinib Drug: Donor Lymphocyte Infusion (DLI) Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 34 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multi-Center Phase 2 Study of Combined Modality Treatment With Ruxolitinib, Decitabine, and Donor Lymphocyte Infusion for Post-Transplant Relapse of AML or MDS
Actual Study Start Date : February 17, 2020
Estimated Primary Completion Date : January 2025
Estimated Study Completion Date : January 2025


Arm Intervention/treatment
Experimental: Decitabine + Ruxolitinib + DLI
Eligible subjects will receive up to 4 cycles of combined modality treatment. The number of cycles depends on response, toxicity, and the remaining cell dose.
Drug: Decitabine
10 days of decitabine 20 mg/m2 IV daily; or, alternatively, per institution, physician, or patient preference on a 5-2-5 schedule with no weekend infusion. If a CR is achieved after 2 cycles using the 10-day schedule, subsequent cycles will change to a 5-day schedule.

Drug: Ruxolitinib
Starting with day 1 of cycle 1 and continuing for up to 6 months after the end of the last cycle, patients will receive ruxolitinib 5 mg twice daily orally. Dose may be increased to 10 mg twice daily in cycles 2 through 4 if platelets improve to >100 x 10^9/L.

Drug: Donor Lymphocyte Infusion (DLI)
DLI from the original donor will be infused within 10 days after the last dose of decitabine in each cycle.




Primary Outcome Measures :
  1. Efficacy of combined modality treatment (ruxolitinib, decitabine, and DLI) for relapsed AML or MDS post allo-HCT: Rate of Overall Survival (OS) [ Time Frame: 6 Months ]
    Rate of Overall Survival (OS)


Secondary Outcome Measures :
  1. Efficacy of combined modality treatment (ruxolitinib, decitabine, and DLI) for relapsed AML or MDS post allo-HCT: Rate of Overall Survival (OS) [ Time Frame: 1 Year ]
    Rate of Overall Survival (OS)

  2. Grade II-IV acute graft-versus-host disease (aGVHD II-IV) [ Time Frame: 3 Months ]
    Cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD II-IV)

  3. Progression Free Survival (PFS) [ Time Frame: 6 Months ]
    Rate of Progression Free Survival (PFS)

  4. Progression Free Survival (PFS) [ Time Frame: 1 Year ]
    Rate of Progression Free Survival (PFS)

  5. Relapse [ Time Frame: 6 Months ]
    Cumulative Incidence of Relapse

  6. Relapse [ Time Frame: 1 Year ]
    Cumulative Incidence of Relapse

  7. Complete Remission (CR) [ Time Frame: 6 Months ]
    Rate of Complete Remission (CR)

  8. Complete Remission (CR) [ Time Frame: 1 Year ]
    Rate of Complete Remission (CR)

  9. Non-Relapse Mortality (NRM) [ Time Frame: 6 Months ]
    Cumulative Incidence of Non-Relapse Mortality (NRM)

  10. Non-Relapse Mortality (NRM) [ Time Frame: 1 Year ]
    Cumulative Incidence of Non-Relapse Mortality (NRM)

  11. Best Response [ Time Frame: 1 Year ]
    Best response until next line of treatment, death, or last follow up, whichever occurs sooner



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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Patient Inclusion Criteria:

  • Age ≥12 years
  • Have undergone first allo-HCT from a 6/6 matched sibling donor, 8/8 matched unrelated donor, or an HLA haploidentical donor.
  • History of AML or MDS for which allo-HCT was performed. Overlap MPN/MDS is included.
  • Untreated relapse of the underlying malignancy as defined by >5% of malignant blasts (by morphology and/or flow cytometry) in the bone marrow, or myeloid sarcoma.
  • Additional cells sufficient for the first DLI available from the same donor, or the donor must be willing to donate. Both G-CSF mobilized and unmobilized products are allowed and the choice is at the discretion of the treating physician.
  • Partial (or better) engraftment from the bone marrow showing relapse, defined as >50% donor chimerism on non-split RFLP. Patients with chimerism of 25-50% may be enrolled with approval of the site PI and Sponsor/Investigator
  • Karnofsky performance status ≥ 50%
  • Adequate organ function within 14 days of study registration defined as:

    • Total bilirubin < 1.5 x upper limit of institutional normal, unless a diagnosis of Gilbert's disease
    • AST/ALT < 2.5 x upper limit of institutional normal
    • Creatinine clearance ≥40 mL/minute as calculated by the Cockcroft-Gault formula. Cockcroft-Gault CrCl = (140-age) * (Wt in kg) * (0.85 if female) / (72 * Cr).
  • Peripheral white blood cell count <50 x 10^9/L. The use of hydroxyurea for cytoreduction is allowed and may continue until cycle 2 day 1
  • Subjects and spouse/partner who are of childbearing potential must be using highly effective contraception consisting of 2 forms of birth control (at least 1 of which must be a barrier method) starting at Screening and continuing through the entire study (for at least 3 months after the last dose of ruxolitinib if study treatment is stopped early or subject withdraws consent). Highly effective contraception is defined as:

    • Established use of oral, injected or implanted hormonal methods of contraception.
    • Placement of an intrauterine device or intrauterine system.
    • Double barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository (double barrier method will count as 2 forms of contraception).
  • Male subjects must not donate sperm during the Screening and Treatment Periods, and for at least 3 months after the last dose of ruxolitinib.
  • Subjects are willing and able to give written informed consent and to comply with all study visits and procedures. Parents or legal guardians will consent for minors and minors will be asked to assent.

Patient Exclusion Criteria:

  • Active uncontrolled infection at the time of consent. An active uncontrolled infection is defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without signs or symptoms of infection will not be interpreted as an active uncontrolled infection. Subjects with a controlled infection receiving definitive therapy for 72 hours prior to enrollment are eligible.
  • History of infection with human immunodeficiency virus (HIV), unresolved hepatitis B, or hepatitis C.
  • Untreated CNS leukemia
  • Untreated or active GVHD (acute or chronic)
  • History of grade III-IV acute GVHD at any point in time
  • Any form of iatrogenic immunosuppression except <0.5 mg/kg/day of prednisone or equivalent at the time of consent.
  • Unresolved veno-occlusive disease of the liver, defined as persistent bilirubin abnormalities not attributable to GVHD and ongoing organ dysfunction (renal, ascites).
  • Subjects who are pregnant, breast feeding or sexually active and unwilling to use effective birth control for the duration of the study, as agents in this study are in pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, and category D: there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans.
  • Radiation therapy within 14 days prior to consent.
  • Any prior therapy for relapse after allo-HCT.
  • Prior DLI. CD34-selected boost is allowed
  • Exposure to any other investigational agent, device or procedure within 14 days prior to consent
  • Patients or donors with any medical or psychological condition that, in the opinion of the Investigator, might interfere with the subject's participation in the trial, pose any additional risk for the patient/donor, or confounds the assessments of the subject.
  • Subjects with known allergies, hypersensitivity or intolerance to ruxolitinib or similar compounds.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04055844


Contacts
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Contact: Carol Rose, RN 612-273-2800 crose1@fairview.org
Contact: Tammy Grainger 612-273-2800 tgraing1@fairview.org

Locations
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United States, Minnesota
Masonic Cancer Center, University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Armin Rashidi, MD         
United States, Missouri
Washington University Medical School Recruiting
Saint Louis, Missouri, United States, 63130
Contact: Mark Schroeder, MD         
United States, New York
University of Rochester Medical Center Recruiting
Rochester, New York, United States, 14642
Contact: Eric Huselton, MD         
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Incyte Corporation
Investigators
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Principal Investigator: Armin Rashidi, MD, PhD Division of Hematology, Oncology and Transplantation, University of Minnesota
Principal Investigator: Mark A Schroeder, M.D. Washington University School of Medicine
Principal Investigator: John F Dipersio, M.D., Ph.D. Washington University School of Medicine
Principal Investigator: Eric Huselton, M.D. University of Rochester
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Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT04055844    
Other Study ID Numbers: 2018LS066
MT2018-07 ( Other Identifier: University of Minnesota Masonic Cancer Center )
First Posted: August 14, 2019    Key Record Dates
Last Update Posted: January 22, 2021
Last Verified: January 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Masonic Cancer Center, University of Minnesota:
AML
MDS
Additional relevant MeSH terms:
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Leukemia
Myelodysplastic Syndromes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Decitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors