A Phase 2 interventional study of Selinexor and Fludarabine in Acute Myeloid Leukemia (AML), sponsored by St. Jude Children's Research Hospital. Terminated at 7 sites in United States. Open to participants aged Up to 24 Years. Per ClinicalTrials.gov, last updated 2020-05-22.
Sponsored by St. Jude Children's Research Hospital · Phase 2, Interventional, and Treatment
This study will be done in two parts: Phase I (NCT02212561) has been completed and published. The goal of the Phase I portion of this study was to find the highest tolerable dose of selinexor (KPT-330) that can be given to patients with leukemia or myelodysplastic syndrome (MDS), when it is combined with fludarabine and cytarabine.
The Phase II portion of the protocol is reflected in this registration.
The goal of the Phase II portion of this protocol is to give the highest dose of selinexor (KPT-330) in combination with fludarabine/cytarabine that was found in Phase I to be safe for children with acute myeloid leukemia (AML). The investigators will examine the effect of this combination treatment.
After the recommended Phase II dose was determined, additional patients began enrolling to receive selinexor at the recommended dose level for further evaluation of tolerability and response.
PRIMARY OBJECTIVE:
5,441 studies on the registry are indexed under Leukemia; 636 are open to participants now.
This study's enrollment of 37 is close to the median of 38 across 4,247 interventional studies indexed under Leukemia.
Browse Leukemia studies →St. Jude Children's Research Hospital is the lead sponsor of 434 studies on the registry; 99 are open to participants now.
Of its 60 completed or terminated interventional studies of FDA-regulated products, 35 (58%) have results posted.
Counted across the registry records on this site, refreshed daily.
Participants must have a diagnosis of AML and must have disease that has relapsed or is refractory to chemotherapy, or that has relapsed after hematopoietic stem cell transplantation (HSCT)
Adequate organ function defined as the following:
Exclusion Criteria:
Unstable cardiovascular function:
Interventions: Selinexor, Fludarabine, and Cytarabine. Methotrexate/hydrocortisone/cytarabine (intrathecal triples) will be given prior to cycle 1.
Drug: Selinexor · Drug: Fludarabine · Drug: Cytarabine · Drug: methotrexate/hydrocortisone/cytarabine
Given orally on days 1,3,8,10,22 and 24 of each cycle
Also known as: KPT-330
Will be given intravenously (IV) over 30 minutes daily on days 16 through 20. Fludarabine may be given prior to day 16 if it is determined to be in the participant's best interest based on disease progression. Chemotherapy may be delayed by 1-3 days if clinically indicated.
Also known as: Fludara®, Fludarabine phosphate, 2-fluoro-ara-AMP
Will be given IV over 4 hours daily on days 16 through 20. Cytarabine may be given prior to day 16 if it is determined to be in the participant's best interest based on disease progression. Chemotherapy may be delayed by 1-3 days if clinically indicated.
Also known as: Cytosine arabinoside, Ara-C, Cytosar®
Intrathecal (IT) triples will be given prior to cycle 1: IT cytarabine, IT methotrexate, and IT methotrexate/hydrocortisone/cytarabine (MHA) are acceptable. Patients without evidence of central nervous system (CNS) leukemia will receive no further IT therapy during cycle 1. Patients with CNS disease will receive weekly ITMHA until the cerebrospinal fluid becomes free of leukemia (minimum of 4 doses).
Also known as: ITMHA, Intrathecal triples
The Overall Response (OR) Rate (Complete Response + Incomplete Count Recovery + Partial Response)
Complete response or complete response with incomplete count recovery or partial response, of selinexor in combination with fludarabine and cytarabine for patients with relapsed or refractory AML in the phase II portion of the study
Time frame: Between days 28 and 35 of cycle 1 (cycle length is 42-56 days)
Complete Response
Complete response, of selinexor in combination with fludarabine and cytarabine for patients with relapsed or refractory AML in the phase II portion of the study
Time frame: Between days 28 and 35 of cycle 1 (cycle length is 42-56 days)
Complete Response or Complete Response With Incomplete Count Recovery
Complete response or complete response with incomplete count recovery, of selinexor in combination with fludarabine and cytarabine for patients with relapsed or refractory AML in the phase II portion of the study
Time frame: Between days 28 and 35 of cycle 1 (cycle length is 42-56 days)
Participants must have a diagnosis of AML and must have disease that has relapsed or is refractory to chemotherapy, or that has relapsed after hematopoietic stem cell transplantation (HSCT).
| Milestone | Interventions: Selinexor, Fludarabine, and Cytarabine |
|---|---|
| Started | 37 |
| Completed | 22 |
| Not completed | 15 |
| Withdrew: Adverse event | 1 |
| Withdrew: Lack of efficacy | 14 |
Complete response or complete response with incomplete count recovery or partial response, of selinexor in combination with fludarabine and cytarabine for patients with relapsed or refractory AML in the phase II portion of the study
| percentage of participants | Interventions: Selinexor, Fludarabine, and Cytarabine |
|---|---|
| The Overall Response (OR) Rate (Complete Response + Incomplete Count Recovery + Partial Response) | 53.6 (33.9 to 72.5) |
Complete response, of selinexor in combination with fludarabine and cytarabine for patients with relapsed or refractory AML in the phase II portion of the study
| percentage of participants | Interventions: Selinexor, Fludarabine, and Cytarabine |
|---|---|
| Complete Response | 46.4 (27.5 to 66.1) |
Complete response or complete response with incomplete count recovery, of selinexor in combination with fludarabine and cytarabine for patients with relapsed or refractory AML in the phase II portion of the study
| percentage of participants | Interventions: Selinexor, Fludarabine, and Cytarabine |
|---|---|
| Complete Response or Complete Response With Incomplete Count Recovery | 50.0 (30.6 to 69.4) |
Collected over Adverse Events (AEs) were collected for 30 days after completion of treatment plan or until other anti-leukemia therapy was initiated. If discontinuation from study was due to an AE considered related to study treatment, a follow-up visit was conducted no later than 30 days after the last dose of protocol therapy with recommended safety assessments at least every 30 days, until all toxicities resolved, returned to baseline or became clinically satisfactory, stable, or considered irreversible.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Interventions: Selinexor, Fludarabine, and Cytarabine | 22/37 (59.5%) | 1/37 (2.7%) | 36/37 (97.3%) |
| Event | Interventions: Selinexor, Fludarabine, and Cytarabine |
|---|---|
| Pleural effusionRespiratory, thoracic and mediastinal disorders | 1/37 |
| Pericardial effusionCardiac disorders | 1/37 |
| Event | Interventions: Selinexor, Fludarabine, and Cytarabine |
|---|---|
| Platelet count decreasedInvestigations | 33/37 |
| Neutrophil count decreasedInvestigations | 31/37 |
| AnemiaBlood and lymphatic system disorders | 30/37 |
| White blood cell decreasedInvestigations | 29/37 |
| Lymphocyte count decreasedInvestigations | 23/37 |
| Febrile neutropeniaBlood and lymphatic system disorders | 18/37 |
| HyponatremiaMetabolism and nutrition disorders | 18/37 |
| HyperglycemiaMetabolism and nutrition disorders | 11/37 |
| HypokalemiaMetabolism and nutrition disorders | 11/37 |
| Lung infectionInfections and infestations | 7/37 |
Participants must have a diagnosis of AML and must have disease that has relapsed or is refractory to chemotherapy, or that has relapsed after hematopoietic stem cell transplantation (HSCT)
| Age, Continuous(years) | Interventions: Selinexor, Fludarabine, and Cytarabine |
|---|---|
| Mean | 9.65 ± 6.25 |
| Age, Continuous(years) | Interventions: Selinexor, Fludarabine, and Cytarabine |
|---|---|
| Median | 8.04 ± 6.25 |
| Sex: Female, Male(Participants) | Interventions: Selinexor, Fludarabine, and Cytarabine |
|---|---|
| Female | 15 |
| Male | 22 |
| Ethnicity (NIH/OMB)(Participants) | Interventions: Selinexor, Fludarabine, and Cytarabine |
|---|---|
| Hispanic or Latino | 12 |
| Not Hispanic or Latino | 24 |
| Unknown or Not Reported | 1 |
| Race (NIH/OMB)(Participants) | Interventions: Selinexor, Fludarabine, and Cytarabine |
|---|---|
| American Indian or Alaska Native | 1 |
| Asian | 5 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 3 |
| White | 25 |
| More than one race | 1 |
| Unknown or Not Reported | 2 |
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