NIH Clinical Center Search the Studies: Study Number, Study Title

Protocol Details

A Phase I/II Trial of Eltanexor (KPT-8602) with Inqovi (Decitabine-Cedazuridine) in High-Risk Myelodysplastic Syndromes

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

001541-C

Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18 Years
Max Age: 120 Years

Referral Letter Required

No

Population Exclusion(s)

Fetuses;
Children;
Pregnant Women

Keywords

Acute Myeloid Leukemia;
hypomethylating agents;
Allogeneic Hematopoietic Stem Cell Transplantation

Recruitment Keyword(s)

None

Condition(s)

Myelodysplastic Syndromes

Investigational Drug(s)

Eltanexor
Decitabine and Cedazuridine

Investigational Device(s)

None

Intervention(s)

Drug: KPT-8602
Drug: Inqovi

Supporting Site

National Cancer Institute

Background:

Myelodysplastic syndromes (MDS) are diseases that affect the bone marrow. They can inhibit the blood formation process and reduce blood cell counts. High-risk MDS can lead to leukemia. People with high-risk MDS have a low survival rate. Better treatments are needed.

Objective:

To test a study drug (KPT-8602), combined with another drug (Inqovi), in people with MDS.

Eligibility:

Adults aged 18 years and older with high-risk MDS that did not respond to treatment.

Design:

Participants will be screened. They will have a physical exam. They will have blood and urine tests and tests of their heart function. They may have a bone marrow biopsy: Their hip will be numbed; then a needle will be inserted to draw out a sample of soft tissue from inside the bone. They will answer questions about their quality of life. Genetic tests may be performed.

KPT-8602 and Inqovi are both tablets taken by mouth. Participants will take these drugs at home on a 28-day cycle. They will take Inqovi once a day on days 1 to 5. They will take KPT-8602 on a schedule assigned by the researcher. Participants will be given a drug diary to record each dose.

Participants will visit the clinic for an exam at least once in each cycle. Some tests, including the bone marrow biopsy, may be repeated.

Participant will continue treatment for at least 6 cycles. If their disease improves, they may continue taking the drugs after 6 cycles.

Participants will have follow-up visits at the clinic for about 8 years.

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Eligibility

INCLUSION CRITERIA:

1.Participants must have histologically or cytologically confirmed MDS by the Laboratory of Pathology, NCI- according to 2016 WHO criteria AND:

-Cohort 1 (Phase 1) & 2 (Phase 2): have HR-MDS (IPSS-R > 3.5) with inadequate response to hypomethylating agent (HMA) therapy [(received >= 4 cycles of the standard dose (35 mg decitabine and 100 mg cedazuridine) without prior dose reductions, with failure to achieve at least a PR or experienced disease progression prior to completing 4 cycles)

2. Age >=18 years

3. ECOG performance status <= 2 (Karnofsky >= 60%,)

4. Participants must have adequate organ and marrow function as defined below:

-total bilirubin <= 1.5 X institutional upper limit of normal

OR

<= 3 X institutional upper limit of normal in participants with Gilbert s syndrome (except for participants with increased bilirubin levels attributed to intramedullary hemolysis, which will be allowable)

-AST(SGOT)/ALT(SGPT) <= 3 X institutional upper limit of normal

OR

<= 5 X institutional upper limit of normal if related to MDS-specific cause

-creatinine clearance >= 60 mL/min

- QTc(F) <= 470 ms

5. Females of child-bearing potential (FOCP) must have a negative serum test at screening. FOCP is defined as the following:

- Has not undergone a hysterectomy, tubal ligation, or bilateral oophorectomy

-Has not been naturally postmenopausal for at least 24 consecutive months (i.e.,has had menses at any time in the preceding 24 consecutive months).

6. Females of childbearing potential (FOCP) and males of child-fathering potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) unless they have had a prior vasectomy, hysterectomy, or bilateral oophorectomy, prior to study entry, for the duration of study participation, and for at least 6 months after last dose of HMA.

7. Breastfeeding participants must be willing to discontinue breastfeeding from study treatment initiation through 30 days after the last administration of study drug

8. Any prior therapy must have been completed >4 weeks or, if known, >= 5 half-lives of the prior agent (whichever is shorter) prior to treatment (with a minimum of 1 week between prior therapy and study treatment). Note: This does not apply to prior HMA therapy if that therapy involves Inqovi

9. Ability to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

1. Participants with platelet transfusion-refractory thrombocytopenia, with inability to keep platelet threshold above 10K/mcL with transfusions or those with ongoing or uncontrolled hemorrhagic complications.

2. Participants with clinically significant neutropenia, defined as ANC <100 cells/mcL with frequent hospitalizations for infection (average > 1 hospitalization per month in the past 6 months).

3. Participants on treatment with a myeloid growth factor (e.g., G-CSF) within 14 days prior to initiation of study treatment.

4. History of allergic reactions attributed to compounds of similar chemical or biologic composition to HMAs or other agents used in study.

5. Uncontrolled intercurrent illness evaluated by history, physical exam, and chemistries or

situations that would limit compliance with study requirements, interpretation of results or that could increase risk to the participant

6. Participants with the following cardiac conditions: symptomatic congestive heart failure,

unstable angina pectoris, or cardiac arrhythmia as assessed by electrocardiogram (ECG).

7. Pregnancy (confirmed with Beta-HCG serum or urine pregnancy test performed in females of childbearing potential at screening)

8. Presence of any other malignancy (except basal and squamous cell carcinoma of the skin, or stable chronic cancers on hormone or targeted therapy) for which participant received systemic anticancer treatment (except maintenance therapy) within 24 months prior to treatment.

9. Participants with active/uncontrolled Hepatitis B

10. Participants with active/uncontrolled Hepatitis C

11. Participants with active/uncontrolled HIV infection or AIDS.

12. Participants currently taking contraindicated medications for HIV, Hepatitis B, or Hepatitis C disease control


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Citations:

Not Provided

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Contacts:

Principal Investigator

Referral Contact

For more information:

Steven Z. Pavletic, M.D.
National Cancer Institute (NCI)
NIHBC 10 - CRC BG RM 4-3130
10 CENTER DR
BETHESDA MD 20892
(240) 760-6174
sp326h@nih.gov

Rebecca Alexander
National Cancer Institute (NCI)
National Institutes of Health
Building 10
Room 4-3152
10 Center Drive
Bethesda, Maryland 20892
(240) 781-4037
rebecca.alexander@nih.gov

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
1-888-NCI-1937

Clinical Trials Number:

NCT05918055

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NIH Clinical Center Search the Studies: Study Number, Study Title

Protocol Details

A Phase I/II Trial of Eltanexor (KPT-8602) with Inqovi (Decitabine-Cedazuridine) in High-Risk Myelodysplastic Syndromes

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

001541-C

Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18 Years
Max Age: 120 Years

Referral Letter Required

No

Population Exclusion(s)

Fetuses;
Children;
Pregnant Women

Keywords

Acute Myeloid Leukemia;
hypomethylating agents;
Allogeneic Hematopoietic Stem Cell Transplantation

Recruitment Keyword(s)

None

Condition(s)

Myelodysplastic Syndromes

Investigational Drug(s)

Eltanexor
Decitabine and Cedazuridine

Investigational Device(s)

None

Intervention(s)

Drug: KPT-8602
Drug: Inqovi

Supporting Site

National Cancer Institute

Background:

Myelodysplastic syndromes (MDS) are diseases that affect the bone marrow. They can inhibit the blood formation process and reduce blood cell counts. High-risk MDS can lead to leukemia. People with high-risk MDS have a low survival rate. Better treatments are needed.

Objective:

To test a study drug (KPT-8602), combined with another drug (Inqovi), in people with MDS.

Eligibility:

Adults aged 18 years and older with high-risk MDS that did not respond to treatment.

Design:

Participants will be screened. They will have a physical exam. They will have blood and urine tests and tests of their heart function. They may have a bone marrow biopsy: Their hip will be numbed; then a needle will be inserted to draw out a sample of soft tissue from inside the bone. They will answer questions about their quality of life. Genetic tests may be performed.

KPT-8602 and Inqovi are both tablets taken by mouth. Participants will take these drugs at home on a 28-day cycle. They will take Inqovi once a day on days 1 to 5. They will take KPT-8602 on a schedule assigned by the researcher. Participants will be given a drug diary to record each dose.

Participants will visit the clinic for an exam at least once in each cycle. Some tests, including the bone marrow biopsy, may be repeated.

Participant will continue treatment for at least 6 cycles. If their disease improves, they may continue taking the drugs after 6 cycles.

Participants will have follow-up visits at the clinic for about 8 years.

--Back to Top--

Eligibility

INCLUSION CRITERIA:

1.Participants must have histologically or cytologically confirmed MDS by the Laboratory of Pathology, NCI- according to 2016 WHO criteria AND:

-Cohort 1 (Phase 1) & 2 (Phase 2): have HR-MDS (IPSS-R > 3.5) with inadequate response to hypomethylating agent (HMA) therapy [(received >= 4 cycles of the standard dose (35 mg decitabine and 100 mg cedazuridine) without prior dose reductions, with failure to achieve at least a PR or experienced disease progression prior to completing 4 cycles)

2. Age >=18 years

3. ECOG performance status <= 2 (Karnofsky >= 60%,)

4. Participants must have adequate organ and marrow function as defined below:

-total bilirubin <= 1.5 X institutional upper limit of normal

OR

<= 3 X institutional upper limit of normal in participants with Gilbert s syndrome (except for participants with increased bilirubin levels attributed to intramedullary hemolysis, which will be allowable)

-AST(SGOT)/ALT(SGPT) <= 3 X institutional upper limit of normal

OR

<= 5 X institutional upper limit of normal if related to MDS-specific cause

-creatinine clearance >= 60 mL/min

- QTc(F) <= 470 ms

5. Females of child-bearing potential (FOCP) must have a negative serum test at screening. FOCP is defined as the following:

- Has not undergone a hysterectomy, tubal ligation, or bilateral oophorectomy

-Has not been naturally postmenopausal for at least 24 consecutive months (i.e.,has had menses at any time in the preceding 24 consecutive months).

6. Females of childbearing potential (FOCP) and males of child-fathering potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) unless they have had a prior vasectomy, hysterectomy, or bilateral oophorectomy, prior to study entry, for the duration of study participation, and for at least 6 months after last dose of HMA.

7. Breastfeeding participants must be willing to discontinue breastfeeding from study treatment initiation through 30 days after the last administration of study drug

8. Any prior therapy must have been completed >4 weeks or, if known, >= 5 half-lives of the prior agent (whichever is shorter) prior to treatment (with a minimum of 1 week between prior therapy and study treatment). Note: This does not apply to prior HMA therapy if that therapy involves Inqovi

9. Ability to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

1. Participants with platelet transfusion-refractory thrombocytopenia, with inability to keep platelet threshold above 10K/mcL with transfusions or those with ongoing or uncontrolled hemorrhagic complications.

2. Participants with clinically significant neutropenia, defined as ANC <100 cells/mcL with frequent hospitalizations for infection (average > 1 hospitalization per month in the past 6 months).

3. Participants on treatment with a myeloid growth factor (e.g., G-CSF) within 14 days prior to initiation of study treatment.

4. History of allergic reactions attributed to compounds of similar chemical or biologic composition to HMAs or other agents used in study.

5. Uncontrolled intercurrent illness evaluated by history, physical exam, and chemistries or

situations that would limit compliance with study requirements, interpretation of results or that could increase risk to the participant

6. Participants with the following cardiac conditions: symptomatic congestive heart failure,

unstable angina pectoris, or cardiac arrhythmia as assessed by electrocardiogram (ECG).

7. Pregnancy (confirmed with Beta-HCG serum or urine pregnancy test performed in females of childbearing potential at screening)

8. Presence of any other malignancy (except basal and squamous cell carcinoma of the skin, or stable chronic cancers on hormone or targeted therapy) for which participant received systemic anticancer treatment (except maintenance therapy) within 24 months prior to treatment.

9. Participants with active/uncontrolled Hepatitis B

10. Participants with active/uncontrolled Hepatitis C

11. Participants with active/uncontrolled HIV infection or AIDS.

12. Participants currently taking contraindicated medications for HIV, Hepatitis B, or Hepatitis C disease control


--Back to Top--

Citations:

Not Provided

--Back to Top--

Contacts:

Principal Investigator

Referral Contact

For more information:

Steven Z. Pavletic, M.D.
National Cancer Institute (NCI)
NIHBC 10 - CRC BG RM 4-3130
10 CENTER DR
BETHESDA MD 20892
(240) 760-6174
sp326h@nih.gov

Rebecca Alexander
National Cancer Institute (NCI)
National Institutes of Health
Building 10
Room 4-3152
10 Center Drive
Bethesda, Maryland 20892
(240) 781-4037
rebecca.alexander@nih.gov

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
1-888-NCI-1937

Clinical Trials Number:

NCT05918055

--Back to Top--