Relapsed/Refractory Multiple Myeloma (RRMM)Phase 1/2NCT02649790
Study of the Safety, Tolerability and Efficacy of KPT-8602 in Participants With Relapsed/Refractory Cancer Indications
A Phase 1/2 study testing KPT-8602, ASTX727 and Dexamethasone in people with Relapsed/Refractory Multiple Myeloma (RRMM) and Metastatic Colorectal Cancer (mCRC), run by Karyopharm Therapeutics Inc at 46 sites in 5 countries.
Trial summary
This is a first-in-human, multi-center, open-label clinical study with separate dose escalation (Phase 1) and expansion (Phase 2) stages to assess preliminary safety, tolerability, and efficacy of the second generation oral XPO1 inhibitor KPT-8602 in participants with relapsed/refractory multiple myeloma (MM)… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed/Refractory Multiple Myeloma (RRMM), Metastatic Colorectal Cancer (mCRC), Metastatic Castration-Resistant Prostate Cancer (mCRPC)
- What is being tested?
- KPT-8602, ASTX727 and Dexamethasone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 277 participants
- Where
- 46 sitesin 5 countries
- Study dates
- Jan 2016to 23 Dec 2024
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent signed prior to any screening procedures and in accordance with federal, local, and institutional guidelines.
- Age ≥ 18 years.
- Adequate hepatic function:
- total bilirubin ≤ 2 times the upper limit of normal (ULN) (except participants with Gilbert's syndrome [hereditary indirect hyperbilirubinemia] who must have a total bilirubin of ≤ 4 times ULN),
- aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times ULN (except participants with known liver involvement of their tumor who must have their AST and ALT ≤ 5.0 times ULN).
- Adequate renal function: estimated creatinine clearance of ≥ 30 mL/min, calculated using the formula of Cockcroft and Gault (140-Age) × Mass (kg)/(72 × creatinine mg/dL); multiply by 0.85 if female.
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- Contraception:
- Participants with RRMM, CRC, RR high-risk MDS (Part F Phase 2), and AML (Part H): Female participants of child-bearing potential must agree to use dual methods of contraception (including 1 highly effective and 1 effective method of contraception) and have a negative serum test at Screening, and male participants must use an effective barrier method of contraception if sexually active. For both male and female participants, effective methods of contraception must be used throughout the study and for 3 months following the last dose
- Participants with RR mCRPC: Participants must use an effective barrier method of contraception if sexually active. Effective methods of contraception must be used throughout the study and for 3 months following the last dose
- Participants with newly diagnosed intermediate/high-risk MDS (Part G): Female participants of child-bearing potential must agree to use dual methods of contraception (including 1 highly effective and 1 effective method of contraception) and have a negative serum pregnancy test at Screening, and male participants must use an effective barrier method of contraception if sexually active. For both male and female participants, effective methods of contraception must be used throughout the study and for 6 months following the last dose
- INDICATION-SPECIFIC INCLUSION CRITERIA
- Relapsed/Refractory Multiple Myeloma (Parts A1, A2, and B - Completed):
- Symptomatic, histologically confirmed MM and evidence of disease progression, based on IMWG guidelines.
- Participants must have measurable disease as defined by at least 1 of the following:
- Serum M-protein ≥ 0.5 g/dL by serum protein electrophoresis (SPEP) or for immunoglobulin (Ig) A myeloma, by quantitative IgA. If SPEP is felt to be unreliable for routine M-protein measurement (e.g., for participants with IgA MM), then quantitative Ig levels by nephelometry; or
- Urinary M-protein excretion at least 200 mg/24 hours; or
- Serum free light chain (FLC) whereby the involved light chain measures ≥ 10 mg/dL and with an abnormal ratio.
- Previously treated with ≥ 3 prior regimens (lines of therapy) that included at least 1 of each of the following: an immunomodulatory drug, a proteasome inhibitor, and a steroid.
- MM refractory to the participants most recent anti-MM regimen.
- Participants receiving hematopoietic growth factor support including erythropoietin, darbepoetin, granulocyte-colony stimulating factor, granulocyte macrophage-colony stimulating factor, and platelet stimulators can continue to do so, but must be transfusion independent for at least 1 week prior to Cycle 1 Day 1 (C1D1) in the study.
- Adequate hematopoietic function: total white blood cell (WBC) count ≥ 1500/mm^3, absolute neutrophil count (ANC) ≥ 800/mm^3, hemoglobin (Hb) ≥ 8.0 g/dL, and platelet count ≥ 75,000/mm^3.
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤1.
- Life expectancy of ≥ 4 months.
- Relapsed/Refractory Colorectal Cancer (Part C - Completed):
- Histological or cytological documentation of adenocarcinoma of the colon or rectum.
- Measurable disease by RECIST v1.1.
- Metastatic disease not suitable for upfront curative-intent surgery.
- Participants with site-defined KRAS status (wild-type or mutant) from a fresh or archival tumor biopsy prior to enrollment. All participants must be willing to have fresh biopsies to obtain tumor tissue for biomarker analysis.
- Documented evidence of progressive disease according to RECIST v1.1.
- Prior treatment (with completion of a course of therapy, or to disease progression or intolerability) with each of the following:
- Fluoropyrimidine-, oxaliplatin-, irinotecan-based chemotherapies (e.g., FOLFOX and/or FOLFIRI)
- if KRAS wild-type, an anti-EGFR therapy,
- Prior third line treatment with regorafenib or TAS-102, will be assessed on an individual basis,
- Note: The requirement for prior third line regorafenib will be assessed on an individual basis by the investigator in consultation with the Karyopharm Medical Monitor
- Radiation and surgery are not considered as prior anticancer regimens
- Participants should not be transfusion dependent.
- Adequate hematopoietic function: ANC ≥ 1000/mm^3, hemoglobin (Hb) ≥ 9.0 g/dL, and platelet count ≥ 100,000/mm^3.
- ECOG performance status of ≤ 1.
- Life expectancy of ≥ 4 months.
- Relapsed/Refractory Metastatic Castration-resistant Prostate Cancer (Parts D and E - Completed):
- Histologically confirmed adenocarcinoma of the prostate with archival tumor tissue available for molecular analyses. If the participants does not have a prior histological diagnosis, then a fresh biopsy at Screening may be used for this purpose.
- Optional: All participants will be asked to have fresh biopsies to obtain tumor tissue for biomarker analysis.
- Surgically or medically castrated, with testosterone levels of < 50 ng/dL (< 2.0 nM). If the participant is being treated with luteinizing hormone-releasing hormone (LHRH) agonists (participants who have not undergone orchiectomy), and participants must have shown to progress on this.
- Documented mCRPC progression as assessed by the Investigator with 1 of the following:
- Prostate-specific antigen (PSA) progression defined by a minimum of 3 rising PSA levels (at approximately Day -30 and approximately Day -45) with an interval of > 1 week between each determination. The PSA values at the Screening visit should be > 2 μg/L (> 2 ng/mL); participants on systemic glucocorticoids for control of symptoms must have documented PSA progression by Prostate Cancer Working Group 3 (PCWG3) while on systemic glucocorticoids prior to commencing C1D1 of treatment.
- Radiographic progression of soft tissue disease by modified RECIST criteria 1.1 or of bone metastasis with 2 or more documented new bone lesions on a bone scan with or without PSA progression.
- Initial response (per modified PCWG3 Guidelines) to second generation anti-hormonal therapy (examples: abiraterone, enzalutamide, TAK 700), but later relapsed. Disease relapse would be defined as progressive disease at the time of entry per inclusion criterion 24.
- Zero to 2 previous taxane-based chemotherapy regimens. If docetaxel chemotherapy is used more than once, this will be considered as 1 regimen. Participants may have had prior exposure to cabazitaxel treatment. Participants may be taxane naïve.
- At least 2 weeks from completion of any radiotherapy including a single fraction of radiotherapy for the purposes of palliation (confined to 1 field) is permitted.
- Participants should not be transfusion dependent.
- Albumin > 2.5 g/dL.
- Adequate hematopoietic function: ANC ≥ 1000/mm^3, hemoglobin (Hb) ≥ 9.0 g/dL, and platelet count ≥ 100,000/mm^3.
- Part E only: Participants currently receiving treatment with abiraterone and appropriate to continue in the opinion of the Investigator. Participants must also have been on and continue on a stable dose of corticosteroids (prednisone or dexamethasone) for 30 days prior to C1D1.
- ECOG performance status of ≤ 1.
- Life expectancy of ≥ 4 months.
- RR High-risk Myelodysplastic Syndrome (Part F Phase 2):
- Documented diagnosis of MDS with 5% to 19% myeloblasts in the bone marrow (2016 WHO classification).
- The marrow histopathology must be documented by recent bone marrow biopsy (within 30 days prior to C1D1).
- IPSS-R: intermediate, high- or very-high-risk MDS.
- RR MDS defined as having one of the following:
- ≥ 2 cycles of hypomethylating agents (azacitidine and/or decitabine, ASTX727, or experimental agents) with clear PD (pancytopenia with ≥ 50% increase in bone marrow blasts) or participant progressed to a higher risk category of MDS OR
- ≥ 4 cycles of HMA therapy with SD/lack of improvement (no CR/mCR/PR/HI) per International Working Group (IWG) 2006 criteria, or intolerance to treatment (≥ 6 cycles of azacitidine if required per local standard of care guidelines to establish lack of improvement/response to azacitidine) OR
- Relapse or disease progression after an initial response to HMA (CR/mCR/PR/HI) per IWG 2006 criteria.
- ECOG performance status of < 2.
- Prior to enrolling a participant with imminent risk of AML transformation (per opinion of the Investigator) or for participants with RAEB-2 MDS, the Medical Monitor must be contacted.
- Newly Diagnosed Intermediate/High-risk Myelodysplastic Syndrome (Part G):
- Documented diagnosis of MDS with 5% to 19% myeloblasts in the bone marrow (2016 WHO classification)
- The marrow histopathology must be documented in bone marrow biopsy (within 30 days prior to C1D1)
- IPSS-R intermediate, high- or very-high-risk MDS.
- No prior therapy for HR-MDS (up to one prior cycle of an HMA is allowed). Prior supportive care in the form of transfusions, growth factors, etc. is permitted.
- ECOG performance status of < 2.
- AML Maintenance (Post-alloSCT) Therapy (Part H):
- Participants with de novo AML or AML secondary to prior myelodysplastic disease.
- Received one allogeneic SCT (alloSCT).
- Participants must be able to start study treatment between 40 and 100 days following alloSCT
- Participants must be CR/CRi at the time of study enrollment, and must meet at least one of the following criteria:
- MRD positive at time of enrollment
- Evidence of disease pre-alloSCT (received alloSCT while not in CR/CRi, or while MRD positive)
- In CR2 or greater pre-alloSCT (regardless of MRD status)
- Adverse cytogenetics at time of diagnosis (regardless of MRD status) per ELN 2017 criteria
- Adequate engraftment within 14 days prior to starting study therapy: absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L without daily use of myeloid growth factor, and platelet count 75 x 10^9/L without platelet transfusion within 1 week.
- ECOG performance status of ≤ 2
Who cannot join
- Participants in All Parts of the Study:
- Female participants who are pregnant or lactating.
- Major surgery within 4 weeks before C1D1.
- Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
- Unstable angina or acute myocardial infarction ≤ 3 months prior to C1D1
- Clinically significant heart disease (e.g., symptomatic congestive heart failure [e.g., > NYHA Class 2]; uncontrolled arrhythmia, or hypertension; history of labile hypertension or poor compliance with an antihypertensive regimen)
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- Uncontrolled active severe systemic infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to C1D1.
- Participants with known symptomatic brain metastasis are not suitable for enrollment. Participants with asymptomatic, stable, treated brain metastases are eligible for study entry
- Participants with a known history of human immunodeficiency virus (HIV); HIV testing is not required as part of this study
- Known, active hepatitis A, B, or C infection; or known to be positive for HCV RNA or HBsAg (HBV surface antigen)
- Prior malignancies:
- Participants with adequately resected basal or squamous cell carcinoma of the skin, or adequately resected carcinoma in situ (i.e., cervix) may enroll irrespective of the time of diagnosis
- Participants with relapsed/refractory MM, CRC, and mCRPC only: Prior malignancies which may interfere with the interpretation of the study. Cancer treated with curative intent < 5 years previously will not be allowed unless approved by the Sponsor. Cancer treated with curative intent > 5 years previously and without evidence of recurrence will be allowed.
- For participants in Arms F Phase 2, G, and H: Prior malignancy is not an exclusion
- Participants with gastrointestinal tract disease (or uncontrolled vomiting or diarrhea) that could interfere with the absorption of eltanexor (or ASTX727 in Part G).
- Serious psychiatric or medical conditions that, in the opinion of the Investigator, could interfere with treatment, compliance, or the ability to give consent.
- Participants unwilling to comply with the protocol including required biopsies and sample collections required to measure disease.
- INDICATION-SPECIFIC EXCLUSION CRITERIA
- Relapsed/Refractory Multiple Myeloma (RRMM) (Parts A1, A2 and B - Completed):
- Time since the last prior therapy for treatment of RRMM:
- Radiation, chemotherapy, immunotherapy or any other anticancer therapy, including investigational anticancer therapy ≤ 2 weeks prior to C1D1
- Palliative steroids for disease related symptoms are allowed up to 3 days prior to C1D1.
- Participants must have recovered or stabilized (≤ Grade 1 or to their baseline) from toxicities related to their previous treatment except for alopecia
- Participants with active graft versus host disease after allogeneic stem cell transplantation. At least 3 months must have elapsed since completion of allogeneic stem cell transplantation.
- Grade > 2 peripheral neuropathy or Grade 2 peripheral neuropathy with pain within 2 weeks prior to C1D1.
- Relapsed/Refractory Colorectal Cancer (Part C - Completed):
- Radiotherapy, chemotherapy, or any other anticancer therapy, including investigational anticancer therapy within 2 weeks prior to Screening. Participants must have recovered from clinically significant toxicities. The site of irradiation should have evidence of progressive disease (new lesions or increase in lesion size) if this is the only site of disease.
- Participants who have been treated with their most recent chemotherapy or investigational drugs ≤21 days or 5 half-lives (whichever is longer) prior to the first dose of study treatment, and/or have any acute toxicities due to prior chemotherapy and/ or radiotherapy that have not resolved to a NCI CTCAE v4.03 Grade 0 or Grade 1 with the exception of chemotherapy induced alopecia and Grade 2 peripheral neuropathy.
- Relapsed/Refractory Metastatic Castration-Resistant Prostate Cancer (Parts D and E - Completed):
- Participants who have been treated with their most recent chemotherapy or investigational drugs ≤ 21 days or 5 half-lives (whichever is longer) prior to the first dose of study treatment, and/or have any acute toxicities due to prior chemotherapy and/ or radiotherapy that have not resolved to a NCI CTCAE v4.03 Grade 0 or Grade 1 with the exception of chemotherapy-induced alopecia and Grade 2 peripheral neuropathy.
- Initiating bisphosphonate therapy or adjusting bisphosphonate dose/regimen within 30 days prior to C1D1. Participants on a stable bisphosphonate or denosumab regimen are eligible and may continue.
- RR High-risk Myelodysplastic Syndrome (Part F Phase 2):
- Very low or low-risk MDS per IPSS-R.
- Evidence of transformation to AML by the World Health Organization (WHO) (≥ 20% blasts in bone marrow or peripheral blood).
- Participants who are significantly below their ideal body weight as judged by the Investigator.
- Any severe GVHD, or organ system dysfunction, which in the Investigator's opinion, could compromise the participant's safety.
- Newly Diagnosed Intermediate/High-risk Myelodysplastic Syndrome (Part G):
- IPSS-R very low or low-risk MDS.
- Evidence of transformation to AML by the WHO (≥ 20% blasts in bone marrow or peripheral blood).
- AML Maintenance (Post-alloSCT) Therapy (Part H):
- Use of any anti-cancer maintenance therapy after alloSCT and prior to starting the study treatment
- Active GVHD Grade 2 or higher.
- Concurrent use of corticosteroids equivalent of prednisone at a dose > 0.5 mg/kg.
Trial locations and contacts
46 sites in 5 countries.
46 sites in 5 countries
United States26 sites
University of New Mexico
Albuquerque, New Mexico, 87131
Rocky Mountain Regional VA Medical Center
Aurora, Colorado, 80045
(USO) Texas Oncology Austin - Midtown
Austin, Texas, 78705
University of Virginia
Charlottesville, Virginia, 22903
(USO) Oncology Hematology Care
Cincinnati, Ohio, 45236
Ohio State University, The James Cancer Hospital and Solove Research Institute
Columbus, Ohio, 43210
(USO) Texas Oncology (Dallas)
Dallas, Texas, 75246
Sarah Cannon Cancer Center - (Colorado Blood Cancer Institute)
Denver, Colorado, 80218
(USO) Virginia Cancer Specialists
Fairfax, Virginia, 22031
Cancer and Hematology Centers of Western Michigan
Grand Rapids, Michigan, 49503
John Theurer Cancer Center at Hackensack UMC
Hackensack, New Jersey, 07601
MD Anderson Cancer Center
Houston, Texas, 77030
Sarah Cannon Cancer Center (HCA Midwest KC)
Kansas City, Missouri, 64132
(USO) Rocky Mountain Cancer Centers
Littleton, Colorado, 80120-4413
David Geffen School of Medicine at UCLA
Los Angeles, California, 90095
Baptist Cancer Center
Memphis, Tennessee, 38120
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Weill Cornell Medical College
New York, New York, 10021
Callahan Cancer Center
North Platte, Nebraska, 69101
Oncology Institute of Hope and Innovation
Pasadena, California, 91105
University of Pennsylvania Abramson Cancer Center Clinical Research Unit
Philadelphia, Pennsylvania, 19104
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
University of Washington
Seattle, Washington, 98109
Moffitt Cancer Center
Tampa, Florida, 33612
(USO) Texas Oncology (Tyler)
Tyler, Texas, 75702
(USO) Compass oncology
Vancouver, Washington, 98684
France7 sites
CHU Nantes
Nantes, 44000
Hôpital Cochin APHP
Paris, 75014
Hôpital Necker
Paris, 75015
Hôpital St Louis
Paris
CHU de Bordeaux
Pessac, 33604
CHU de Tours
Tours, 37044
CHRU de Nancy
Vandœuvre-lès-Nancy, 54500
Spain7 sites
Clínica Universidad de Navarra
Barcelona, 08036
Hospital San Pedro de Alcántara
Cáceres
Clinical Universidad de Navarra (Madrid site)
Madrid, 28027
Hospital 12 de Octubre
Madrid
Hospital Universitario Central Asturias
Oviedo
Hospital Clínic of Barcelona
Pamplona, 31008
Hospital La Fe
Valencia
Canada4 sites
McMaster - Juravinski Cancer Centre
Hamilton, Ontario
MUHC GLEN Site Cedars - Cancer Centre
Montreal, Quebec
Princess Margaret Cancer Center
Toronto, Ontario, M5G 2M9
Princess Margaret Cancer Research
Toronto, Ontario
China2 sites
Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences
Tianjin, Tianjin Municipality, 300041
China, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, 430022
About this study
Official title: A Phase 1/2 Open-Label Study of the Safety, Tolerability and Efficacy of the Selective Inhibitor of Nuclear Export (SINE) Compound Eltanexor (KPT-8602) in Patients With Newly Diagnosed and Relapsed/Refractory Cancer Indications
This is a first-in-human, multi-center, open-label clinical study with separate dose escalation (Phase 1) and expansion (Phase 2) stages to assess preliminary safety, tolerability, and efficacy of the second generation oral XPO1 inhibitor KPT-8602 in participants with relapsed/refractory multiple myeloma (MM), metastatic colorectal cancer (mCRC), metastatic castration resistant prostate cancer (mCRPC), higher risk myelodysplastic syndrome (HRMDS), acute myeloid leukemia (AML) and newly diagnosed intermediate/high-risk MDS.
Dose escalation and dose expansion may be included for all parts of the study as determined by ongoing study results.
- Conditions
- Relapsed/Refractory Multiple Myeloma (RRMM), Metastatic Colorectal Cancer (mCRC), Metastatic Castration-Resistant Prostate Cancer (mCRPC), Higher-Risk Myelodysplastic Syndrome (HR-MDS), Acute Myeloid Leukemia (AML), Newly Diagnosed Intermediate/High-Risk MDS
- Being tested
- KPT-8602, ASTX727, Dexamethasone
- Keywords
- Multiple Myeloma, Karyopharm, KPT-8602, MM, Phase 1, Relapsed/ Refractory Multiple Myeloma, Myelodysplastic Syndrome, MDS, Metastatic Castration-Resistant Prostate Cancer, mCRPC, CRC, Metastatic Colorectal Cancer, AML
- Medical subject headings
- Multiple Myeloma, Colorectal Neoplasms, Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KPT-8602Drug
Also called Eltanexor
Participants will receive KPT-8602 oral tablets.
ASTX727Drug
ASTX727 is a combination drug of 35 mg decitabine and 100 mg cedazuridine.
DexamethasoneDrug
Participants will receive dexamethasone oral tablets.
| Study group | Role | What they receive |
|---|---|---|
| Part A1: RRMM- KPT-8602 single agent; QoDx5/week | Experimental | Participants received KPT-8602 once daily for 5 days per week (QDx5/week) at escalated doses (completed). Receives: Drug: KPT-8602 |
| Part A2: RRMM- KPT-8602 single agent; QoDx3/week | Experimental | Participants received KPT-8602 once daily for 3 days per week (QoDx3/week). The starting dose for Part A2 will be informed by Part A1 (completed). Receives: Drug: KPT-8602 |
| Part B: RRMM- KPT-8602 with low-dose dexamethasone; QDx5/week | Experimental | Participants received KPT-8602 for 5 consecutive days (QDx5/week) in combination with low dose dexamethasone (20 milligram [mg] on Days 1, 3, 8, 10, 15, 17, 22, and 24 of each 28-day cycle) (completed). Receives: Drug: KPT-8602; Drug: Dexamethasone |
| Part C: CRC- KPT-8602 single agent | Experimental | Participants were treated with KPT-8602 at a dose and schedule that has been cleared in Part A (completed). Receives: Drug: KPT-8602 |
| Part D: mCRPC- KPT-8602 single agent | Experimental | Participants were treated with KPT-8602 at a dose and schedule that has been cleared in Part A (completed). Receives: Drug: KPT-8602 |
| Part E: mCRPC- KPT-8602 with abiraterone and corticosteroids | Experimental | Participants were treated with KPT-8602 at a dose and schedule that had been cleared in Part A in combination with abiraterone and corticosteroids. Participants continued to receive the dose and schedule of abiraterone and corticosteroids that they were receiving at the time of enrollment (completed). Receives: Drug: KPT-8602 |
| Part F: High-risk Myelodysplastic Syndrome (MDS)- KPT-8602 single agent | Experimental | Participants were treated with KPT-8602 at a dose and schedule that had been cleared in Part A. In select cases (for example, participants achieving stable disease [SD], hematological improvement [HI], partial response [PR] and tolerating treatment, etc.), the dose may be escalated 1 level based on safety and efficacy considerations (completed). Receives: Drug: KPT-8602 |
| Part F Phase 2: RR High-risk MDS- KPT-8602 single agent | Experimental | Participants will be enrolled at recommended Phase 2 doses (RP2D) of 10 mg daily on Days 1 to 5 of each week, in a dose expansion, based upon the results from the Phase 1 portion of Part F. Receives: Drug: KPT-8602 |
| Part G: Newly Diagnosed Intermediate/High-Risk MDS -KPT-8602 with ASTX727 | Experimental | Participants will receive KPT-8602 once daily at escalated doses. The starting dose for KPT-8602 is 5 mg orally once daily from Day 8 to Day 28 (Weeks 2 to 4) on a 28-day cycle in combination with ASTX727. Receives: Drug: KPT-8602; Drug: ASTX727 |
| Part H: AML Maintenance Therapy- KPT-8602 single agent | Experimental | Participants with high-risk acute myeloid leukemia (AML) prior to transplant will be enrolled to receive maintenance therapy with KPT-8602 post-allogeneic stem cell transplantation. The dose for KPT-8602 will be 10 mg (RP2D from Part F) oral, to be administered once daily from Day 1 to Day 21 (Weeks 1 to 3) on a 28-day cycle. Receives: Drug: KPT-8602 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part A1, A2, B, C, D, E, F: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)
Measured: Approximately 4 weeks
Part A1, A2, B, C, D, E, F: Overall Response Rate (ORR)
Measured: Approximately 8 years
Part A1, A2, B, C, D, E, F: Duration of Response (DOR)
Measured: Approximately 8 years
Part A1, A2, B, C, D, E, F: Progression-free Survival (PFS)
Measured: Approximately 8 years
Part A1, A2, B, C, D, E, F: Overall Survival (OS)
Measured: Approximately 8 years
Part A1, A2, B, C, D, E, F: Clinical Benefit Rate (CBR)
Measured: Approximately 8 years
Part A1, A2, B, C, D, E, F: Duration of Clinical Benefit Rate (CBR)
Measured: Approximately 8 years
Part A1, A2, B, C, D, E, F: Disease Control Rate (DCR)
Measured: Approximately 8 years
Part A1, A2, B, C, D, E, F: Duration of DCR
Measured: Approximately 8 years
Part F Phase 2: ORR
Measured: Approximately 8 years
Part G: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)
Measured: Approximately 8 years
Part H: 2- Year Progression-free Survival (PFS)
Measured: Approximately Up to 2 years
Secondary outcomes (20)
Part A1, A2, B, C, D, E, F, H: Area Under the Plasma Concentration Time Curve from Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Eltanexor
Measured: Pre-dose 2 hours post-dose Cycle 1 Day 1 and 15; Pre-dose 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Cycle 1 Day 21 and 26; 24 hours post-dose Cycle 1 Day 2, 22, and 27; 48 hours post-dose Cycle 1 Day 23 and 28 and up to approximately 8 years
Part A1, A2, B, C, D, E, F, H: Maximum Observed Plasma Concentration (Cmax) of Eltanexor
Measured: Pre-dose 2 hours post-dose Cycle 1 Day 1 and 15; Pre-dose 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Cycle 1 Day 21 and 26; 24 hours post-dose Cycle 1 Day 2, 22, and 27; 48 hours post-dose Cycle 1 Day 23 and 28 and up to approximately 8 years
Part A1, A2, B, C, D, E, F, H: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Eltanexor
Measured: Pre-dose 2 hours post-dose Cycle 1 Day 1 and 15; Pre-dose 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Cycle 1 Day 21 and 26; 24 hours post-dose Cycle 1 Day 2, 22, and 27; 48 hours post-dose Cycle 1 Day 23 and 28 and up to approximately 8 years
Part A1, A2, B, C, D, E, F, H: Apparent Terminal Half Life (t1/2) of Eltanexor
Measured: Pre-dose 2 hours post-dose Cycle 1 Day 1 and 15; Pre-dose 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Cycle 1 Day 21 and 26; 24 hours post-dose Cycle 1 Day 2, 22, and 27; 48 hours post-dose Cycle 1 Day 23 and 28 and up to approximately 8 years
Part A1, A2, B, C, D, E, F, H: Apparent Total Body Clearance Eltanexor
Measured: Pre-dose 2 hours post-dose Cycle 1 Day 1 and 15; Pre-dose 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Cycle 1 Day 21 and 26; 24 hours post-dose Cycle 1 Day 2, 22, and 27; 48 hours post-dose Cycle 1 Day 23 and 28 and up to approximately 8 years
Part A1, A2, B, C, D, E, F, H: Apparent Volume of Distribution During Terminal Phase (VZ/f) of Eltanexor
Measured: Pre-dose 2 hours post-dose Cycle 1 Day 1 and 15; Pre-dose 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Cycle 1 Day 21 and 26; 24 hours post-dose Cycle 1 Day 2, 22, and 27; 48 hours post-dose Cycle 1 Day 23 and 28 and up to approximately 8 years
Part F Phase 2: Overall Survival (OS)
Measured: Approximately 8 years
Part F Phase 2: 6-Month Overall Survival (OS)
Measured: Approximately Up to 6 Months
Part F Phase 2: Progression-free Survival (PFS)
Measured: Approximately 8 years
Part F Phase 2: Disease Control Rate (DCR)
Measured: Approximately 8 years
Part F Phase 2: Duration of Response (DOR)
Measured: Approximately 8 years
Part F Phase 2: Rate of Conversion from Red Blood Cell (RBC) Transfusion Dependence to Independence
Measured: Approximately 8 years
Part F Phase 2: Rate of Conversion from Platelet Transfusion Dependence to Independence
Measured: Approximately 8 years
Part G: Overall Response Rate (ORR)
Measured: Approximately 8 years
Part G: Duration of Response (DOR)
Measured: Approximately 8 years
Part H: Rate of Minimal Residual Disease (MRD) Conversion from Positive to Negative
Measured: Approximately 8 years
Part H: Time to Minimal Residual Disease (MRD) Negativity
Measured: Approximately 8 years
Part H: Percentage of Participants with Acute and Chronic Graft-versus-Host Disease (GVHD)
Measured: Approximately 8 years
Part H: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Measured: Approximately 8 years
Part H: Overall Survival (OS)
Measured: Approximately 8 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2016 (estimated)
- Study startJan 2016
- Primary completion31 Aug 2024
- Study completion23 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Relapsed/Refractory Multiple Myeloma (RRMM)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 277 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Karyopharm Therapeutics Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02649790
- Sponsor's protocol ID
- KCP-8602-801
- Status last verified
- Mar 2025
- First submitted
- 6 Jan 2016
- Last updated
- 19 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Lee S, Mohan S, Knupp J, Chamoun K, de Jonge A, Yang F, Baloglu E, Shah J, Kauffman MG, Shacham S, Bhatnagar B. Oral eltanexor treatment of patients with higher-risk myelodysplastic syndrome refractory to hypomethylating agents. J Hematol Oncol. 2022 Aug 3;15(1):103. doi: 10.1186/s13045-022-01319-y.
PubMed 35922861