22 Participants Needed

Inqovi Maintenance Therapy for Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia

Recruiting at 1 trial location
Zachariah DeFilipp - Boston ...
Overseen ByZachariah DeFilipp, MD
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: Massachusetts General Hospital
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Approved in 2 JurisdictionsThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

This trial is testing Inqovi, a drug that combines decitabine and cedazuridine, to see if it can prevent relapse in patients with MDS or CMML after a stem cell transplant. Decitabine stops cancer cells from growing, and cedazuridine helps decitabine stay effective longer. The study aims to find the safest dose for these patients. Decitabine has shown effectiveness in various blood-related cancers.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Inqovi (Decitabine-Cedazuridine) for Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia?

Inqovi, a combination of decitabine and cedazuridine, has been shown to be effective for treating Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML) in clinical trials. Studies demonstrated that the drug's effectiveness is similar to intravenous decitabine, with a complete remission rate of around 21% and a median remission duration of 7.5 to 8.7 months.12345

Is Inqovi (Decitabine-Cedazuridine) safe for humans?

Inqovi, a combination of decitabine and cedazuridine, has been studied for safety in humans, showing similar safety profiles to intravenous decitabine. Common serious side effects include low white blood cell counts (neutropenia), low platelet counts (thrombocytopenia), and fever with low white blood cell counts (febrile neutropenia).12346

How is the drug Inqovi different from other treatments for myelodysplastic syndrome and chronic myelomonocytic leukemia?

Inqovi is unique because it combines decitabine, a drug that modifies DNA to stop cancer cell growth, with cedazuridine, which helps the body absorb decitabine when taken orally. This allows patients to take the treatment as a pill instead of needing intravenous infusions, making it more convenient.12346

Research Team

ZD

Zachariah DeFilipp, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

This trial is for adults with myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) who are undergoing their first stem cell transplant. They must have a matched donor, good organ function, and no severe heart issues or infections. Women of childbearing age need a negative pregnancy test and agree to use birth control.

Inclusion Criteria

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)
I am scheduled for my first stem cell transplant from a donor.
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
See 6 more

Exclusion Criteria

Breastfeeding women
Uncontrolled intercurrent illness that would limit compliance with study requirements
I do not have any untreated infections.
See 8 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Initial group of 3 participants will receive Inqovi on days 1-3 of a 42 day cycle to determine dose-limiting toxicity

6 weeks
1 visit every 6 weeks

Recommended Phase 2 Dose Expansion

Once the Recommended Phase 2 Dose Expansion is established, 10 additional participants will receive Inqovi on days 1-3 of a 28 day cycle

4 weeks per cycle
1 visit every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Treatment Details

Interventions

  • Inqovi
Trial OverviewThe trial tests Inqovi as maintenance therapy post-stem cell transplant to prevent MDS/CMML relapse. Inqovi combines decitabine and cedazuridine, aiming to reduce the chance of disease returning after standard treatment.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Recommended Phase 2 Dose Expansion (RP2S) InqoviExperimental Treatment1 Intervention
Once the Recommended Phase 2 Dose Expansion (RP2S) is established, 10 additional participants will be enrolled and receive Inqovi (decitabine/cedazuridine) on days 1-3 of a 28 day study cycle.
Group II: Dose Escalation InqoviExperimental Treatment1 Intervention
Study will follow a standard '3+3' dose escalation design: * Initial group of 3 participants will receive Inqovi (decitabine/cedazuridine) on days 1-3 of a 42 day cycle/dose-limiting toxicity (DLT) period. * Additional enrollment, dosage and study cyles will be determined by number of dose-limiting toxicity (DLT) that occur in initial group

Find a Clinic Near You

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials
3,066
Recruited
13,430,000+

Taiho Oncology, Inc.

Industry Sponsor

Trials
79
Recruited
12,700+

Tim Whitten

Taiho Oncology, Inc.

Chief Executive Officer since 2018

MBA and Pharmacy degree

Harold Keer

Taiho Oncology, Inc.

Chief Medical Officer

MD, PhD

Findings from Research

The combination of oral cedazuridine and decitabine (C-DEC) has been shown to have a similar pharmacokinetic and pharmacodynamic profile to parenteral decitabine, making it a promising alternative for treating higher-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML).
Phase 2 and phase 3 clinical trials confirmed the bioequivalence of C-DEC to parenteral decitabine, leading to FDA approval for its use in intermediate/high-risk MDS and CMML, highlighting its efficacy and safety as an oral treatment option.
Cedazuridine/decitabine: from preclinical to clinical development in myeloid malignancies.Patel, AA., Cahill, K., Saygin, C., et al.[2023]
A new oral drug combination, DEC-cedazuridine (C-DEC), has been developed to provide a more convenient treatment option for patients with myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML), which traditionally required lengthy parenteral therapies.
C-DEC has been approved by major health authorities, including the US FDA, for patients with newly diagnosed or previously treated intermediate or high-risk MDS and CMML, indicating its safety and potential efficacy in managing these complex disorders.
Role of cedazuridine/decitabine in the management of myelodysplastic syndrome and chronic myelomonocytic leukemia.Thota, S., Oganesian, A., Azab, M., et al.[2021]
Inqovi, a combination of decitabine and cedazuridine, was approved by the FDA for treating myelodysplastic syndromes (MDS) based on a phase III study involving 133 adults, showing similar effectiveness to intravenous decitabine.
The treatment demonstrated a complete remission rate of 21% in one study and 18% in another, with a median duration of remission lasting around 7.5 to 8.7 months, while adverse reactions were consistent with those seen in IV decitabine.
FDA Approval Summary: Decitabine and Cedazuridine Tablets for Myelodysplastic Syndromes.Kim, N., Norsworthy, KJ., Subramaniam, S., et al.[2023]

References

Cedazuridine/decitabine: from preclinical to clinical development in myeloid malignancies. [2023]
Role of cedazuridine/decitabine in the management of myelodysplastic syndrome and chronic myelomonocytic leukemia. [2021]
FDA Approval Summary: Decitabine and Cedazuridine Tablets for Myelodysplastic Syndromes. [2023]
Decitabine/Cedazuridine: First Approval. [2021]
Decitabine/Cedazuridine in the Management of Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia in Canada. [2023]
Oral cedazuridine/decitabine for MDS and CMML: a phase 2 pharmacokinetic/pharmacodynamic randomized crossover study. [2021]