Safety and Efficacy Study of PLX3397 in Adults With Relapsed or Refractory Hodgkin Lymphoma

• ClinicalTrials.gov Identifier: NCT01217229
• Recruitment Status: Completed
• First Posted: October 8, 2010
• Results First Posted: March 15, 2013
• Last Update Posted: June 30, 2020
• Sponsor: Daiichi Sankyo, Inc.
• Collaborator: Plexxikon
• Information provided by (Responsible Party): Daiichi Sankyo, Inc.

Study Description

Brief Summary:

PLX3397 is a selective inhibitor of Fms, Kit, and oncogenic Flt3 activity.The primary objective of this study is to evaluate the efficacy, as measured by overall response rate, of orally administered PLX3397 in patients with relapsed or refractory classical Hodgkin lymphoma (HL). Secondary objectives include safety, the duration of response, the disease control rate, progression free survival, and how the drug affects your body.

Condition or disease	Intervention/treatment	Phase
Hodgkin Lymphoma	Drug: PLX3397	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Safety and Efficacy Study of Orally Administered PLX3397 in Adults With Relapsed or Refractory Hodgkin Lymphoma
• Actual Study Start Date: March 3, 2011
• Actual Primary Completion Date: April 26, 2012
• Actual Study Completion Date: April 26, 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: PLX3397	Drug: PLX3397; Capsules administered once or twice daily, continuous dosing. Subjects will begin with 900 mg/day, but should safety data allow in our PLX108-01 study, subject may dose at 1200 mg/day.

Outcome Measures

Primary Outcome Measures :

1. Progression-Free Survival According to the Cheson Criteria by Kaplan-Meier Analysis Following Orally Administered PLX3397 in Adults With Relapsed or Refractory Hodgkin Lymphoma (Modified Intent-to-Treat Population) [ Time Frame: Baseline to 1 year postdose ]
   Progression-free survival was assessed by Kaplan Meier analysis and was defined as the number of days from the first day of treatment to the date of first documented disease progression or date of death (whichever occurred first).
2. Summary of Overall Tumor Response and By Cycle Following Orally Administered PLX3397 in Adults With Relapsed or Refractory Hodgkin Lymphoma (Modified Intent-to-Treat Population) [ Time Frame: Baseline to Cycles 3, 5, 7, 10, and 13, up to 1 year postdose ]
   Subjects were monitored for response and disease progression with contrast Computed tomography (CT) /18Fluorodeoxyglucose (FDG)-positron emission tomography (PET) scans every two cycles. Each cycle is 28 days. Response to treatment as defined by Cheson criteria was reported via descriptive statistics. Target tumor response is Complete Response (CR) + Partial Response (PR) and target tumor disease control rate (CR + PR + Stable Disease (SD)) are reported. Per Cheson Criteria, CR is disappearance of all evidence of disease; Partial Response is regression of measurable disease and no new sites (≥50% decrease in sum of product diameters of up to 6 largest dominant masses and splenic/liver nodules), and no increase in size of other nodes/liver/spleen; reduction in target lesions, no growth of non-target or new lesions; Progression is any new lesion or increase by ≥50% of previously involved sites from the nadir.
3. Participants With Treatment-Emergent Adverse Events Occurring at a Frequency of ≥10% in Any Preferred Term (Safety Population) [ Time Frame: Baseline to 1 year post-dose ]
4. Participants With at Least Grade 2 Severity Adverse Events by Preferred Term (Safety Population) [ Time Frame: Baseline to 1 year postdose ]
   Grade 2 adverse events were defined as events that were moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Male or female patients ≥18 years old
2. Pathologic confirmation of relapsed or refractory classical Hodgkin lymphoma, with archival or fresh tissue available for retrospective analysis.
3. Patients must have progressed after-or been ineligible for-autologous stem cell transplantation. Patients who received a prior allogeneic stem cell transplantation are eligible if they have no evidence of graft versus host disease (GVHD) and have been off immunosuppression for at least 3 months prior to Cycle 1 Day 1 (C1D1).
4. Documented disease that is radiographically measurable (≥2 cm in the largest transverse dimension).
5. Patients must have discontinued any previous monoclonal antibody, radioimmunotherapy, or cytotoxic chemotherapy at least 28 days prior to C1D1 and must have recovered fully from the side effects of that treatment prior to beginning study treatment.
6. Women of child-bearing potential must have a negative pregnancy test within 7 days of initiation of dosing and must agree to use an acceptable method of birth control while on study drug and for 3 months after the last dose. Women of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for ≥1 year. Men of child-bearing potential must also agree to use an acceptable method of birth control while on study drug.
7. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
8. Adequate hematologic, hepatic, and renal function (absolute neutrophil count ≥1.0 x 109/L, Hgb >9 g/dL, platelet count ≥50 x 109/L, Aspartate Transaminase (AST) / Alanine Transaminase (ALT) ≤2.5x Upper limit of normal (ULN), creatinine ≤1.5x ULN)
9. Willing and able to provide written informed consent prior to any study related procedures and to comply with all study requirements

Exclusion Criteria:

1. Investigational drug use within 28 days of the first dose of PLX3397
2. History or clinical evidence of central nervous system, meningeal, or epidural disease including brain metastasis
3. Patients with another active cancer [excluding basal cell carcinoma or cervical intraepithelial neoplasia (cervical carcinoma in situ) or melanoma in situ]. Prior history of other cancer is allowed, as long as there was no active disease within the prior 5 years.
4. Patients with uncontrolled intercurrent illness, an active or uncontrolled infection, or a fever >38.5˚C (not due to tumor fever) on C1D1
5. Refractory nausea and vomiting, malabsorption, biliary shunt, or significant bowel resection that would preclude adequate absorption
6. Patients with serious illnesses, medical conditions, or other medical history including abnormal laboratory results, which in the investigator's opinion would be likely to interfere with a patient's participation in the study, or with the interpretation of the results
7. Women of child-bearing potential who are pregnant or breast feeding
8. Corrected QT interval (QTc) ≥450 msec.

Contacts and Locations

Locations

United States, California

UCLA Jonsson Comprehensive Cancer Center

Los Angeles, California, United States, 90095

United States, Illinois

Northwestern University, The Robert H Lurie Comprehensive Cancer Center

Chicago, Illinois, United States, 60611

United States, Minnesota

Mayo Clinic

Rochester, Minnesota, United States, 55905

United States, Nebraska

Nebraska Medical Center

Omaha, Nebraska, United States, 68198

United States, New York

Memorial Sloan-Kettering Cancer Center

New York, New York, United States, 10065

United States, Texas

MD Anderson Cancer Center

Houston, Texas, United States, 77030

Sponsors and Collaborators

Daiichi Sankyo, Inc.

Plexxikon

More Information

• Responsible Party: Daiichi Sankyo, Inc.
• ClinicalTrials.gov Identifier: NCT01217229
• Other Study ID Numbers: PLX108-03
• First Posted: October 8, 2010
• Results First Posted: March 15, 2013
• Last Update Posted: June 30, 2020
• Last Verified: June 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)
• Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• URL: https://vivli.org/ourmember/daiichi-sankyo/

Keywords provided by Daiichi Sankyo, Inc.:

Hodgkin Lymphoma

Additional relevant MeSH terms:

Lymphoma; Hodgkin Disease; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases