Safety Study of the Selective Inhibitor of Nuclear Export (SINE) KPT-330 in Patients With Advanced Hematological Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2015 by Karyopharm Therapeutics, Inc
Sponsor:
Information provided by (Responsible Party):
Karyopharm Therapeutics, Inc
ClinicalTrials.gov Identifier:
NCT01607892
First received: May 16, 2012
Last updated: January 13, 2015
Last verified: January 2015
  Purpose

The purpose of this research study are to find out more information such as: the highest dose of KPT-330 that can be given safely, the side effects it may cause, to examine how the body affects the study drug concentrations in the blood (pharmacokinetics or PK), to examine the effects of this study drug on the body (pharmacodynamics or PDn) and to gain some information on its effectiveness in treating cancer.


Condition Intervention Phase
Hematological Malignancies
Drug: KPT-330
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of the Safety, Pharmacokinetics and Pharmacodynamics of Escalating Doses of the Selective Inhibitor of Nuclear Export/SINE™ Compound KPT-330 in Patients With Advanced Hematological Malignancies

Resource links provided by NLM:


Further study details as provided by Karyopharm Therapeutics, Inc:

Primary Outcome Measures:
  • Number of participants with Adverse Events [ Time Frame: 2 and 12 months ] [ Designated as safety issue: Yes ]
    Severity of Adverse Events


Secondary Outcome Measures:
  • Area under the plasma concentration versus time curve (AUC) of KPT-330 [ Time Frame: 2 and 12 months ] [ Designated as safety issue: No ]
    Changes in AUC over time


Estimated Enrollment: 275
Study Start Date: June 2012
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Chronic Hematological Malignancies
This Arm includes patients with "chronic" hematological malignancies.
Drug: KPT-330

Schedule 1 & 2 no longer enrolling

Schedule 3: Starting dose ≥ 30mg/m2, 2X/week on D1 & D3 each week. Total of 8 dose/cycle.

Schedule 4: Starting dose will be ≥ 23mg/m2, 2x/wk on D1 & D2 of each week. Total of 8 doses/cycle.

Schedule 5: Starting dose will be ≥ 30mg/m2, 2x/week on D1 and D4 of each week. Total of 8 doses/cycle.

Schedule 6: Starting dose ≥ 35mg/m2, 2X/week on D1&D3 each week with 20mg Dex on each dosing day. Total of 8 dose/cycle.

Schedule 7: Starting dose will be ≥ 45mg/m2, once a week. Total of 4 doses/cycle.

Schedule 8: Starting dose will be ≥ 45mg/m2, 2x/week during the first 2 weeks on Days 1, 3, 8, and 10, followed by an 11-day treatment free interval in each 3 week cycle. Total of 4 doses/cycle.

Other Name: Selinexor
Experimental: Acute Myeloid Leukemia (AML)
Patients with all types of relapsed/refractory or non-chemotherapy candidate AML, except acute promyelocytic leukemia (APL) will be included in this Arm.
Drug: KPT-330

Schedule 1 & 2 no longer enrolling

Schedule 3: Starting dose ≥ 30mg/m2, 2X/week on D1 & D3 each week. Total of 8 dose/cycle.

Schedule 4: Starting dose will be ≥ 23mg/m2, 2x/wk on D1 & D2 of each week. Total of 8 doses/cycle.

Schedule 5: Starting dose will be ≥ 30mg/m2, 2x/week on D1 and D4 of each week. Total of 8 doses/cycle.

Schedule 6: Starting dose ≥ 35mg/m2, 2X/week on D1&D3 each week with 20mg Dex on each dosing day. Total of 8 dose/cycle.

Schedule 7: Starting dose will be ≥ 45mg/m2, once a week. Total of 4 doses/cycle.

Schedule 8: Starting dose will be ≥ 45mg/m2, 2x/week during the first 2 weeks on Days 1, 3, 8, and 10, followed by an 11-day treatment free interval in each 3 week cycle. Total of 4 doses/cycle.

Other Name: Selinexor
Experimental: Dose Expansion Cohort
Peripheral (PTCL) and Cutaneous (CTCL) T Cell Lymphoma Up to 12 patients with relapsed / refractory PTCL or CTCL will be enrolled in this cohort at a dose of 30mg/m2 twice weekly (Schedule 3).
Drug: KPT-330

Schedule 1 & 2 no longer enrolling

Schedule 3: Starting dose ≥ 30mg/m2, 2X/week on D1 & D3 each week. Total of 8 dose/cycle.

Schedule 4: Starting dose will be ≥ 23mg/m2, 2x/wk on D1 & D2 of each week. Total of 8 doses/cycle.

Schedule 5: Starting dose will be ≥ 30mg/m2, 2x/week on D1 and D4 of each week. Total of 8 doses/cycle.

Schedule 6: Starting dose ≥ 35mg/m2, 2X/week on D1&D3 each week with 20mg Dex on each dosing day. Total of 8 dose/cycle.

Schedule 7: Starting dose will be ≥ 45mg/m2, once a week. Total of 4 doses/cycle.

Schedule 8: Starting dose will be ≥ 45mg/m2, 2x/week during the first 2 weeks on Days 1, 3, 8, and 10, followed by an 11-day treatment free interval in each 3 week cycle. Total of 4 doses/cycle.

Other Name: Selinexor
Experimental: Acute Lymphoblastic Leukemia (B- or T- cell)
This is an expansion cohort for relapsed/refractory ALL
Drug: KPT-330

Schedule 1 & 2 no longer enrolling

Schedule 3: Starting dose ≥ 30mg/m2, 2X/week on D1 & D3 each week. Total of 8 dose/cycle.

Schedule 4: Starting dose will be ≥ 23mg/m2, 2x/wk on D1 & D2 of each week. Total of 8 doses/cycle.

Schedule 5: Starting dose will be ≥ 30mg/m2, 2x/week on D1 and D4 of each week. Total of 8 doses/cycle.

Schedule 6: Starting dose ≥ 35mg/m2, 2X/week on D1&D3 each week with 20mg Dex on each dosing day. Total of 8 dose/cycle.

Schedule 7: Starting dose will be ≥ 45mg/m2, once a week. Total of 4 doses/cycle.

Schedule 8: Starting dose will be ≥ 45mg/m2, 2x/week during the first 2 weeks on Days 1, 3, 8, and 10, followed by an 11-day treatment free interval in each 3 week cycle. Total of 4 doses/cycle.

Other Name: Selinexor
Experimental: Chronic Myelocytic Leukemia (CML)
This is an Expansion cohort for Accelerated or blast crisis phase
Drug: KPT-330

Schedule 1 & 2 no longer enrolling

Schedule 3: Starting dose ≥ 30mg/m2, 2X/week on D1 & D3 each week. Total of 8 dose/cycle.

Schedule 4: Starting dose will be ≥ 23mg/m2, 2x/wk on D1 & D2 of each week. Total of 8 doses/cycle.

Schedule 5: Starting dose will be ≥ 30mg/m2, 2x/week on D1 and D4 of each week. Total of 8 doses/cycle.

Schedule 6: Starting dose ≥ 35mg/m2, 2X/week on D1&D3 each week with 20mg Dex on each dosing day. Total of 8 dose/cycle.

Schedule 7: Starting dose will be ≥ 45mg/m2, once a week. Total of 4 doses/cycle.

Schedule 8: Starting dose will be ≥ 45mg/m2, 2x/week during the first 2 weeks on Days 1, 3, 8, and 10, followed by an 11-day treatment free interval in each 3 week cycle. Total of 4 doses/cycle.

Other Name: Selinexor
Experimental: Multiple Myeloma and Waldenstroms
This is an expansion cohort for only MM and WM patients
Drug: KPT-330

Schedule 1 & 2 no longer enrolling

Schedule 3: Starting dose ≥ 30mg/m2, 2X/week on D1 & D3 each week. Total of 8 dose/cycle.

Schedule 4: Starting dose will be ≥ 23mg/m2, 2x/wk on D1 & D2 of each week. Total of 8 doses/cycle.

Schedule 5: Starting dose will be ≥ 30mg/m2, 2x/week on D1 and D4 of each week. Total of 8 doses/cycle.

Schedule 6: Starting dose ≥ 35mg/m2, 2X/week on D1&D3 each week with 20mg Dex on each dosing day. Total of 8 dose/cycle.

Schedule 7: Starting dose will be ≥ 45mg/m2, once a week. Total of 4 doses/cycle.

Schedule 8: Starting dose will be ≥ 45mg/m2, 2x/week during the first 2 weeks on Days 1, 3, 8, and 10, followed by an 11-day treatment free interval in each 3 week cycle. Total of 4 doses/cycle.

Other Name: Selinexor
Experimental: Non-Hodgkin Lymphoma (NHL)
This is a combination cohort (escalation and expansion) for NHL patients and patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL.)
Drug: KPT-330

Schedule 1 & 2 no longer enrolling

Schedule 3: Starting dose ≥ 30mg/m2, 2X/week on D1 & D3 each week. Total of 8 dose/cycle.

Schedule 4: Starting dose will be ≥ 23mg/m2, 2x/wk on D1 & D2 of each week. Total of 8 doses/cycle.

Schedule 5: Starting dose will be ≥ 30mg/m2, 2x/week on D1 and D4 of each week. Total of 8 doses/cycle.

Schedule 6: Starting dose ≥ 35mg/m2, 2X/week on D1&D3 each week with 20mg Dex on each dosing day. Total of 8 dose/cycle.

Schedule 7: Starting dose will be ≥ 45mg/m2, once a week. Total of 4 doses/cycle.

Schedule 8: Starting dose will be ≥ 45mg/m2, 2x/week during the first 2 weeks on Days 1, 3, 8, and 10, followed by an 11-day treatment free interval in each 3 week cycle. Total of 4 doses/cycle.

Other Name: Selinexor

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Patients with malignancies that are refractory to or who are intolerant of established therapy known to provide clinical benefit for their condition. Patients must not be candidates for anti-tumor regimens known to provide clinical benefit
  2. Arm 1 Dose Escalation Phase: Histologically confirmed diagnosis, and evidence of disease progression, of Multiple Myeloma (MM), Non-Hodgkin's Lymphoma (NHL), Chronic Lymphocytic Leukemia (CLL), or Waldenstrom's Macroglobulinemia (WM) as described below:

Multiple Myeloma (MM): Symptomatic disease previously treated with ≥3 prior regimens (lines of therapy) that included at least one of each of the following: an alkylating agent, an immunomodulatory drug, a proteasome inhibitor, and a steroid. Patients must have measurable disease as defined by at least one of the following:

  1. Serum M-protein ≥ 0.5 g/dL by serum electrophoresis (SPEP) or for IgA myeloma, by quantitative IgA; or
  2. Urinary M-protein excretion at least 200 mg/24 hours; or
  3. Serum Free Light Chain (SFLC) whereby the involved light chain measures ≥ 10 mg/dL and with an abnormal ratio

Non-Hodgkin's Lymphoma (NHL): Advanced indolent or aggressive NHL according to the WHO classification, having been treated with ≥2 prior regimens including rituximab (for B cell NHL only), an alkylating agent, and steroids. Patients with cutaneous T cell lymphoma (CTCL) or Peripheral T Cell Leukemia (PTCL) are excluded from this study.

Chronic Lymphocytic Leukemia (CLL): advanced, relapsed CLL after having received fludarabine (if medically appropriate), an alkylating agent, and rituximab as part of one or more of their previous regimens.

Waldenström's Macroglobulinemia (WM): relapsed WM after at least 2 prior regimens (lines of therapy) that included at least one proteasome inhibitor and at least one steroid.

Arm 1: Dose Expansion Phase:

  • Up to 10 patients with MM or WM: Symptomatic disease previously treated with, and relapsed or refractory to, ≥3 prior regimens (lines of therapy) that included at least one of each of the following: an alkylating agent, an immunomodulatory drug, a proteasome inhibitor, and a steroid. Patients must have measurable disease as defined by at least one of the following:

    1. Serum M-protein ≥ 0.5 g/dL by serum electrophoresis (SPEP) or for IgA myeloma, by quantitative IgA; or
    2. Urinary M-protein excretion at least 200 mg/24 hours; or
    3. Serum Free Light Chain (SFLC) whereby the involved light chain measures ≥ 10 mg/dL and with an abnormal ratio.
  • Up to 15 patients with relapsed or refractory Diffuse Large B Cell Lymphoma (DLBCL):

    1. Biopsy-proven aggressive Diffuse Large B-Cell Lymphoma of any genetic subtype.
    2. Relapsed or refractory to previous therapy for lymphoma.
    3. Must have received at least one prior combination chemotherapy regimen. There is no limit on the number of prior therapies.
    4. Patients must have an autologous stem cell transplant if they were eligible for it.
    5. Patients must have measurable disease on cross sectional imaging that is at least 2 cm in the longest diameter.

Arm 2 Dose Escalation and Expansion Phases: Histologically confirmed diagnosis of AML according to the WHO classification (any subtype except for Acute Promyelocytic Leukemia (APL)) with disease progression after chemotherapy, or not a chemotherapy candidate as defined as:

  • Refractory disease as defined: Persistent disease after at least two induction cycles (e.g., 3+7 and 2+5), or at least one high dose arabinoside-C (Ara-C) containing regimen; or
  • Relapsed AML: unlikely to benefit from chemotherapy (second or subsequent relapse, any relapse patients failing salvage chemotherapy, or patients in first relapse with less than one year disease free interval; or
  • Non-chemotherapy candidates: Previously untreated older adults (> age 60) with at least one of the following risk factors: age >70 years, antecedent hematological disease, non-favorable chromosome analysis.

Dose Expansion Cohort Approximately 25 eligible patients with MM or WM (N=10) and DLBCL (N=15) will be enrolled into the dose expansion cohort in Arm 1 as described above

Approximately 24 eligible patients AML as described in the escalation cohort above will be enrolled into the dose expansion cohort in Arm 2.

Arm 3 Dose Expansion Phase: Histologically confirmed diagnosis of CTCL or PTCL (any subtype) following treatment with at least two prior therapies.

  • PTCL: patients must have relapsed or refractory to at least one prior chemotherapy regimen, and have relapsed from, or are intolerant to, both romidepsin and pralatrexate.
  • CTCL: patients must extensive disease and have relapsed after at least one prior chemotherapy regimen as well as from romidepsin.

    5.All patients on this study must have evidence of progressive disease on study entry. Previously untreated patients who are not chemotherapy candidates on Arm 2 may have advanced disease (without clear progression). There is no upper limit on the number of prior treatments provided all inclusion/exclusion criteria are met.

Exclusion Criteria

  1. Radiation, chemotherapy, or immunotherapy or any other anticancer therapy ≤2 weeks prior to cycle 1 day 1 and mitomycin C and radioimmunotherapy 6 weeks prior to cycle 1 day 1. For CLL and NHL palliative steroids for disease related symptoms are allowed up to 3 days prior to starting therapy. For patients in Arm 2, Hydroxyurea may be given prior to, and during the first cycle of treatment with KPT-330;
  2. Patients with active graft versus host disease after allogeneic stem cell transplantation. At least 3 months must have elapsed since completion of allogeneic stem cell transplantation except for patients with AML, where at least 2 months must have elapsed;
  3. Known active hepatitis A, B, or C infection; or known to be positive for HCV RNA or HBsAg (HBV surface antigen);
  4. Patients with active CNS malignancy. Asymptomatic small lesions are not considered active. Treated lesions may be considered inactive if they are stable for at least 3 months. Patient with malignant cells in their cerebrospinal fluid (CSF) without CNS symptom may be included.
  5. Patients with significantly diseased or obstructed gastrointestinal tract or uncontrolled vomiting or diarrhea.
  6. Grade ≥2 peripheral neuropathy at baseline (within 14 days prior to cycle 1 day 1).
  7. Patients with macular degeneration, uncontrolled glaucoma, or markedly decreased visual acuity.
  8. In the opinion of the investigator, patients who are significantly below their ideal body weight.
  9. Concurrent therapy with approved or investigational anticancer therapeutic other than steroids or hydroxyurea as specified above.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01607892

Contacts
Contact: Michael Kauffman, MD, PhD 508-975-4822 mkauffman@karyopharm.com

Locations
United States, Florida
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact    888-663-3488      
Principal Investigator: Rachid Baz         
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact    617-632-3000      
Principal Investigator: Richard Stone         
United States, Missouri
Washington University School of Medicine Recruiting
St Louis, Missouri, United States, 63110
Contact    314-362-5000      
Principal Investigator: Nina Wagner-Johnston         
United States, New Jersey
Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
Contact    551-996-5900      
Principal Investigator: David Siegel         
United States, New York
Weill Cornell Medical Center Recruiting
New York City, New York, United States, 10065
Contact: Peter Martin    646-962-2064    pem9019@med.cornell.edu   
United States, Ohio
Gabrail Cancer Center Research Recruiting
Canton, Ohio, United States, 44718
Contact    330-492-3345      
Principal Investigator: Nashat Gabrail         
The Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Contact    614-293-8652      
Principal Investigator: John Byrd         
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact    877-691-7274      
Principal Investigator: Michael R. Savona         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact    713-792-2121      
Principal Investigator: Michael Wang         
Canada, Alberta
Tom Baker Cancer Centre Recruiting
Calgary, Alberta, Canada, T2W 4N2
Contact    403-521-3723      
Principal Investigator: Lynn Savoie         
Canada, Ontario
Princess Margaret Hospital Recruiting
Toronto, Ontario, Canada, M5T 2M9
Contact    416 946 2000      
Principal Investigator: John Kuruvilla         
Denmark
Rigshospitalet Recruiting
Copenhagen, Denmark, 2100
Contact    +45 3545 3545      
Principal Investigator: Peter Brown         
Sponsors and Collaborators
Karyopharm Therapeutics, Inc
  More Information

No publications provided by Karyopharm Therapeutics, Inc

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Karyopharm Therapeutics, Inc
ClinicalTrials.gov Identifier: NCT01607892     History of Changes
Other Study ID Numbers: KCP-330-001
Study First Received: May 16, 2012
Last Updated: January 13, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Karyopharm Therapeutics, Inc:
Selinexor
KPT-330
Multiple Myeloma
non-Hodgkin Lymphoma
Chronic Lymphocytic Leukemia
Waldenström's macroglobulinemia
Peripheral T-Cell Lymphoma
Cutaneous T-Cell Lymphoma
Chronic Myelocytic Leukemia
Acute Lymphoblastic Leukemia

ClinicalTrials.gov processed this record on March 26, 2015