NCT02780609 · REGISTRY CONDITION SEARCH

Selinexor Plus High-Dose Melphalan (HDM) Before Autologous Hematopoietic Cell Transplantation for Multiple Myeloma

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1, PHASE2
Status at capture: COMPLETED
Registry last update: 2022-11-04

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Phase I: Recommended Phase II Dose (RPh2D)

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outcome · POSTED

Complete Response (CR)

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outcome · POSTED

Phase 1 and Phase 2 Percentage of Participants Treated at Dose Level 3/RP2D With Progression Free Survival (PFS)

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

Rate of Minimal Residual Disease (MRD)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: 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
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
The conditioning regimen begins 3 days prior to autologous transplant. Day 0 is the day of the autologous hematopoietic cell transplant. Melphalan will be given intravenously (IV) on Day -3 and Day -2; Dexamethasone will be given through via IV on Day -3, Day -2 and Day -1; fosaprepitant at 150 IV on days -3 and -2 will be given to patients an an antiemetic.Selinexor will be taken by mouth (PO) daily on the same day participants receive chemotherapy with melphalan.
intervention Names
Drug: Selinexor
Drug: Melphalan
Drug: Dexamethasone
Procedure: Autologous Hematopoietic Cell Transplantation (HCT)
Drug: Fosaprepitant
label
Selinexor Plus HDM HCT
type
EXPERIMENTAL

interventions

arm Group Labels
Selinexor Plus HDM HCT
description
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.
name
Selinexor
other Names
KPT-330
type
DRUG
arm Group Labels
Selinexor Plus HDM HCT
description
Melphalan 100 mg/m\^2 IV over 30-45 minutes.
name
Melphalan
other Names
Alkeran
type
DRUG
arm Group Labels
Selinexor Plus HDM HCT
description
Dexamethasone 20 mg PO (or IV) daily (on days -3, -2 and -1).
name
Dexamethasone
other Names
Decadron
type
DRUG
arm Group Labels
Selinexor Plus HDM HCT
description
Participant's own stem cells are collected from their blood, frozen, then given back to them after chemotherapy.
name
Autologous Hematopoietic Cell Transplantation (HCT)
type
PROCEDURE
arm Group Labels
Selinexor Plus HDM HCT
description
Fosaprepitant at 150 mg IV on days -3 and -2.
name
Fosaprepitant
other Names
antiemetic agent
Standare of Care
type
DRUG

Study design

allocation

intervention Model

SEQUENTIAL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 22
type: ACTUAL

Registered outcome plans (not posted results)

other Outcomes

description
Progression Free Survival defined as the time from start of treatment to the time of progression or death.
measure
Phase 1 and Phase 2 Percentage of Participants Treated at Dose Level 3/RP2D With Progression Free Survival (PFS)
time Frame
at 24 months
description
Rate of participants' survival at time of evaluation.
measure
Overall Survival (OS)
time Frame
at 24 months
description
Rate of participants who did not have Minimal Residual Disease (MRD) as assessed by flow cytometry.
measure
Rate of Minimal Residual Disease (MRD)
time Frame
3 months post HCT

primary Outcomes

description
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).
measure
Phase I: Recommended Phase II Dose (RPh2D)
time Frame
Up to 3 months
description
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.
measure
Complete Response (CR)
time Frame
3 months post HCT

Full study description

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.

Source references

references

citation
Turner JG, Cui Y, Bauer AA, Dawson JL, Gomez JA, Kim J, Cubitt CL, Nishihori T, Dalton WS, Sullivan DM. Melphalan and Exportin 1 Inhibitors Exert Synergistic Antitumor Effects in Preclinical Models of Human Multiple Myeloma. Cancer Res. 2020 Dec 1;80(23):5344-5354. doi: 10.1158/0008-5472.CAN-19-0677. Epub 2020 Oct 6.
pmid
33023948
type
DERIVED