Inqovi Maintenance Therapy for Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia

Not currently recruiting at 1 trial location

Overseen By Zachariah DeFilipp, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Massachusetts General Hospital

Disqualifiers: Prior transplants, Other malignancies, Hepatitis, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a drug called Inqovi in preventing the return of myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) after a stem cell transplant. Inqovi combines two drugs, decitabine and cedazuridine, and the study explores different doses to identify the most effective one. Individuals diagnosed with MDS or CMML who have undergone a stem cell transplant might be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to contribute to groundbreaking research.

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.

Is there any evidence suggesting that Inqovi is likely to be safe for humans?

Research has shown that Inqovi, a combination of the drugs decitabine and cedazuridine, has been studied for its safety in treating myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). In past studies, patients generally tolerated Inqovi well. The most common side effects included low blood cell counts, which are expected with this type of treatment. Doctors closely monitor these side effects.

The FDA has already approved Inqovi for treating adults with MDS, indicating trust in its safety for this use. This approval means it underwent thorough testing and demonstrated an acceptable safety profile in wider use. While any treatment can have side effects, existing data provides insight into Inqovi's safety in people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for myelodysplastic syndrome and chronic myelomonocytic leukemia, which typically includes treatments like azacitidine or conventional decitabine, Inqovi is a combination of decitabine and cedazuridine. This combination allows for oral administration, which is more convenient than traditional intravenous options. Cedazuridine helps prevent the breakdown of decitabine in the gut, potentially enhancing its effectiveness and making treatment more accessible. Researchers are excited about Inqovi because it could offer a more patient-friendly option without compromising the potency of the treatment.

What evidence suggests that Inqovi might be an effective treatment for myelodysplastic syndrome or chronic myelomonocytic leukemia?

Research has shown that the drug Inqovi, which combines decitabine and cedazuridine, may help treat myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML). In studies, patients taking Inqovi lived for an average of 31.7 months. The treatment also achieved a 62% success rate, with many patients experiencing positive effects. Inqovi is convenient because it is taken as a pill, which can help patients maintain a better quality of life while managing these conditions. Although more research is needed, these results suggest that Inqovi could effectively reduce the recurrence of MDS and CMML. Participants in this trial will receive Inqovi in different dosing schedules to further evaluate its effectiveness and safety. ^{1 6 7 8 9}

Who Is on the Research Team?

Zachariah DeFilipp, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

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

Exclusion Criteria

Breastfeeding women

Uncontrolled intercurrent illness that would limit compliance with study requirements

I do not have any untreated infections.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Inqovi

Trial Overview The 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.

How Is the Trial Designed?

Group I: Recommended Phase 2 Dose Expansion (RP2S) Inqovi Experimental Treatment 1 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 Inqovi Experimental Treatment 1 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

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

Published Research Related to This Trial

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Decitabine and Cedazuridine Tablets for Myelodysplastic Syndromes. Kim, N., Norsworthy, KJ., Subramaniam, S., et al.[2023]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cedazuridine/decitabine: from preclinical to clinical development in myeloid malignancies. Patel, AA., Cahill, K., Saygin, C., et al.[2023]

Decitabine/cedazuridine (DEC-C) is the first oral hypomethylating agent approved in Canada for treating myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML), showing a median overall survival of 21.6 months in a real-world study of 769 patients.

The treatment demonstrated a median progression-free survival of 10.7 months, indicating its potential as an effective and convenient alternative to traditional parenteral therapies, especially for older patients with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decitabine/Cedazuridine in the Management of Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia in Canada. Yun, JP., Ding, PQ., Dolley, A., 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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of cedazuridine/decitabine in the management of myelodysplastic syndrome and chronic myelomonocytic leukemia. Thota, S., Oganesian, A., Azab, M., et al.[2021]

The phase 2 study found that oral cedazuridine/decitabine (100 mg/35 mg) provided similar systemic exposure and DNA demethylation compared to standard IV decitabine (20 mg/m2) in patients with myelodysplastic syndromes or chronic myelomonocytic leukemia, indicating comparable efficacy.

Clinical responses were observed in 60% of patients, with 21% achieving a complete response, while the most common serious side effects included neutropenia (46%) and thrombocytopenia (38%), highlighting the treatment's safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral cedazuridine/decitabine for MDS and CMML: a phase 2 pharmacokinetic/pharmacodynamic randomized crossover study. Garcia-Manero, G., Griffiths, EA., Steensma, DP., et al.[2021]

The fixed-dose oral combination of decitabine and cedazuridine (Inqovi®) has been approved for treating myelodysplastic syndromes (MDS) and chronic myelomonocytic leukaemia (CMML), enhancing the oral bioavailability of decitabine through the inhibition of cytidine deaminase by cedazuridine.

Decitabine is already an established treatment for MDS and CMML, and the combination therapy has shown promise in ongoing clinical studies for other cancers like acute myeloid leukaemia (AML), glioma, and solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decitabine/Cedazuridine: First Approval. Dhillon, S.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10528038/

Decitabine/Cedazuridine in the Management of ... The management of myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) is limited and remains an unmet need.

2. inqovi.com inqovi.com/hcp/efficacy-and-safety

Efficacy & Safety | INQOVI® (decitabine and cedazuridine) ... See INQOVI ASCERTAIN clinical trial data, such as overall survival, progression, and safety profile. See full Safety Information.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04980404

Inqovi Maintenance Therapy in Myeloid Neoplasms This research is being done to see if the drug Inqov is effective in reducing the chance of myelodysplastic syndrome (MDS) or chronic myelomonocytic ...

4. onclive.com onclive.com/view/oral-decitabine-cedazuridine-is-a-game-changer-for-mds-and-cmml-treatment

Oral Decitabine-Cedazuridine Is a Game Changer for MDS ... The oral formulation of decitabine-cedazuridine helps empower patients with MDS or CMML to maintain their quality of life from the comfort ...

5. taihooncology.com taihooncology.com/us/news/2021-09-23_astex_press_release_astx727_mos_data_presented_at_mds_international_symposium/

Astex Pharmaceuticals Presents Overall Survival Data ... Study achieved median overall survival of 31.7 months; Updated efficacy data demonstrated an overall response rate of 62%, ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2020/212576s000lbl.pdf

INQOVI® (decitabine and cedazuridine) tablets, for oral use Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia. The safety of INQOVI was evaluated in a pooled safety population that includes patients enrolled ...

7. inqovi.com inqovi.com/

INQOVI® (decitabine and cedazuridine) tablets | MDS Treatment INQOVI is a prescription medicine used to treat adults with myelodysplastic syndromes (MDS), including chronic myelomonocytic leukemia (CMML).

8. inqovi.com inqovi.com/hcp

INQOVI® (decitabine and cedazuridine) Official HCP Website INQOVI is indicated for treatment of adult patients with myelodysplastic syndromes (MDS). See full Safety Info.

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40524338/

Efficacy and safety of oral decitabine/cedazuridine in the ... This analysis described the use of decitabine/cedazuridine in CMML from consecutive, prospective, randomised trials and illustrated a median survival of nearly ...