Using Inqovi to prevent relapse in myeloid neoplasms after stem cell transplant

A Phase Ib Study of Oral Decitabine/Cedazuridine as Maintenance Therapy Following Allogeneic Hematopoietic Cell Transplantation for Patients With Myeloid Neoplasms

This study is testing if a new treatment called Inqovi can help prevent relapse in people with myelodysplastic syndromes or chronic myelomonocytic leukemia after they have had a stem cell transplant.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 22 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Massachusetts General Hospital (Academic / other)
• Locations: 1 site (Boston, Massachusetts)
• Trial ID: NCT04980404 on ClinicalTrials.gov

What this trial studies

This study investigates the effectiveness of Inqovi, a combination of decitabine and cedazuridine, as maintenance therapy for patients with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML) following allogeneic hematopoietic cell transplantation. It is a phase Ib, non-randomized, open-label trial where participants will receive varying doses of Inqovi based on their tolerance and safety. The study aims to determine the highest safe dose of Inqovi while monitoring participants for up to 24 months post-treatment. Approximately 22 individuals will be enrolled in this research, which is supported by Taiho Oncology, Inc.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with a confirmed diagnosis of MDS or CMML who are undergoing their first allogeneic stem cell transplant.

Not a fit: Patients who do not have a confirmed diagnosis of MDS or CMML or those who are not undergoing stem cell transplantation may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce the risk of relapse in patients with myeloid neoplasms after stem cell transplantation.

How similar studies have performed: While Inqovi has been approved for MDS and CMML, its use in the post-transplant setting is novel and has not been extensively tested in similar studies.

Eligibility criteria

Inclusion Criteria:

* Pathologically confirmed diagnosis of myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML).

  * Subjects should have less than 5% myeloblasts on a bone marrow biopsy within 42 days prior to the start of conditioning.
* Age ≥ 18
* Will undergo first allogeneic hematopoietic stem cell transplantation (HSCT) for their malignancy.
* Transplantation will be performed with the use of reduced intensity conditioning (RIC).
* HSCT Donor will be one of the following:

  * 5/6 or 6/6 (HLA-A, B, DR) matched related donor
  * 7/8 or 8/8 (HLA-A, B, DR, C) matched unrelated donor. Matching in the unrelated setting must be at the allele level.
  * Haploidentical related donor, defined as ≥ 3/6 (HLA-A, B, DR) matched
  * ≥ 4/6 (HLA-A, B, DR) umbilical cord blood (UCB). Matching in the UCB setting is at the antigen level. Recipients may receive either one or two UCB units. In the case of 2 UCB units, both units must have been at least 4/6 matched with the recipient.
* ECOG performance status 0-2.
* Participants must have normal organ and function as defined below:

  * AST (SGOT), ALT (SGPT) and Alkaline phosphatase \< 3x institutional upper limit of normal (ULN)
  * Total bilirubin \< 1.5 x ULN (with the exception of subjects with a history of Gilbert's syndrome)
  * Calculated creatinine clearance ≥ 30 mL/min (Cockcroft-Gault formula)
* LVEF must be equal to or greater than 50%, as measured by MUGA scan or echocardiogram
* Female patients of childbearing potential must have a negative pregnancy test, as measured by serum or urine testing
* The effects of decitabine/cedazuridine on the developing human fetus are unknown. For this reason women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) during the entire study treatment period and through 6 months after the last dose of treatment
* Ability to understand and the willingness to sign a written informed consent document.

Eligibility Criteria Prior to Treatment (Post HCT)

* Maintenance therapy may begin at any time between day 30 and day 120 following hematopoietic cell transplantation. Participants must meet the following criteria to be eligible to treatment on this study:

  * Chimerism studies reveal that ≥ 70% of blood or bone marrow cells, or of the CD33 expressing fraction, are of donor origin.
  * There is no acute graft versus host disease (GVHD), requiring an escalation of corticosteroid dose or addition of other agent in the 4 weeks prior to Cycle 1 Day 1.
  * There is no morphological evidence of relapsed/recurrent/residual disease (as assessed by post HCT bone marrow biopsy and aspirate).
  * There is no systemic infection requiring IV antibiotic or antifungal or antiviral therapy within 7 days of starting decitabine/cedazuridine
  * ANC ≥ 1000/µL
  * Platelets ≥ 50,000/µL
  * AST (SGOT), ALT (SGPT) and Alkaline phosphatase \< 3x institutional upper limit of normal (ULN)
  * Total bilirubin \< 1.5 x ULN (with the exception of subjects with a history of Gilbert's syndrome)
  * Calculated creatinine clearance ≥ 30 mL/min (Cockcroft-Gault formula)

Exclusion Criteria:

* Prior allogeneic hematopoietic stem cell transplants.
* History of other malignancy(ies) unless

  * the participant has been disease-free for at least 12 months and is deemed by the investigator to be at low risk of recurrence of that malignancy, or
  * the only prior malignancy was cervical cancer in situ and/or basal cell or squamous cell carcinoma of the skin
* Known diagnosis of active hepatitis B or hepatitis C
* Current or history of congestive heart failure New York Heart Association (NHYA) class 3 or 4, or any history of documented diastolic or systolic dysfunction (LVEF \< 50%, as measured by MUGA scan or echocardiogram)
* Current or history of ventricular or life-threatening arrhythmias or diagnosis of long-QT syndrome
* Systemic uncontrolled infection
* Known dysphagia, short-gut syndrome, gastroparesis, or other condition(s) that limits the ingestion or gastrointestinal absorption of drugs administered orally
* Uncontrolled hypertension (systolic blood pressure \[BP\] \> 180 mmHg or diastolic BP \> 100 mmHg)
* QTc interval (i.e., Friderica's correction \[QTcF\]) ≥ 450 ms or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) at screening
* Uncontrolled intercurrent illness that would limit compliance with study requirements.
* Breastfeeding women

Where this trial is running

Boston, Massachusetts

• Massachusetts General Hospital — Boston, Massachusetts, United States (Recruiting)

Study contacts

• Principal investigator: Zachariah DeFilipp, MD — Massachusetts General Hospital
• Study coordinator: Zachariah DeFilipp, MD

Conditions Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; Stem Cell Leukemia