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Diffuse Large B-Cell LymphomaPhase 1KPT-330+RICENCT02471911

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

A Phase 1 study testing KPT-330, Rituximab and Etoposide in people with Diffuse Large B-Cell Lymphoma, run by Weill Medical College of Cornell University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Diffuse Large B-Cell Lymphoma
What is being tested?
KPT-330, Rituximab and Etoposide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
1 siteUnited States
Study dates
11 Dec 2015to 14 Oct 2021
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
Show all 25Show fewer
  • 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.

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Weill Cornell Medical College

    New York, New York, 10021

Other trials in United States

About this study

Official title: A Phase I Investigator-Initiated Study of Selinexor (KPT-330) Plus RICE in Patients With Relapsed or Refractory Aggressive B-cell Lymphomas

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).

Read the 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.

Being tested
KPT-330, Rituximab, Etoposide, Carboplatin, Ifosfamide
Keywords
DLBCL, Aggressive, Diffuse, Large
Medical subject headings
Lymphoma, Large B-Cell, Diffuse, Aggression

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • KPT-330Drug

    Also called Selinexor

    KPT-330 administered orally on days -5 and -3 prior to starting chemotherapy. Once chemotherapy starts, KPT-330 will be administered on days 1, 3, and 5 of each cycle. Dose levels will range from 20 mg to 100mg with a standard 3+3 escalation schema.

  • RituximabDrug

    Also called Rituxan

    IV Rituximab 375 mg/m2 on D1

  • EtoposideDrug

    IV Etoposide 100 mg/m2 on D1-3

  • CarboplatinDrug

    IV Carboplatin AUC 5 on D2

  • IfosfamideDrug

    IV Ifosfamide 5 g/m2 on D2

  • DexamethasoneDrug

    20 mg qd on Days -5 and -3. 20 mg qd on Days 1-5

Study groups in NCT02471911
Study groupRoleWhat they receive
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.
Receives: Drug: KPT-330; Drug: Rituximab; Drug: Etoposide; Drug: Carboplatin; Drug: Ifosfamide; Drug: Dexamethasone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dosage (MTD) of Selinexor/KPT-330 when combined with RICE chemo in a relapsed/refractory aggressive b-cell lymphoma setting.

    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

    Measured: approximately 24 months

Secondary outcomes (4)

  1. Survival of subjects treated with KPT-330 + RICE

    Overall survival of patients enrolled on KPT-330 + RICE

    Measured: approximately 24 months per patient

  2. Progression-Free Survival of subjects treated with KPT-330 + RICE

    Progression-free survival of patients enrolled on KPT-330+RICE

    Measured: approximately 24 months per patient

  3. Number of patients who demonstrate a Response to KPT-330+RICE

    The efficacy (as assessed by clinical response) of the combination of KPT-330 + RICE in patients with Rel/Ref b-cell lymphoma

    Measured: approximately 24 months per patient

  4. Number of patients who undergo stem cell collection after induction therapy with KPT-330 + RICE

    The number of patients who can feasibly undergo a stem cell transplant after treatment with KPT-330+RICE

    Measured: approximately 24 months per patient

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Jun 2015 (estimated)
  2. Study start11 Dec 2015
  3. Primary completion31 Oct 2019
  4. Study completion14 Oct 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02471911
Sponsor's protocol ID
1502015891
Acronym
KPT-330+RICE
Status last verified
Apr 2022
First submitted
11 Jun 2015
Last updated
12 Apr 2022
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing KPT-330, Rituximab and Etoposide in people with Diffuse Large B-Cell Lymphoma, run by Weill Medical College of Cornell University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02471911.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Apr 2022.

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