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

NCT04055844 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2018LS066MT2018-07
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 3

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.

Conditions

Acute Myeloid Leukemia; Myeloid and Monocytic Leukemia; Myelodysplastic Syndromes

Keywords

AML; MDS

Outcome Measures

Primary Outcomes (1)

• Efficacy of Combined Modality Treatment (Ruxolitinib, Decitabine, and DLI) for Relapsed AML or MDS Post Allo-HCT: Rate of Overall Survival (OS)

  Rate of Overall Survival (OS)

  6 Months

Secondary Outcomes (11)

• Efficacy of Combined Modality Treatment (Ruxolitinib, Decitabine, and DLI) for Relapsed AML or MDS Post Allo-HCT: Rate of Overall Survival (OS)

  1 Year

• Percentage of Participants With Grade II-IV Acute Graft-versus-host Disease (aGVHD II-IV)

  3 Months

• Progression Free Survival (PFS)

  6 Months

• Progression Free Survival (PFS)

  1 Year

• Relapse

  6 Months

Study Arms (1)

Decitabine + Ruxolitinib + DLI

EXPERIMENTAL

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; Drug: Ruxolitinib; Drug: Donor Lymphocyte Infusion (DLI)

Interventions

Decitabine DRUG

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.

Decitabine + Ruxolitinib + DLI

Ruxolitinib DRUG

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.

Decitabine + Ruxolitinib + DLI

Donor Lymphocyte Infusion (DLI) DRUG

DLI from the original donor will be infused within 10 days after the last dose of decitabine in each cycle.

Decitabine + Ruxolitinib + DLI

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead
• Incyte Corporation: collaborator

Study Sites (3)

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Washington University Medical School

St Louis, Missouri, 63130, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Monocytic, Acute; Myelodysplastic Syndromes

Interventions

Decitabine; ruxolitinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Mark Juckett , MD
• Organization: University of Minnesota, Masonic Cancer Center

juck0001@umn.edu

612-676-4200

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2019
• First Posted: August 14, 2019
• Study Start: February 17, 2020
• Primary Completion: September 6, 2022
• Study Completion: September 6, 2022
• Last Updated: November 7, 2023
• Results First Posted: November 7, 2023

Record last verified: 2023-11

Locations

US (3)