Multiple Myeloma
Conditions
Keywords
autologous hematopoietic cell transplantation (HCT), high-dose melphalan, selinexor
Brief summary
Phase I: The primary purpose of this study phase is to determine the best dose also referred to as the maximum tolerated dose (MTD) of Selinexor when used in combination with high-dose melphalan as a conditioning regimen for hematopoietic cell transplant. Phase II: The primary purpose of this study phase is to assess the complete response (CR) conversion rate.
Interventions
DRUGSelinexor
Selinexor will be given orally 2 to 3 hours prior to high dose-melphalan IV infusion. Phase I: Dose escalation beginning with 40 mg to determine the recommended Phase II dose (RPh2D). Phase II: Treatment at RPh2D.
DRUGMelphalan
Melphalan 100 mg/m\^2 IV over 30-45 minutes.
DRUGDexamethasone
Dexamethasone 20 mg PO (or IV) daily (on days -3, -2 and -1).
PROCEDUREAutologous Hematopoietic Cell Transplantation (HCT)
Participant's own stem cells are collected from their blood, frozen, then given back to them after chemotherapy.
DRUGFosaprepitant
Fosaprepitant at 150 mg IV on days -3 and -2.
Sponsors
Karyopharm Therapeutics Inc
H. Lee Moffitt Cancer Center and Research Institute
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years of age or older with histologically confirmed multiple myeloma * Achieving partial response (PR) or very good partial response (VGPR) with systemic chemotherapy * Received less than 4 lines of anti-myeloma therapy. * Karnofsky performance status of \>= 70% * Adequate pulmonary, cardiac, hepatic and renal function as outlined in the protocol * Signed informed consent form in accordance with institutional policies prior to the initiation of high-dose therapy
Exclusion criteria
* Non-secretory multiple myeloma * Have achieved complete response (CR) prior to autologous hematopoietic cell transplantation (HCT) * Central nervous system (CNS) involvement * Uncontrolled bacterial, viral or fungal infections * Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. * Prior malignancies within the last 5 years except resected basal cell carcinoma or treated cervical carcinoma in situ. * Females who are pregnant or breastfeeding * Have received other investigational drugs within 14 days prior to screening * Prior autologous or allogeneic HCT * Prior organ transplant or autoimmune disease requiring immunosuppressive therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase I: Recommended Phase II Dose (RPh2D) | Up to 3 months | RPh2D/Maximum Tolerated Dose (MTD) of Selinexor when used in combination with high-dose melphalan as a conditioning regimen for hematopoietic cell transplant. MTD: the highest dose level at which 1 or less of 6 participants experience a dose limiting toxicity (DLT). |
| Complete Response (CR) | 3 months post HCT | Complete response (CR) conversion rate. CR: Negative immunofixation of serum and urine, disappearance of any soft tissue plasmacytomas, and ≤ 5% plasma cells in bone marrow. tissue plasmacytomas, and ≤ 5% plasma cells in bone marrow. Complete Response conversion rate. CR: Negative immunofixation of serum and urine, disappearance of any soft tissue plasmacytomas, and ≤ 5% plasma cells in bone marrow. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | at 24 months | Rate of participants' survival at time of evaluation. |
| Rate of Minimal Residual Disease (MRD) | 3 months post HCT | Rate of participants who did not have Minimal Residual Disease (MRD) as assessed by flow cytometry. |
| Phase 1 and Phase 2 Percentage of Participants Treated at Dose Level 3/RP2D With Progression Free Survival (PFS) | at 24 months | Progression Free Survival defined as the time from start of treatment to the time of progression or death. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Phase 1 Level 1: Selinexor Plus HDM HCT 40 mg Selinexor given orally 2 to 3 hours prior to high dose-melphalan IV infusion Melphalan: Melphalan 100 mg/m\^2 IV over 30-45 minutes. Dexamethasone: Dexamethasone 20 mg PO (or IV) daily (on days -3, -2 and -1). Autologous Hematopoietic Cell Transplantation (HCT): Participant's own stem cells are collected from their blood, frozen, then given back to them after chemotherapy.
Fosaprepitant: Fosaprepitant at 150 mg IV on days -3 and -2. | 3 |
| Phase 1 Level 2: Selinexor Plus HDM HCT 60 mg Selinexor given orally 2 to 3 hours prior to high dose-melphalan IV infusion Melphalan: Melphalan 100 mg/m\^2 IV over 30-45 minutes. Dexamethasone: Dexamethasone 20 mg PO (or IV) daily (on days -3, -2 and -1). Autologous Hematopoietic Cell Transplantation (HCT): Participant's own stem cells are collected from their blood, frozen, then given back to them after chemotherapy.
Fosaprepitant: Fosaprepitant at 150 mg IV on days -3 and -2. | 3 |
| Phase 1 Level 3: Selinexor Plus HDM HCT 80 mg Selinexor given orally 2 to 3 hours prior to high dose-melphalan IV infusion Melphalan: Melphalan 100 mg/m\^2 IV over 30-45 minutes. Dexamethasone: Dexamethasone 20 mg PO (or IV) daily (on days -3, -2 and -1). Autologous Hematopoietic Cell Transplantation (HCT): Participant's own stem cells are collected from their blood, frozen, then given back to them after chemotherapy.
Fosaprepitant: Fosaprepitant at 150 mg IV on days -3 and -2. | 6 |
| Phase 2: Selinexor Plus HDM HCT 80 mg Selinexor given orally 2 to 3 hours prior to high dose-melphalan IV infusion Melphalan: Melphalan 100 mg/m\^2 IV over 30-45 minutes. Dexamethasone: Dexamethasone 20 mg PO (or IV) daily (on days -3, -2 and -1). Autologous Hematopoietic Cell Transplantation (HCT): Participant's own stem cells are collected from their blood, frozen, then given back to them after chemotherapy.
Fosaprepitant: Fosaprepitant at 150 mg IV on days -3 and -2. | 10 |
| Total | 22 |
Baseline characteristics
| Characteristic | Phase 1 Level 1: Selinexor Plus HDM HCT | Phase 1 Level 2: Selinexor Plus HDM HCT | Phase 1 Level 3: Selinexor Plus HDM HCT | Phase 2: Selinexor Plus HDM HCT | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 2 Participants | 5 Participants | 9 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 3 Participants | 6 Participants | 10 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 2 Participants | 5 Participants | 7 Participants | 17 Participants |
| Region of Enrollment United States | 3 participants | 3 participants | 6 participants | 10 participants | 22 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 3 Participants | 4 Participants | 9 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 3 Participants | 6 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 3 | 0 / 3 | 2 / 6 | 0 / 10 |
| other Total, other adverse events | 3 / 3 | 2 / 3 | 6 / 6 | 10 / 10 |
| serious Total, serious adverse events | 3 / 3 | 2 / 3 | 3 / 6 | 5 / 10 |
Outcome results
Primary
Complete Response (CR)
Complete response (CR) conversion rate. CR: Negative immunofixation of serum and urine, disappearance of any soft tissue plasmacytomas, and ≤ 5% plasma cells in bone marrow. tissue plasmacytomas, and ≤ 5% plasma cells in bone marrow. Complete Response conversion rate. CR: Negative immunofixation of serum and urine, disappearance of any soft tissue plasmacytomas, and ≤ 5% plasma cells in bone marrow.
Time frame: 3 months post HCT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selinexor Plus HDM HCT | Complete Response (CR) | 0 percentage of participants with CR |
| Phase 1 Level 2: Selinexor Plus HDM HCT | Complete Response (CR) | 33.3 percentage of participants with CR |
| Phase 1 Level 3: Selinexor Plus HDM HCT | Complete Response (CR) | 16.6 percentage of participants with CR |
| Phase 2: Selinexor Plus HDM HCT | Complete Response (CR) | 10 percentage of participants with CR |
Primary
Phase I: Recommended Phase II Dose (RPh2D)
RPh2D/Maximum Tolerated Dose (MTD) of Selinexor when used in combination with high-dose melphalan as a conditioning regimen for hematopoietic cell transplant. MTD: the highest dose level at which 1 or less of 6 participants experience a dose limiting toxicity (DLT).
Time frame: Up to 3 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selinexor Plus HDM HCT | Phase I: Recommended Phase II Dose (RPh2D) | 80 mg |
Other Pre-specified
Overall Survival (OS)
Rate of participants' survival at time of evaluation.
Time frame: at 24 months
Population: All evaluable participants treated at dose level 3/RP2D.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selinexor Plus HDM HCT | Overall Survival (OS) | 95.2 percent |
Other Pre-specified
Phase 1 and Phase 2 Percentage of Participants Treated at Dose Level 3/RP2D With Progression Free Survival (PFS)
Progression Free Survival defined as the time from start of treatment to the time of progression or death.
Time frame: at 24 months
Population: All evaluable participants treated at dose level 3/RP2D.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selinexor Plus HDM HCT | Phase 1 and Phase 2 Percentage of Participants Treated at Dose Level 3/RP2D With Progression Free Survival (PFS) | 66.7 percent of participants |
Other Pre-specified
Rate of Minimal Residual Disease (MRD)
Rate of participants who did not have Minimal Residual Disease (MRD) as assessed by flow cytometry.
Time frame: 3 months post HCT
Population: Evaluable participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selinexor Plus HDM HCT | Rate of Minimal Residual Disease (MRD) | 33.3 percentage of participants |
| Phase 1 Level 2: Selinexor Plus HDM HCT | Rate of Minimal Residual Disease (MRD) | 100 percentage of participants |
| Phase 1 Level 3: Selinexor Plus HDM HCT | Rate of Minimal Residual Disease (MRD) | 16.7 percentage of participants |
| Phase 2: Selinexor Plus HDM HCT | Rate of Minimal Residual Disease (MRD) | 33.3 percentage of participants |