Enzalutamide in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma

• Sponsor: University of Washington (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02489123
• Collaborator: National Cancer Institute (NCI) (NIH), National Comprehensive Cancer Network (Other)
• Enrollment: 8
• Location: 1
• Arm: 1
• Actual Duration (Months): 58.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This pilot clinical trial studies enzalutamide in treating patients with mantle cell lymphoma that has returned after a period of improvement (relapsed) or has not responded to previous treatment (refractory). Androgens can cause the growth of cancer cells. Antihormone therapy, such as enzalutamide, may lessen the amount of androgen made by the body.

Condition or Disease	Intervention/Treatment	Phase
Ann Arbor Stage I Mantle Cell Lymphoma; Ann Arbor Stage II Mantle Cell Lymphoma; Ann Arbor Stage III Mantle Cell Lymphoma; Ann Arbor Stage IV Mantle Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Mantle Cell Lymphoma	Drug: Enzalutamide; Other: Laboratory Biomarker Analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Perform a preliminary assessment of the efficacy of single-agent enzalutamide, based on overall response rate, in subjects with relapsed/refractory mantle cell lymphoma (MCL) or previously untreated MCL.

SECONDARY OBJECTIVES:

1. To evaluate the duration of disease control (progression free survival) in patients with MCL treated with enzalutamide.

2. To evaluate the safety profile of enzalutamide in MCL.

3. To gain preliminary data on clinical activity and toxicity of this regimen in male versus (vs.) female patients.

OUTLINE:

Patients receive enzalutamide orally (PO) once daily (QD). Courses 1-3 repeat every 4 weeks (28 days) and subsequent courses repeat every 12 weeks (84 days) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for up to 5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Androgen Receptor Targeting in Mantle Cell Lymphoma: A Pilot Trial of Enzalutamide
• Actual Study Start Date: Aug 11, 2015
• Actual Primary Completion Date: Jun 16, 2020
• Actual Study Completion Date: Jun 16, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (enzalutamide) Patients receive enzalutamide PO QD. Courses 1-3 repeat every 4 weeks (28 days) and subsequent courses repeat every 12 weeks (84 days) in the absence of disease progression or unacceptable toxicity.	Drug: Enzalutamide; Given PO; Other Names: ASP9785 MDV3100 Xtandi ; Other: Laboratory Biomarker Analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Best Overall Response Rate (ORR) Including Complete Response (CR) and Partial Response (PR) as Measured by Standard Criteria [Up to 5 years]

   An ORR of 20% (4 or more responses among 20 patients) will be taken as a benchmark for success for the primary endpoint of this pilot study. Evaluation of response is per standard NCI Response Criteria Cheson 2014 and assessed by PET-CT; CR = complete metabolic response, PR = decrease by more the 50% in the sum of the product of the perpendicular diameters.

Secondary Outcome Measures

1. Time to Treatment Failure [From the first treatment administration to the first time to treatment failure, assessed up to 5 years]

2. Progression-free Survival [From first study drug administration to the first occurrence of disease progression or death from any cause, assessed up to 5 years]

   Kaplan-Meier methodology will be used to estimate event-free curves and corresponding quartiles (including the median).

3. Overall Survival [Up to 5 years]

4. Number of Participants With One or More Adverse Events, Measured by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 [Up to 30 days after study treatment completion, an average of 18 weeks.]

5. Disease Control Rate (CR + PR + Stable Disease [SD] > 3 Months) [Up to 5 years]

   The count of participants who achieved a CR, PR, or SD for greater than 3 months.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients must have histologically confirmed relapsed/refractory or previously untreated mantle cell lymphoma (any stage)

• Patients with untreated MCL should be asymptomatic or minimally symptomatic from their MCL and without aggressive clinicopathological features that would otherwise warrant immediate intensive therapy; these will generally be patients who qualify for an initial period of "watch and wait" per clinical discretion

• Patients must have metabolically active (positron emission tomography [PET] scan positive) measurable disease (defined as lesions greater than 1.5 cm long axis that can be accurately measured in two dimensions by computed tomography [CT])

• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

• Absolute neutrophil count (ANC) >= 1000/mm^{3 or >= 750/mm}3 in the setting of marrow involvement by disease (independent of growth factor or transfusion support)

• Platelets >= 50,000/mm^{3 or >= 30,000/mm}3 in the setting of marrow involvement by disease or splenomegaly due to disease (independent of growth factor or transfusion support)

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x upper limit of normal (ULN)

• Total bilirubin =< 1.5 x ULN unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin

• Creatinine clearance (CrCl) >= 30 mL/min (as calculated by Cockcroft-Gault equation)

• All patients must be informed of the investigational nature of this study and have given written consent in accordance with institutional and federal guidelines; patient must sign an informed consent document indicating that they understand the purpose of and procedures required for the study, and are willing to participate in and comply with the guidelines of the study

• Women of childbearing potential and men who are sexually active must affirm they are practicing a highly effective method of barrier birth control during and after the study consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials; men must agree to not donate sperm during or after the study; these restrictions apply throughout the treatment period and for three months after the last dose of enzalutamide

• Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [beta-hCG]) or urine pregnancy test at screening; women who are pregnant or breastfeeding are ineligible for this study

Exclusion Criteria:

• Uncontrolled illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements within 6 months of enrollment

• Known active central nervous system lymphoma

• Known clinically significant heart disease as evidenced by:

• Myocardial infarction within 6 months of enrollment

• Uncontrolled angina within 6 months of enrollment

• Congestive heart failure New York Heart Association (NYHA) class III or IV, or a history of congestive heart failure NYHA class III or IV in the past, unless a screening echocardiogram (ECHO) or multi-gated acquisition scan (MUGA) within 3 months results in a left ventricular ejection fraction >= 45%

• Clinically significant ventricular arrhythmias

• History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place

• Bradycardia as indicated by a heart rate < 50 beats per minute at screening visit

• Hypotension as indicated by systolic blood pressure (SBP) =< 85 on 2 consecutive measurements at screening visit

• Uncontrolled hypertension as indicated by SBP > 170 mmHg or diastolic blood pressure (DBP) > 105 mmHg on 2 consecutive measurements at screening visit

• Child Pugh class C hepatic dysfunction

• History of seizures

• Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of enzalutamide, or put the study outcomes at undue risk

• Patients with other prior malignancies except for adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, breast or cervical cancer in situ, or other cancer from which the patient has been disease-free for 5 years or greater, unless approved by the protocol investigator / lead-sub-investigator

• Chemotherapy, immunotherapy, biologically targeted therapy, other investigational agent, or radiation therapy within 3 weeks of initiation of enzalutamide therapy; for patients with objectively progressive disease on a Bruton tyrosine kinase (BTK)-targeting agent whom in the opinion of the investigator would not tolerate a 21 day washout period, a > 5 half-lives washout period will be allowed

• Prior allogeneic transplant with graft-versus-host disease (GVHD) requiring ongoing immunosuppressive therapy

• Human immunodeficiency virus (HIV)-positive individuals on combination antiretroviral therapy are ineligible

• Ongoing treatment with hormonal agents (e.g. finasteride, dutasteride, ketoconazole, hormonal birth control, estrogen replacement therapy, testosterone replacement therapy) or herbal products that may have hormonal activity (saw palmetto, black cohosh); patients taking these agents are eligible for screening, but must be willing to undergo a washout period of 4 weeks prior to starting study treatment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington	United States	98109

Sponsors and Collaborators

• University of Washington
• National Cancer Institute (NCI)
• National Comprehensive Cancer Network

Investigators

• Principal Investigator: Ajay Gopal, Fred Hutch/University of Washington Cancer Consortium

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 26, 2020

More Information

Publications

None provided.

• Responsible Party: Ajay Gopal, Professor, Department of Medicine, Division of Oncology; Director, Hematologic Malignancies Medical Oncology, University of Washington
• ClinicalTrials.gov Identifier: NCT02489123
• Other Study ID Numbers: 9340; NCI-2015-00947; 9340; P30CA015704; RG1715046
• First Posted: Jul 2, 2015
• Last Update Posted: Aug 10, 2021
• Last Verified: Jul 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Mantle-Cell

Study Results

Participant Flow

Arm/Group Title	Treatment (Enzalutamide)
Arm/Group Description	Patients receive enzalutamide PO QD. Courses 1-3 repeat every 4 weeks (28 days) and subsequent courses repeat every 12 weeks (84 days) in the absence of disease progression or unacceptable toxicity. Enzalutamide: Given PO Laboratory Biomarker Analysis: Correlative studies
Period Title: Overall Study
STARTED	8
COMPLETED	8
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (Enzalutamide)
Arm/Group Description	Patients receive enzalutamide PO QD. Courses 1-3 repeat every 4 weeks (28 days) and subsequent courses repeat every 12 weeks (84 days) in the absence of disease progression or unacceptable toxicity. Enzalutamide: Given PO Laboratory Biomarker Analysis: Correlative studies
Overall Participants	8
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	6 75%
>=65 years	2 25%
Age (Years) [Median (Full Range) ]
Median (Full Range) [Years]	60
Sex: Female, Male (Count of Participants)
Female	2 25%
Male	6 75%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	8 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 12.5%
White	7 87.5%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	8 100%

Outcome Measures

1. Primary Outcome

Title	Best Overall Response Rate (ORR) Including Complete Response (CR) and Partial Response (PR) as Measured by Standard Criteria
Description	An ORR of 20% (4 or more responses among 20 patients) will be taken as a benchmark for success for the primary endpoint of this pilot study. Evaluation of response is per standard NCI Response Criteria Cheson 2014 and assessed by PET-CT; CR = complete metabolic response, PR = decrease by more the 50% in the sum of the product of the perpendicular diameters.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Enzalutamide)
Arm/Group Description	Patients receive enzalutamide PO QD. Courses 1-3 repeat every 4 weeks (28 days) and subsequent courses repeat every 12 weeks (84 days) in the absence of disease progression or unacceptable toxicity. Enzalutamide: Given PO Laboratory Biomarker Analysis: Correlative studies
Measure Participants	7
Count of Participants [Participants]	0 0%

2. Secondary Outcome

Title	Time to Treatment Failure
Time Frame	From the first treatment administration to the first time to treatment failure, assessed up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Enzalutamide)
Arm/Group Description	Patients receive enzalutamide PO QD. Courses 1-3 repeat every 4 weeks (28 days) and subsequent courses repeat every 12 weeks (84 days) in the absence of disease progression or unacceptable toxicity. Enzalutamide: Given PO Laboratory Biomarker Analysis: Correlative studies
Measure Participants	8
Median (Full Range) [Weeks]	14

3. Secondary Outcome

Title	Progression-free Survival
Description	Kaplan-Meier methodology will be used to estimate event-free curves and corresponding quartiles (including the median).
Time Frame	From first study drug administration to the first occurrence of disease progression or death from any cause, assessed up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Enzalutamide)
Arm/Group Description	Patients receive enzalutamide PO QD. Courses 1-3 repeat every 4 weeks (28 days) and subsequent courses repeat every 12 weeks (84 days) in the absence of disease progression or unacceptable toxicity. Enzalutamide: Given PO Laboratory Biomarker Analysis: Correlative studies
Measure Participants	8
Median (Full Range) [Months]	4.1

4. Secondary Outcome

Title	Overall Survival
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Enzalutamide)
Arm/Group Description	Patients receive enzalutamide PO QD. Courses 1-3 repeat every 4 weeks (28 days) and subsequent courses repeat every 12 weeks (84 days) in the absence of disease progression or unacceptable toxicity. Enzalutamide: Given PO Laboratory Biomarker Analysis: Correlative studies
Measure Participants	8
Count of Participants [Participants]	4 50%

5. Secondary Outcome

Title	Number of Participants With One or More Adverse Events, Measured by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Time Frame	Up to 30 days after study treatment completion, an average of 18 weeks.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Enzalutamide)
Arm/Group Description	Patients receive enzalutamide PO QD. Courses 1-3 repeat every 4 weeks (28 days) and subsequent courses repeat every 12 weeks (84 days) in the absence of disease progression or unacceptable toxicity. Enzalutamide: Given PO Laboratory Biomarker Analysis: Correlative studies
Measure Participants	8
Count of Participants [Participants]	8 100%

6. Secondary Outcome

Title	Disease Control Rate (CR + PR + Stable Disease [SD] > 3 Months)
Description	The count of participants who achieved a CR, PR, or SD for greater than 3 months.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Enzalutamide)
Arm/Group Description	Patients receive enzalutamide PO QD. Courses 1-3 repeat every 4 weeks (28 days) and subsequent courses repeat every 12 weeks (84 days) in the absence of disease progression or unacceptable toxicity. Enzalutamide: Given PO Laboratory Biomarker Analysis: Correlative studies
Measure Participants	8
Count of Participants [Participants]	4 50%

Adverse Events

Time Frame	Adverse Events of Grade 3 and above will be monitored and recorded from the time of the first dose of study treatment through 30 days following the end of study treatment, an average of 18 weeks.
Arm/Group Title	Treatment (Enzalutamide)
Arm/Group Description	Patients receive enzalutamide PO QD. Courses 1-3 repeat every 4 weeks (28 days) and subsequent courses repeat every 12 weeks (84 days) in the absence of disease progression or unacceptable toxicity. Enzalutamide: Given PO Laboratory Biomarker Analysis: Correlative studies
All Cause Mortality
	Treatment (Enzalutamide)
	Affected / at Risk (%)	# Events
Total	4/8 (50%)
Serious Adverse Events
	Treatment (Enzalutamide)
	Affected / at Risk (%)	# Events
Total	1/8 (12.5%)
Blood and lymphatic system disorders
Leukocytosis	1/8 (12.5%)	1
Musculoskeletal and connective tissue disorders
Triple Arthrodesis Right Ankle Surgery	1/8 (12.5%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Enzalutamide)
	Affected / at Risk (%)	# Events
Total	8/8 (100%)
Blood and lymphatic system disorders
Anemia	1/8 (12.5%)	1
Increased white blood cell count	1/8 (12.5%)	1
Eye disorders
Eye Pain	1/8 (12.5%)	1
Gastrointestinal disorders
Abdominal Pain	2/8 (25%)	2
Constipation	2/8 (25%)	2
Dry Mouth	1/8 (12.5%)	1
General disorders
Fatigue	5/8 (62.5%)	5
Ankle Pain	1/8 (12.5%)	3
Genital oder	1/8 (12.5%)	1
Non-cardiac chest pain	1/8 (12.5%)	1
Investigations
Platelet Count Decreased	1/8 (12.5%)	1
Metabolism and nutrition disorders
Hypokalemia	1/8 (12.5%)	1
Anorexia	1/8 (12.5%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/8 (12.5%)	1
Back Pain	1/8 (12.5%)	1
Nervous system disorders
Headache	1/8 (12.5%)	1
Psychiatric disorders
Agitation	2/8 (25%)	3
Insomnia	1/8 (12.5%)	1
Renal and urinary disorders
Decreased Urination	2/8 (25%)	2
Reproductive system and breast disorders
Breast Tenderness	2/8 (25%)	2
Decrease in genital size	1/8 (12.5%)	1
Respiratory, thoracic and mediastinal disorders
Shortness of Breath	2/8 (25%)	4
Skin and subcutaneous tissue disorders
Rash	3/8 (37.5%)	3
Pruritus	2/8 (25%)	2
Alopecia	1/8 (12.5%)	1
Skin Changes	3/8 (37.5%)	3
Paresthesia	1/8 (12.5%)	1
Nail Ridging	1/8 (12.5%)	1
Vascular disorders
Hot Flashes	5/8 (62.5%)	6

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.