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

• Sponsor: Daiichi Sankyo, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01217229
• Collaborator: Plexxikon (Industry)
• Enrollment: 20
• Locations: 6
• Arm: 1
• Actual Duration (Months): 13.8
• Patients Per Site: 3.3
• Patients Per Site Per Month: 0.2

Study Details

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
• 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: Mar 3, 2011
• Actual Primary Completion Date: Apr 26, 2012
• Actual Study Completion Date: Apr 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) [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) [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) [Baseline to 1 year post-dose]

4. Participants With at Least Grade 2 Severity Adverse Events by Preferred Term (Safety Population) [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

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	UCLA Jonsson Comprehensive Cancer Center	Los Angeles	California	United States	90095
2	Northwestern University, The Robert H Lurie Comprehensive Cancer Center	Chicago	Illinois	United States	60611
3	Mayo Clinic	Rochester	Minnesota	United States	55905
4	Nebraska Medical Center	Omaha	Nebraska	United States	68198
5	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065
6	MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• Daiichi Sankyo, Inc.
• Plexxikon

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Daiichi Sankyo, Inc.
• ClinicalTrials.gov Identifier: NCT01217229
• Other Study ID Numbers: PLX108-03
• First Posted: Oct 8, 2010
• Last Update Posted: Jun 30, 2020
• Last Verified: Jun 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Daiichi Sankyo, Inc.: Hodgkin Lymphoma
• Additional relevant MeSH terms: Lymphoma; Hodgkin Disease

Study Results

Participant Flow

Recruitment Details	A total of 20 participants who met all inclusion and no exclusion criteria were enrolled and received treatment at 6 clinic sites in the United States.

Arm/Group Title	PLX3397
Arm/Group Description	Participants received PLX3397 administered once or twice daily with continuous dosing at 900 mg/day.
Period Title: Overall Study
STARTED	20
COMPLETED	0
NOT COMPLETED	20

Baseline Characteristics

Arm/Group Title	PLX3397
Arm/Group Description	Participants received PLX3397 administered once or twice daily with continuous dosing at 900 mg/day.
Overall Participants	20
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	17 85%
>=65 years	3 15%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40.9 (19.05)
Sex: Female, Male (Count of Participants)
Female	11 55%
Male	9 45%
Region of Enrollment (participants) [Number]
United States	20 100%

Outcome Measures

1. Primary Outcome

Title	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)
Description	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).
Time Frame	Baseline to 1 year postdose

Outcome Measure Data

Analysis Population Description

Progression-free survival was assessed in the Modified Intent-to-Treat population.

Arm/Group Title	PLX3397
Arm/Group Description	Participants received PLX3397 administered once or twice daily with continuous dosing at 900 mg/day.
Measure Participants	20
Median (Inter-Quartile Range) [days]	56

2. Primary Outcome

Title	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)
Description	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.
Time Frame	Baseline to Cycles 3, 5, 7, 10, and 13, up to 1 year postdose

Outcome Measure Data

Analysis Population Description

Tumor response was assessed in the Modified Intent-to-Treat population.

Arm/Group Title	PLX3397
Arm/Group Description	Participants received PLX3397 administered once or twice daily with continuous dosing at 900 mg/day.
Measure Participants	20
Overall: Target tumor response (CR+PR)	1 5%
Overall: Target tumor DCR (CR+PR+SD)	4 20%
Overall: Complete response (CR)	0 0%
Overall: Partial response (PR)	1 5%
Overall: Stable disease (SD)	3 15%
Overall: Relapsed disease or progressive disease	13 65%
Cycle 3: Target tumor response (CR+PR)	0 0%
Cycle 3: Target tumor DCR (CR+PR+SD)	4 20%
Cycle 3: Complete response (CR)	0 0%
Cycle 3: Partial response (PR)	0 0%
Cycle 3: Stable disease (SD)	4 20%
Cycle 3: Relapsed disease or progressive disease	1 5%
Cycle 5: Target tumor response (CR+PR)	0 0%
Cycle 5: Target tumor DCR (CR+PR+SD)	1 5%
Cycle 5: Complete response (CR)	0 0%
Cycle 5: Partial response (PR)	0 0%
Cycle 5: Stable disease (SD)	1 5%
Cycle 5: Relapsed disease or progressive disease	0 0%
Cycle 7: Target tumor response (CR+PR)	1 5%
Cycle 7: Target tumor DCR (CR+PR+SD)	1 5%
Cycle 7: Complete response (CR)	0 0%
Cycle 7: Partial response (PR)	1 5%
Cycle 7: Stable disease (SD)	0 0%
Cycle 7: Relapsed disease or progressive disease	0 0%
Cycle 10: Target tumor response (CR+PR)	1 5%
Cycle 10: Target tumor DCR (CR+PR+SD)	1 5%
Cycle 10: Complete response (CR)	0 0%
Cycle 10: Partial response (PR)	1 5%
Cycle 10: Stable disease (SD)	0 0%
Cycle 10: Relapsed disease or progressive disease	0 0%
Cycle 13: Target tumor response (CR+PR)	1 5%
Cycle 13: Target tumor DCR (CR+PR+SD)	1 5%
Cycle 13: Complete response (CR)	0 0%
Cycle 13: Partial response (PR)	1 5%
Cycle 13: Stable disease (SD)	0 0%
Cycle 13: Relapsed disease or progressive disease	0 0%

3. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Adverse events were assessed in the Safety Analysis population.

Arm/Group Title	PLX3397
Arm/Group Description	Participants received PLX3397 administered once or twice daily with continuous dosing at 900 mg/day.
Measure Participants	20
At least 1 adverse event	20 100%
Anaemia	6 30%
Thrombocytopenia	6 30%
Diarrhoea	2 10%
Nausea	2 10%
Vomiting	2 10%
Chills	2 10%
Fatigue	8 40%
Pyrexia	4 20%
Aspartate aminotransferase increased	2 10%
Blood lactate dehydrogenase increased	5 25%
Decreased appetite	3 15%
Back pain	2 10%
Dizziness	2 10%
Headache	2 10%
Cough	3 15%
Dyspnoea	5 25%
Productive cough	2 10%
Hair colour changes	8 40%
Rash	5 25%

4. Primary Outcome

Title	Participants With at Least Grade 2 Severity Adverse Events by Preferred Term (Safety Population)
Description	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).
Time Frame	Baseline to 1 year postdose

Outcome Measure Data

Analysis Population Description

Adverse events were assessed in the Safety Analysis population.

Arm/Group Title	PLX3397
Arm/Group Description	Participants received PLX3397 administered once or twice daily with continuous dosing at 900 mg/day.
Measure Participants	20
At least 1 Grade 2 adverse event	13 65%
At least 1 Grade 3 adverse event	5 25%
Grade 2 Anaemia	6 30%
Grade 2 Neutropenia	1 5%
Grade 3 Neutropenia	1 5%
Grade 2 Thrombocytopenia	1 5%
Grade 3 Thrombocytopenia	1 5%
Grade 2 Fatigue	5 25%
Grade 2 Pyrexia	2 10%
Grade 3 Lung infection	1 5%
Grade 2 Pneumonia	1 5%
Grade 3 Blood alkaline phosphatase	1 5%
Grade 2 Blood lactate dehydrogenase increased	2 10%
Grade 3 Neutrophil count decreased	3 15%
Grade 2 Decreased appetite	1 5%
Grade 2 Muscular weakness	1 5%
Grade 2 Squamous cell carcinoma	1 5%
Grade 3 Syncope	1 5%
Grade 2 Anxiety	1 5%
Grade 2 Dyspnoea	2 10%
Grade 2 Erythema multiforme	1 5%
Grade 2 Rash	2 10%
Grade 3 Rash	1 5%
Grade 2 Skin exfoliation	1 5%

Adverse Events

Time Frame	Adverse events were collected from study enrollment up to 1 year post dose.
Arm/Group Title	PLX3397
Arm/Group Description	Participants received PLX3397 administered once or twice daily with continuous dosing at 900 mg/day.
All Cause Mortality
	PLX3397
	Affected / at Risk (%)	# Events
Total	0/20 (0%)
Serious Adverse Events
	PLX3397
	Affected / at Risk (%)	# Events
Total	1/20 (5%)
General disorders
Pyrexia	1/20 (5%)
Infections and infestations
Lung infection	1/20 (5%)
Other (Not Including Serious) Adverse Events
	PLX3397
	Affected / at Risk (%)	# Events
Total	20/20 (100%)
Blood and lymphatic system disorders
Anaemia	6/20 (30%)
Thrombocytopenia	6/20 (30%)
Leukopenia	1/20 (5%)
Neutropenia	1/20 (5%)
Ear and labyrinth disorders
Ear pain	1/20 (5%)
Eye disorders
Eye swelling	1/20 (5%)
Eyelid oedema	1/20 (5%)
Gastrointestinal disorders
Abdominal distension	1/20 (5%)
Abdominal pain	1/20 (5%)
Constipation	1/20 (5%)
Diarrhoea	2/20 (10%)
Gastrooesophageal reflux disease	1/20 (5%)
Nausea	2/20 (10%)
Vomiting	2/20 (10%)
Asthenia	1/20 (5%)
Chills	2/20 (10%)
Face odema	1/20 (5%)
Fatigue	8/20 (40%)
Pyrexia	4/20 (20%)
General disorders
Fatigue	8/20 (40%)
Infections and infestations
Clostridial infection	1/20 (5%)
Herpes zoster	1/20 (5%)
Lung infection	1/20 (5%)
Nasopharyngitis	1/20 (5%)
Pneumonia	1/20 (5%)
Investigations
Alanine aminotransferase increased	1/20 (5%)
Aspartate aminotransferase increased	2/20 (10%)
Blood alkaline phosphatase	1/20 (5%)
Blood lactate dehydrogenase increased	5/20 (25%)
Neutrophil count decreased	1/20 (5%)
Metabolism and nutrition disorders
Decreased appetite	3/20 (15%)
Hyperglycaemia	1/20 (5%)
Hyperkalaemia	1/20 (5%)
Musculoskeletal and connective tissue disorders
Back pain	2/20 (10%)
Joint swelling	1/20 (5%)
Muscular weakness	1/20 (5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma	1/20 (5%)
Nervous system disorders
Balance disorder	1/20 (5%)
Dizziness	2/20 (10%)
Dysgeusia	1/20 (5%)
Headache	2/20 (10%)
Lethargy	1/20 (5%)
Neuropathy peripheral	1/20 (5%)
Syncope	1/20 (5%)
Tremor	1/20 (5%)
Psychiatric disorders
Anxiety	1/20 (5%)
Hallucination	1/20 (5%)
Insomnia	1/20 (5%)
Reproductive system and breast disorders
Menstruation irregular	1/20 (5%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	5/20 (25%)
Cough	3/20 (15%)
Dyspnoea	5/20 (25%)
Haemoptysis	1/20 (5%)
Pleuritic pain	1/20 (5%)
Productive cough	2/20 (10%)
Skin and subcutaneous tissue disorders
Hair depigmentation	8/20 (40%)
Rash	5/20 (25%)
Dry skin	1/20 (5%)
Erythema multiforme	1/20 (5%)
Hair colour changes	8/20 (40%)
Pruritus	1/20 (5%)
Skin exfoliation	1/20 (5%)
Skin hypopigmentation	1/20 (5%)
Swelling face	1/20 (5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.