Hematological Malignancies Clinical Trial
Official title:
A Phase I Study of the Safety, Pharmacokinetics and Pharmacodynamics of Escalating Doses of the Selective Inhibitor of Nuclear Export/SINE™ Compound KPT-330 in Patients With Advanced Hematological Malignancies
Verified date | January 2023 |
Source | Karyopharm Therapeutics Inc |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
The purpose of this research study is to find out more information relating to the highest dose of KCP-330 that can be given safely and side effects it may cause, to examine how the body affects KCP-330 concentrations in the blood (pharmacokinetics or PK), to examine the effects of KCP-330 on the body (pharmacodynamics or PDn) and to obtain information on its effectiveness in treating cancer.
Status | Completed |
Enrollment | 286 |
Est. completion date | October 13, 2015 |
Est. primary completion date | October 13, 2015 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria 1. Malignancies that are refractory to or intolerant of established therapy known to provide clinical benefit. Patients must not be candidates for anti-tumor regimes known to provide clinical benefit. 2. All patients must have evidence of progressive disease on study entry. Previously untreated patients who are not chemotherapy candidates on Arm 2 may have advanced disease (without clear progression). There is no upper limit on the number of prior treatments provided that all inclusion criteria are met, and exclusion criteria are not met. Exclusion Criteria 1. Radiation, chemotherapy, or immunotherapy or any other anticancer therapy =2 weeks prior to cycle 1 day 1 and mitomycin C and radioimmunotherapy 6 weeks prior to cycle 1 day 1. 2. Patients 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 except for patients with AML, where at least 2 months must have elapsed; 3. Known active hepatitis A, B, or C infection; or known to be positive for HCV RNA or HBsAg (HBV surface antigen); 4. Patients with active CNS malignancy. Asymptomatic small lesions are not considered active. Treated lesions may be considered inactive if they are stable for at least 3 months. Patient with malignant cells in their cerebrospinal fluid (CSF) without CNS symptom may be included. 5. Significantly diseased or obstructed gastrointestinal tract or uncontrolled vomiting or diarrhea. 6. Grade =2 peripheral neuropathy at baseline (within 14 days prior to cycle 1 day 1). 7. Macular degeneration, uncontrolled glaucoma, or markedly decreased visual acuity. 8. In the opinion of the investigator, patients who are significantly below their ideal body weight. |
Country | Name | City | State |
---|---|---|---|
Canada | Tom Baker Cancer Centre | Calgary | Alberta |
Canada | Princess Margaret Hospital | Toronto | Ontario |
Denmark | Rigshospitalet | Copenhagen | |
United States | Dana-Farber Cancer Institute | Boston | Massachusetts |
United States | Gabrail Cancer Center Research | Canton | Ohio |
United States | The Ohio State University | Columbus | Ohio |
United States | Hackensack University Medical Center | Hackensack | New Jersey |
United States | MD Anderson Cancer Center | Houston | Texas |
United States | Sarah Cannon Research Institute | Nashville | Tennessee |
United States | Weill Cornell Medical Center | New York | New York |
United States | Washington University School of Medicine | Saint Louis | Missouri |
United States | Moffitt Cancer Center | Tampa | Florida |
Lead Sponsor | Collaborator |
---|---|
Karyopharm Therapeutics Inc |
United States, Canada, Denmark,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product during the course of a study and which does not necessarily have to have a causal relationship with this treatment. An Serious adverse event (SAE) was an AE resulting in any of the following outcomes: death; life-threatening event; required or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly. TEAEs are any untoward medical incidence in a participant during administered study treatment, whether or not these events were related to study treatment. | From first dose of study drug administration to end of treatment (up to 27 months) | |
Primary | Recommended Phase 2 Dose (RP2D) of Selinexor | Recommended Phase 2 dose was determined by maximum tolerated dose (MTD). MTD was defined as the next lower dose level below the one in which > 1 of 3 participants or = 2 of 6 participants experienced dose-limiting toxicity (DLT), provided that that dose level is =25% lower than the highest dose tested. If the projected MTD was >25% lower than the highest dose tested, then an additional cohort of =3 participants were added at a dose that was intermediate between the intolerable dose and the next lower dose. | From first dose of study drug administration to end of treatment (up to 27 months) | |
Secondary | Maximum Observed Plasma Concentration (Cmax) of Selinexor | Cmax was defined as the maximum observed concentration, taken directly from the plasma concentration. | 0 (pre-dose), 0.5, 1, 2, 4, 8, 24 and 48 hours post-dose on Day 1, 8 of Cycle 1 and Days 15, 16 or 17 of Cycle 2 | |
Secondary | Time to Maximum Observed Concentration (Tmax) of Selinexor | Tmax was defined as time of first observation of Cmax, taken directly from the plasma concentration data. | 0 (pre-dose), 0.5, 1, 2, 4, 8, 24 and 48 hours post-dose on Day 1, 8 of Cycle 1 and Days 15, 16 or 17 of Cycle 2 | |
Secondary | Average Concentration From Time 0 to 24 Hours (Cavg0-24h) of Selinexor | Cavg0-24h was defined as average concentration from time 0 to 24 hours. | 0 (pre-dose), 0.5, 1, 2, 4, 8, 24 and 48 hours post-dose on Day 1, 8 of Cycle 1 and Days 15, 16 or 17 of Cycle 2 | |
Secondary | Area Under the Concentration-Time Curve From Time 0 to t (AUC0-t) of Selinexor | AUC0-t was defined as area under the concentration-time curve from time zero to the last non-zero concentration. | 0 (pre-dose), 0.5, 1, 2, 4, 8, 24 and 48 hours post-dose on Day 1, 8 of Cycle 1 and Days 15, 16 or 17 of Cycle 2 | |
Secondary | Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Selinexor | AUC0-inf was defined as the area under the concentration-time curve from time zero to infinity (extrapolated). | 0 (pre-dose), 0.5, 1, 2, 4, 8, 24 and 48 hours post-dose on Day 1, 8 of Cycle 1 and Days 15, 16 or 17 of Cycle 2 | |
Secondary | Apparent Volume of Distribution Uncorrected for Fraction Absorbed (Vd/F) of Selinexor | Apparent volume of distribution was calculated as Dose/ (kel *AUC0-inf), uncorrected for fraction absorbed, reported normalized by participant body weight (kilogram [kg]). | 0 (pre-dose), 0.5, 1, 2, 4, 8, 24 and 48 hours post-dose on Day 1, 8 of Cycle 1 and Days 15, 16 or 17 of Cycle 2 | |
Secondary | Apparent Total Body Clearance, Uncorrected for Fraction Absorbed (Cl/F) of Selinexor | Cl/F was calculated as Dose/AUC0-inf, uncorrected for fraction absorbed, reported normalized by participant body weight (kg). | 0 (pre-dose), 0.5, 1, 2, 4, 8, 24 and 48 hours post-dose on Day 1, 8 of Cycle 1 and Days 15, 16 or 17 of Cycle 2 | |
Secondary | Terminal Half-Life (t½) of Selinexor | t½ was, calculated as ln(2)/kel, where kel is elimination rate constant, calculated using linear regression on the terminal portion of the log-linear concentration versus time curve. | 0 (pre-dose), 0.5, 1, 2, 4, 8, 24 and 48 hours post-dose on Day 1, 8 of Cycle 1 and Days 15, 16 or 17 of Cycle 2 | |
Secondary | Number of Participants With Overall Response of Selinexor | Objective response for each malignancy was defined using the disease response criteria by malignancy; For NHL (including DLBCL, PTCL, and CTCL), objective response included complete response (CR) and partial response (PR). For MM, objective response included stringent complete response (sCR), CR, very good partial response (VGPR), and PR. For WM, objective response included CR, VGPR, and PR. For CLL, ALL, and AML, objective response included complete remission and Partial remission. For CML, objective response includes complete cytogenic response, and complete hematologic response (CHR). | From first dose of study drug administration to end of treatment (up to 27 months) | |
Secondary | Duration of Response | Duration of response was defined as the time from the first occurrence of objective response to first documented evidence of disease recurrence or progression. Participants without evidence of progression were censored at time of last evaluable disease assessment. Objective response was defined as any response of partial response/remission or better for all malignancies; for AML, a response of morphologic leukemia-free state is also included for ORR. Duration of response was calculated by Kaplan-Meier method. | From first dose of study drug administration to end of treatment (up to 27 months) | |
Secondary | Progression-free Survival | Progression-free survival (PFS) was calculated from the date of first dose of study drug to first documented evidence of disease recurrence or progression or death due to any cause. Participants who were last known to be alive and without evidence of progression were censored at time of last evaluable disease assessment. If date of progression or death occurred after more than 1 missed disease assessment interval, participants were censored at the time of last evaluable disease assessment prior to the missed assessment. | Cycle 1 Day 1 to End of Treatment (up to 27 months) | |
Secondary | Duration of at Least Stable Disease | Duration of at least stable disease was defined as the time from the date of first dose of study drug to first documented evidence of disease recurrence or progression. Participants without evidence of progression were censored at time of last evaluable disease assessment. | Cycle 1 Day 1 to End of Treatment (up to 27 months) | |
Secondary | Overall Survival | Overall Survival was calculated from the date of first dose of study drug to date of death due to any cause. Participants who were last known to be alive were censored at time of last contact. Overall survival was calculated by Kaplan-Meier method. | Cycle 1 Day 1 to End of Treatment (up to 27 months) |
Status | Clinical Trial | Phase | |
---|---|---|---|
Terminated |
NCT03248479 -
Magrolimab Monotherapy or Magrolimab in Combination With Azacitidine in Participants With Hematological Malignancies
|
Phase 1 | |
Recruiting |
NCT05454241 -
CD7 CAR-T for Patients With r/r CD7+ Hematologic Malignancies
|
Phase 2 | |
Recruiting |
NCT06041815 -
Correlation Between Gut Microbiota and Clinical Response to CAR-T Treatment for Hematological Malignancies
|
||
Active, not recruiting |
NCT05005442 -
A Study of Pembrolizumab/Vibostolimab (MK-7684A) in Relapsed/Refractory Hematological Malignancies (MK-7684A-004, KEYVIBE-004)
|
Phase 2 | |
Recruiting |
NCT02300571 -
Observational Study of the Combination of Post-transplant High Dose Cyclophosphamide, Tacrolimus and Mycophenolate Mofetil for the Prevention of Acute Graft-versus-Host Disease in Patients Eligible to Allogeneic Hematopoietic Stem Cell Transplant
|
N/A | |
Active, not recruiting |
NCT01428973 -
Minitransplants With HLA-matched Donors : Comparison Between 2 GVHD Prophylaxis Regimens
|
Phase 2 | |
Completed |
NCT01162096 -
Reduced Intensity Haploidentical Transplant for Hematological Malignancies
|
Phase 1/Phase 2 | |
Completed |
NCT00379587 -
Rituximab for Prevention of Chronic GVHD
|
Phase 1/Phase 2 | |
Terminated |
NCT00506948 -
Thymoglobulin, Sirolimus and Mycophenolate Mofetil for Prevention of Acute Graft-Versus-Host Disease (GVHD)
|
Phase 2 | |
Active, not recruiting |
NCT04557098 -
A Study of Teclistamab in Participants With Relapsed or Refractory Multiple Myeloma
|
Phase 2 | |
Recruiting |
NCT04283097 -
Safety, Tolerability and Pharmacokinetics Study of KPG-818 in Hematological Malignancies Subjects
|
Phase 1 | |
Completed |
NCT03067155 -
CMV Specific T Cell Therapy After Allogeneic Stem Cell Transplantation.
|
Phase 2 | |
Completed |
NCT01725555 -
A Study to Assess the Effect of Food on the Bioavailability of the IGF-1R Inhibitor AXL1717 in Patients With Advanced Malignant Tumors
|
Phase 1 | |
Completed |
NCT00438178 -
Safety and Efficacy of Obatoclax Mesylate (GX15-070MS) for the Treatment of Hematological Malignancies
|
Phase 1 | |
Completed |
NCT03711604 -
Compassionate Use Study of Tenalisib (RP6530)
|
Phase 1/Phase 2 | |
Withdrawn |
NCT01168882 -
Safety and Tolerability of RGB-286638 in Patients With Selected, Relapsed or Refractory Hematological Malignancies
|
Phase 1 | |
Completed |
NCT01246206 -
Tacrolimus and Thymoglobulin, as GvHD Prophylaxis in Patients Undergoing Related Donor HCT
|
Phase 2 | |
Completed |
NCT01172132 -
The Use of Intensive Care in Critically Ill Cancer Haematological Patients: "TRIAL-OH"
|
N/A | |
Completed |
NCT00506402 -
A Phase 1 Study of MKC-1 in Patients With Refractory Hematologic Malignancies
|
Phase 1 | |
Active, not recruiting |
NCT00163644 -
RCT to Investigate Whether an Exercise Programme Improves the Physical Performance and QOL After BMT
|
N/A |