Clinical Trials /

KPT-330 Plus RICE for Relapsed/Refractory Aggressive B-Cell Lymphoma

NCT02471911

Description:

This study evaluates the addition of selinexor (KPT-330) to RICE chemotherapy in the treatment of relapsed and refractory aggressive B-Cell Lymphoma, with the goal of improved response rates (as compared to RICE chemotherapy alone).

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Diffuse Large B-Cell Lymphoma Activated B-Cell Type
  • Double-Hit Lymphoma
  • Germinal Center B-Cell-Like Diffuse Large B-Cell Lymphoma
  • Grade 3b Follicular Lymphoma
  • Primary Mediastinal B-Cell Lymphoma
  • Transformed Lymphoma
  • Triple-Hit Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: KPT-330 Plus RICE for Relapsed/Refractory Aggressive B-Cell Lymphoma
  • Official Title: A Phase I Investigator-Initiated Study of Selinexor (KPT-330) Plus RICE in Patients With Relapsed or Refractory Aggressive B-cell Lymphomas

Clinical Trial IDs

  • ORG STUDY ID: 1502015891
  • NCT ID: NCT02471911

Conditions

  • Diffuse Large B-Cell Lymphoma

Interventions

DrugSynonymsArms
KPT-330SelinexorAll subjects
RituximabRituxanAll subjects
EtoposideAll subjects
CarboplatinAll subjects
IfosfamideAll subjects
DexamethasoneAll subjects

Purpose

This study evaluates the addition of selinexor (KPT-330) to RICE chemotherapy in the treatment of relapsed and refractory aggressive B-Cell Lymphoma, with the goal of improved response rates (as compared to RICE chemotherapy alone).

Detailed Description

      Although aggressive B-cell lymphomas are potentially curable with front-line chemotherapy, at
      least one-third of patients experience progression or relapse. Second-line regimens such as
      rituximab, ifosfamide, carboplatin, and etoposide (RICE) are administered with the goal of
      cytoreduction prior to autologous stem cell transplantation (ASCT) in eligible patients.
      However, half of patients who receive salvage treatment and ASCT are still not cured.

      Selinexor is a Selective Inhibitor of Nuclear Export / SINE compound, which is a new class of
      molecule. SINE compounds have been shown to induce apoptotic cell death in pre-clinical
      models of AML, CLL, T-ALL, and Ph+ ALL as well as B and T-cell non-Hodgkin lymphomas.
      Preliminarily, selinexor has demonstrated promising single-agent clinical activity in
      patients with previously treated NHL including DLBCL, warranting further investigation. Based
      on promising preclinical and clinical data, selinexor is currently under evaluation in
      combination with chemotherapy for solid tumors.

      The investigators hypothesize that the combination of selinexor plus RICE will be
      well-tolerated and clinically active in participants with previously treated aggressive
      B-cell lymphomas and propose a phase I trial to evaluate this combination. Moreover,
      Investigators will evaluate primary patient samples before and after selinexor to investigate
      the mechanisms of action of selinexor, including the mechanisms by which selinexor sensitizes
      cells to chemotherapy, and evaluate other novel drug combinations in aggressive B-cell
      lymphomas.
    

Trial Arms

NameTypeDescriptionInterventions
All subjectsExperimentalAll subjects will receive KPT-330 (selinexor) on days -5 and -3 starting one week before RICE chemotherapy is started. Once chemotherapy starts, selinexor will be given on days 1, 3, and 5 of each chemotherapy cycle. RICE chemotherapy will consist of Rituximab, ifosfamide, carboplatin, etoposide, and dexamethasone.
  • KPT-330
  • Rituximab
  • Etoposide
  • Carboplatin
  • Ifosfamide
  • Dexamethasone

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have histologically confirmed aggressive B-cell non-Hodgkin lymphomas:

               -  DLBCL including ABC, GCB or PMBCL subtypes

               -  Double/triple hit lymphomas

               -  Indolent lymphomas transformed to aggressive lymphomas

               -  Follicular lymphomas grade 3B

          -  Patients must have received at least two cycles of anthracycline based chemotherapy
             administered with curative intent and one of the following:

               -  failed to have achieve at least a partial response after 2 or more cycles

               -  failed to achieve a complete response after 6 or more cycles

               -  progressed after an initial response

          -  Patients must be age ≥18 years.

          -  Patients must have at least one site of measurable disease, 1.5 cm in diameter or
             greater.

          -  Patients must have ECOG performance status of 0-2.

          -  Patients must have laboratory test results within these ranges:

               -  Absolute neutrophil count ≥ 1500/mm³

               -  Platelet count ≥ 100,000/mm³

               -  Serum creatinine clearance ≥40 mL/min

               -  Total bilirubin ≤ 1.5x ULN. Higher levels are acceptable if these can be
                  attributed to active hemolysis or ineffective erythropoiesis.

               -  AST (SGOT) and ALT (SGPT) ≤ 2x ULN

          -  Women of childbearing potential must agree to use dual methods of contraception and
             have a negative serum pregnancy test prior to selinexor treatment. 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 must be able to understand and willing to sign a written informed consent
             document.

          -  Patients must be able to adhere to the study visit schedule and other protocol
             requirements.

          -  Patients must not have any serious medical condition, laboratory abnormality, or
             psychiatric illness that would prevent the subject from signing the informed consent
             form.

          -  Patients must not have any condition, including the presence of laboratory
             abnormalities, which places the subject at unacceptable risk if he/she were to
             participate in the study or confounds the ability to interpret data from the study.

        Exclusion Criteria:

          -  Patients with hyperuricemia or other potential signs of tumor lysis syndrome

          -  Patients with more than minimally symptomatic disease (i.e. > grade 1), high tumor
             burden, or other indication for urgent treatment.

          -  Patients who have had prior malignancies (other than B-cell lymphomas) for ≤5 years
             with exception of currently treated basal cell, squamous cell carcinoma of the skin,
             or carcinoma "in situ" of the cervix or breast.

          -  Patients who have had other anti-cancer therapy, including radiation or experimental
             drug or therapy, within 28 days of enrollment.

          -  Patients with known HIV, active hepatitis B, active hepatitis C.

          -  Patients with known central nervous system involvement by lymphoma.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dosage (MTD) of Selinexor/KPT-330 when combined with RICE chemo in a relapsed/refractory aggressive b-cell lymphoma setting.
Time Frame:approximately 24 months
Safety Issue:
Description:The highest dose level at which no more than 1 or 6 patients presents with a dose-limiting toxicity (DLT) during the first 6 cycles of treatment

Secondary Outcome Measures

Measure:Survival of subjects treated with KPT-330 + RICE
Time Frame:approximately 24 months per patient
Safety Issue:
Description:Overall survival of patients enrolled on KPT-330 + RICE
Measure:Progression-Free Survival of subjects treated with KPT-330 + RICE
Time Frame:approximately 24 months per patient
Safety Issue:
Description:Progression-free survival of patients enrolled on KPT-330+RICE
Measure:Number of patients who demonstrate a Response to KPT-330+RICE
Time Frame:approximately 24 months per patient
Safety Issue:
Description:The efficacy (as assessed by clinical response) of the combination of KPT-330 + RICE in patients with Rel/Ref b-cell lymphoma
Measure:Number of patients who undergo stem cell collection after induction therapy with KPT-330 + RICE
Time Frame:approximately 24 months per patient
Safety Issue:
Description:The number of patients who can feasibly undergo a stem cell transplant after treatment with KPT-330+RICE

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Weill Medical College of Cornell University

Trial Keywords

  • DLBCL
  • Aggressive
  • Diffuse
  • Large

Last Updated

December 30, 2019