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

NCT02471911 | Completed Phase 1

• 1 other identifier: 1502015891
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Diffuse Large B-Cell Lymphoma

Keywords

DLBCL; Aggressive; Diffuse; Large

Outcome Measures

Primary Outcomes (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

  approximately 24 months

Secondary Outcomes (4)

• Survival of subjects treated with KPT-330 + RICE

  approximately 24 months per patient

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

  approximately 24 months per patient

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

  approximately 24 months per patient

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

  approximately 24 months per patient

Study Arms (1)

All subjects

EXPERIMENTAL

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; Drug: Rituximab; Drug: Etoposide; Drug: Carboplatin; Drug: Ifosfamide; Drug: Dexamethasone

Interventions

KPT-330 DRUG

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.

Also known as: Selinexor

All subjects

Rituximab DRUG

IV Rituximab 375 mg/m2 on D1

Also known as: Rituxan

All subjects

Etoposide DRUG

IV Etoposide 100 mg/m2 on D1-3

All subjects

Carboplatin DRUG

IV Carboplatin AUC 5 on D2

All subjects

Ifosfamide DRUG

IV Ifosfamide 5 g/m2 on D2

All subjects

Dexamethasone DRUG

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

All subjects

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Karyopharm Therapeutics Inc: collaborator
• The Leukemia and Lymphoma Society: collaborator
• FDA Office of Orphan Products Development: collaborator

Study Sites (1)

Weill Cornell Medical College

New York, New York, 10021, United States

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Aggression

Interventions

selinexor; Rituximab; Etoposide; Carboplatin; Ifosfamide; Dexamethasone

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Aberrant Motor Behavior in Dementia; Behavioral Symptoms; Behavior; Social Behavior

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Coordination Complexes; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated

Study Officials

• Peter Martin, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2015
• First Posted: June 15, 2015
• Study Start: December 11, 2015
• Primary Completion: October 31, 2019
• Study Completion: October 14, 2021
• Last Updated: April 12, 2022

Record last verified: 2022-04

Locations

US (1)