Selinexor in Combination With Fludarabine and Cytarabine in Patients With Refractory or Relapsed Acute Myeloid Leukemia

NCT03071276 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: SELHEM-2NCI-2014-01704
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Acute Myeloid Leukemia (AML)

Outcome Measures

Primary Outcomes (3)

• 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

  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

  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

  Between days 28 and 35 of cycle 1 (cycle length is 42-56 days)

Study Arms (1)

Treatment Arm

EXPERIMENTAL

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

Interventions

Selinexor DRUG

Given orally on days 1,3,8,10,22 and 24 of each cycle

Also known as: KPT-330

Treatment Arm

Fludarabine DRUG

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

Treatment Arm

Cytarabine DRUG

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®

Treatment Arm

methotrexate/hydrocortisone/cytarabine DRUG

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

Treatment Arm

Eligibility Criteria

• Age: Up to 24 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)
• Refractory disease is defined as persistent disease after at least two courses of induction chemotherapy.
• Patients are eligible at first or subsequent relapse or any relapse that is refractory to salvage chemotherapy.
• Patients must have ≥ 5% leukemic blasts in the bone marrow and/or increasing levels of MRD in the bone marrow as assessed by flow cytometry. If an adequate bone marrow sample cannot be obtained, patients may be enrolled if there is unequivocal evidence of leukemia in the peripheral blood.
• Adequate organ function defined as the following:
• Direct bilirubin ≤ 1.5 x institutional upper limit of normal (IULN)
• AST (SGOT)/ALT (SGPT) \< 3 x IULN
• Creatinine within normal institutional limits for age
• Prothrombin time (PT) and partial thromboplastin (PTT) ≤ 1.5 x IULN.
• Age criteria: Patients treated at collaborating sites and current St. Jude patients who are on therapy or within 3 years of completion of therapy must be ≤ 24 years old. All other St. Jude patients must be ≤ 21 years old.
• Patients must be able to swallow tablets.
• Performance status: Lansky ≥ 50 for patients who are ≤ 16 years old and Karnofsky ≥ 50% for patients who are \> 16 years old.
• Patients must have fully recovered from the acute effects of all prior therapy.
• For patients who have received prior HSCT, there can be no evidence of GVHD and greater than 60 days must have elapsed since the HSCT.

You may not qualify if:

• History of cerebellar toxicity or cerebellar neurological findings on exam.
• Must not be pregnant or breastfeeding. Female patients of child-bearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening, and male patients must use an effective barrier method of contraception if sexually active with a female of child-bearing potential. Acceptable methods of contraception are condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal. For both male and female patients, effective methods of contraception must be used throughout the study and for three months following the last dose.
• Patients with Down syndrome, acute promyelocytic leukemia, juvenile myelomonocytic leukemia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome, or other bone marrow failure syndromes are not eligible.
• Use of investigational agents, with the exception of gemtuzumab ozogamicin, within 30 days.
• Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, study participation, follow up, or interpretation of study research.
• Unstable cardiovascular function:
• symptomatic ischemia
• congestive heart failure NYHA Class \> 3
• myocardial infarction (MI) within 3 months
• Uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose. Infections controlled on concurrent anti-microbial agents are acceptable, and anti-microbial prophylaxis per institutional guidelines are acceptable.
• Known human immunodeficiency virus (HIV) infection (pre-study testing not required).
• Patients with malabsorption syndrome, or any other disease significantly affecting gastrointestinal function.
• Prior treatment with selinexor.

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead
• Karyopharm Therapeutics Inc: collaborator

Study Sites (7)

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

Lucile Packard Children's Hospital Stanford University

Palo Alto, California, 94304, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Children's Hospital of Michigan

Detroit, Michigan, 48201, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

Related Publications (1)

• Alexander TB, Lacayo NJ, Choi JK, Ribeiro RC, Pui CH, Rubnitz JE. Phase I Study of Selinexor, a Selective Inhibitor of Nuclear Export, in Combination With Fludarabine and Cytarabine, in Pediatric Relapsed or Refractory Acute Leukemia. J Clin Oncol. 2016 Dec;34(34):4094-4101. doi: 10.1200/JCO.2016.67.5066. Epub 2016 Oct 31.

  PMID: 27507877 RESULT

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

selinexor; fludarabine; fludarabine phosphate; Cytarabine; Methotrexate

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Jeffrey E. Rubnitz, MD, PhD
• Organization: St. Jude Children's Research Hospital

jeffrey.rubnitz@stjude.org

901-595-2388

Study Officials

• Jeffrey E. Rubnitz, MD,PhD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2017
• First Posted: March 6, 2017
• Study Start: January 14, 2016
• Primary Completion: April 30, 2019
• Study Completion: April 30, 2019
• Last Updated: May 22, 2020
• Results First Posted: April 24, 2020

Record last verified: 2020-05

Locations

US (7)