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

This study is currently recruiting participants.
Verified February 2017 by Weill Medical College of Cornell University
Sponsor:
ClinicalTrials.gov Identifier:
NCT02471911
First Posted: June 15, 2015
Last Update Posted: February 7, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Karyopharm Therapeutics Inc
Information provided by (Responsible Party):
Weill Medical College of Cornell University
  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).

Condition Intervention Phase
Diffuse Large B-Cell Lymphoma Drug: KPT-330 Drug: Rituximab Drug: Etoposide Drug: Carboplatin Drug: Ifosfamide Drug: Dexamethasone Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Investigator-Initiated Study of Selinexor (KPT-330) Plus RICE in Patients With Relapsed or Refractory Aggressive B-cell Lymphomas

Resource links provided by NLM:


Further study details as provided by Weill Medical College of Cornell University:

Primary Outcome Measures:
  • 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 ]
    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:
  • Survival of subjects treated with KPT-330 + RICE [ Time Frame: approximately 24 months per patient ]
    Overall survival of patients enrolled on KPT-330 + RICE

  • Progression-Free Survival of subjects treated with KPT-330 + RICE [ Time Frame: approximately 24 months per patient ]
    Progression-free survival of patients enrolled on KPT-330+RICE

  • Number of patients who demonstrate a Response to KPT-330+RICE [ Time Frame: approximately 24 months per patient ]
    The efficacy (as assessed by clinical response) of the combination of KPT-330 + RICE in patients with Rel/Ref b-cell lymphoma

  • Number of patients who undergo stem cell collection after induction therapy with KPT-330 + RICE [ Time Frame: approximately 24 months per patient ]
    The number of patients who can feasibly undergo a stem cell transplant after treatment with KPT-330+RICE


Estimated Enrollment: 18
Study Start Date: November 2015
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: All subjects

All 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.

Drug: KPT-330
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.
Other Name: Selinexor
Drug: Rituximab
IV Rituximab 375 mg/m2 on D1
Other Name: Rituxan
Drug: Etoposide
IV Etoposide 100 mg/m2 on D1-3
Drug: Carboplatin
IV Carboplatin AUC 5 on D2
Drug: Ifosfamide
IV Ifosfamide 5 g/m2 on D2
Drug: Dexamethasone
20 mg qd on Days -5 and -3. 20 mg qd on Days 1-5

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02471911


Contacts
Contact: Amelyn Rodriguez, RN (212) 746-1362 amr2017@med.cornell.edu
Contact: Rita Gazivoda, RN 212-746-0702 rig9021@med.cornell.edu

Locations
United States, New York
Weill Cornell Medical College Recruiting
New York, New York, United States, 10021
Contact: Amelyn Rodriguez, RN    212-746-1362      
Contact: Rita Gazivoda, RN    212-746-0702      
Sponsors and Collaborators
Weill Medical College of Cornell University
Karyopharm Therapeutics Inc
Investigators
Principal Investigator: Peter Martin, MD Weill Medical College of Cornell University
  More Information

Responsible Party: Weill Medical College of Cornell University
ClinicalTrials.gov Identifier: NCT02471911     History of Changes
Other Study ID Numbers: 1502015891
First Submitted: June 11, 2015
First Posted: June 15, 2015
Last Update Posted: February 7, 2017
Last Verified: February 2017

Keywords provided by Weill Medical College of Cornell University:
DLBCL
Aggressive
Diffuse
Large

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Aggression
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Behavioral Symptoms
Dexamethasone acetate
Dexamethasone
Etoposide phosphate
Isophosphamide mustard
Carboplatin
Rituximab
Etoposide
Ifosfamide
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists