Brentuximab Vedotin (SGN-35) in Patients With Mycosis Fungoides With Variable CD30 Expression Level

• Sponsor: Youn Kim (Other)
• Overall Status: Completed
• CT.gov ID: NCT01396070
• Collaborator: Seagen Inc. (Industry)
• Enrollment: 36
• Location: 1
• Arm: 1
• Duration (Months): 60
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The purpose of this study is to learn the effects of brentuximab vedotin (SGN-35), an investigational medication, on patients with cutaneous T cell lymphoma (CTCL), specifically mycosis fungoides (MF) and Sezary syndrome (SS). Despite a wide range of therapeutic options, the treatments are associated with short response duration, thus this condition is largely incurable. This investigational drug may offer less toxicity than standard treatments and have better tumor specific targeting.

Condition or Disease	Intervention/Treatment	Phase
Non-Hodgkin Lymphoma (NHL); Cutaneous Lymphoma; Cutaneous T-cell Lymphoma (CTCL); Mycosis Fungoides; Sezary Syndrome	Drug: Brentuximab vedotin	Phase 2

Detailed Description

This phase 2 exploratory study will evaluate the clinical response of brentuximab vedotin in MF and SS, where tumor cells express variable levels of CD30 target molecule.

The primary objective is to explore the biologic activity of brentuximab vedotin in patients with MF and SS, the most common types of cutaneous T-cell lymphoma (CTCL), where expression of CD30 is variable. Brentuximab vedotin has significant biologic activity in Hodgkin's disease (HD) where only a small numbers of CD30 positive tumor cells are present, as well as in lymphomas with large numbers of CD30-expressing tumor cells such as systemic anaplastic large cell lymphoma (sALCL). The subject grouping by CD30 expression levels (low, intermediate, high) is for accrual purposes only, to ensure that a wide range of CD30 expression is studied.

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Exploratory Pilot Study of Brentuximab Vedotin (SGN-35) in Patients With Mycosis Fungoides and Sézary Syndrome With Variable CD30 Expression Level
• Study Start Date: May 1, 2011
• Actual Primary Completion Date: Apr 1, 2015
• Actual Study Completion Date: May 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Brentuximab vedotin Novel antibody-drug conjugate, 1.8 mg/kg intravenously every 3 weeks	Drug: Brentuximab vedotin; 1.8 mg/kg by IV every 3 weeks for a maximum of 16 doses (8 cycles). Brentuximab vedotin is an antibody conjugate, consisting of the chimeric IgG1 anti-CD30 antibody cAC10; the microtubule disrupting agent monomethyl auristatin E (MMAE); a protease-cleavable linker that covalently attaches MMAE to cAC10.; Other Names: Adcetris SGN-35

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate (ORR) [2 years]

   Overall response rate of brentuximab vedotin in this study population.

Secondary Outcome Measures

1. Overall Stable Disease Rate [2 years]

   Overall Stable Disease Rate (SD) in this study population. 3 subjects were not evaluable.

2. Overall Partial Response Rate [2 years]

   Overall Partial Response Rate (PR) in this study population. 3 subjects were not evaluable.

3. Overall Non-Evaluable Response [4 weeks]

   Overall Non-Evaluable Response of full patient population 3 subjects were not evaluable.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Biopsy-proven MF/SS, stage IB-IVB, and failed one standard systemic therapy. Skin biopsy must be within 3 months of beginning study medication

• At least the following wash-out from prior treatments:

• ≥ 3 weeks for local radiation therapy, systemic cytotoxic anticancer therapy, treatment with other anti-cancer investigational agents (including monoclonal antibody)

• 3 weeks for retinoids, interferons, vorinostat, romidepsin, denileukin diftitox and phototherapy

• 2 wks for topical therapy (including topical steroid, retinoid, nitrogen mustard, or imiquimod)

• At least 18 years of age

• ECOG performance status of ≤ 2

• Must be able to commit to study schedule

• Absolute neutrophil count (ANC) ≥ 1000/uL

• Platelets ≥ 50,000/uL

• Bilirubin ≤ 2X upper limit of normal (ULN) (EXCEPTION: Gilbert's disease ≤ 3X ULN)

• Serum creatinine ≤ 2X ULN

• Alanine aminotransferase (ALT) ≤ 3X ULN

• Aspartate aminotransferase (AST) ≤ 3X ULN

• Negative serum beta-HCG pregnancy test result within 7 days of first treatment, if a woman of childbearing potential

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Mycosis fungoides (MF) with limited disease (stage IA) or central nervous system (CNS) disease

• Systemic or topical concomitant corticosteroid use for treatment of skin disease (EXCEPTION: Oral prednisone allowed at ≤ 10 mg/day)

• Known Grade 3 or higher (per NCI CTCAE v4.0 criteria) active systemic or cutaneous viral, bacterial, or fungal infection

• Known to be Hepatitis B or Hepatitis C antibody positive

• HIV-positive with have a measurable viral load while on antiretroviral medication

• Known hypersensitivity to recombinant proteins or any excipient contained in the drug formulation.

• History of other malignancies during the past 3 years (EXCEPTIONS: non-melanoma skin cancer; curatively treated localized prostate cancer; curatively treated localized breast cancer; resected thyroid cancer; cervical intraepithelial neoplasia; or cervical carcinoma in situ on biopsy).

• Pregnant

• Breastfeeding

• Congestive heart failure, Class III or IV, by New York Heart Association (NYHA) criteria.

• Any serious underlying medical condition that would impair subject's ability to receive or tolerate the planned treatment.

• Dementia or altered mental status that would preclude subject's understanding and rendering of informed consent.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University School of Medicine	Stanford	California	United States	94305

Sponsors and Collaborators

• Youn Kim
• Seagen Inc.

Investigators

• Principal Investigator: Youn H Kim, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Youn Kim, The Joanne and Peter Haas, Jr, Professor for Cutaneous Lymphoma Research, Stanford University
• ClinicalTrials.gov Identifier: NCT01396070
• Other Study ID Numbers: IRB-21324; LYMNHL0089; SU-06212011-7946
• First Posted: Jul 18, 2011
• Last Update Posted: Apr 5, 2017
• Last Verified: Feb 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Mycoses; Lymphoma; Lymphoma, Non-Hodgkin; Mycosis Fungoides; Sezary Syndrome; Lymphoma, T-Cell, Cutaneous; Brentuximab Vedotin

Study Results

Participant Flow

Arm/Group Title	Brentuximab Vedotin
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg intravenously (IV) once every 3 weeks (1 cycle)
Period Title: Overall Study
STARTED	36
COMPLETED	17
NOT COMPLETED	19

Baseline Characteristics

Arm/Group Title	Brentuximab Vedotin
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg intravenously (IV) once every 3 weeks (1 cycle)
Overall Participants	36
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	18 50%
>=65 years	18 50%
Sex: Female, Male (Count of Participants)
Female	11 30.6%
Male	25 69.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 5.6%
Not Hispanic or Latino	33 91.7%
Unknown or Not Reported	1 2.8%
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	7 19.4%
White	25 69.4%
More than one race	0 0%
Unknown or Not Reported	4 11.1%
CD30 grouping at screening (participants) [Number]
< 10% CD30 positivity	17 47.2%
10% to 50% CD30 positivity	15 41.7%
> 50% CD30 positivity	4 11.1%
Clinical Stage (Count of Participants)
Stage IB	6 16.7%
Stage IIB	16 44.4%
Stage IV/SS (includes IVA, IVA/SS and III)	14 38.9%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate (ORR)
Description	Overall response rate of brentuximab vedotin in this study population.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

The percentage was calculated by adding Complete response (CR) + Partial Response (PR) = Overall rate. 3 subjects were not evaluable.

Arm/Group Title	Overall Response Rate (%)
Arm/Group Description	Overall Response Rate of all patients
Measure Participants	33
Everyone evaluable (ORR)	70
Tissue CD30 Expression Group A	56
Tissue CD30 Expression Group B	79
Tissue CD30 Expression Group C	100
Stage IB	83
Stage IIB	94
Stage IV/SS	63
Females	30
Males	69

2. Secondary Outcome

Title	Overall Stable Disease Rate
Description	Overall Stable Disease Rate (SD) in this study population. 3 subjects were not evaluable.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Brentuximab Vedotin
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg intravenously (IV) once every 3 weeks (1 cycle)
Measure Participants	33
Count of Participants [Participants]	5 13.9%

3. Secondary Outcome

Title	Overall Partial Response Rate
Description	Overall Partial Response Rate (PR) in this study population. 3 subjects were not evaluable.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Brentuximab Vedotin
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg intravenously (IV) once every 3 weeks (1 cycle)
Measure Participants	33
Count of Participants [Participants]	21 58.3%

4. Secondary Outcome

Title	Overall Non-Evaluable Response
Description	Overall Non-Evaluable Response of full patient population 3 subjects were not evaluable.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Brentuximab Vedotin
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg intravenously (IV) once every 3 weeks (1 cycle)
Measure Participants	33
Count of Participants [Participants]	4 11.1%

Adverse Events

Time Frame	4 weeks
Arm/Group Title	All Participants
Arm/Group Description	All reported AE's on trial
All Cause Mortality
	All Participants
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	All Participants
	Affected / at Risk (%)	# Events
Total	23/36 (63.9%)
Blood and lymphatic system disorders
Blood disorder	2/36 (5.6%)	5
Febrile Neutropenia	2/36 (5.6%)	2
Hypercalcemia	1/36 (2.8%)	2
Thrombocytopenia	1/36 (2.8%)	4
White blood cell decreased	1/36 (2.8%)	1
Hypomagnesemia	1/36 (2.8%)	1
Gastrointestinal disorders
Diarrhea	3/36 (8.3%)	3
GVHD	1/36 (2.8%)	1
Acute kidney Injury	1/36 (2.8%)	2
Nausea	1/36 (2.8%)	1
Vomitting	1/36 (2.8%)	1
Infections and infestations
Sepsis	2/36 (5.6%)	2
Skin Infection	2/36 (5.6%)	2
Musculoskeletal and connective tissue disorders
Infection and Pain of skin	1/36 (2.8%)	2
Psychiatric disorders
Confusion	1/36 (2.8%)	1
Reproductive system and breast disorders
Pneumonia	1/36 (2.8%)	1
Respiratory, thoracic and mediastinal disorders
Respiratory failure	1/36 (2.8%)	1
Other (Not Including Serious) Adverse Events
	All Participants
	Affected / at Risk (%)	# Events
Total	32/36 (88.9%)
Blood and lymphatic system disorders
Aberrant T-cell population (blood)	2/36 (5.6%)	2
Dysphonia	2/36 (5.6%)	2
Hyponatremia	2/36 (5.6%)	2
Gastrointestinal disorders
Dyspepsia	3/36 (8.3%)	3
General disorders
Infusion Reaction	2/36 (5.6%)	2
Lower extremity edema	2/36 (5.6%)	2
Pain	2/36 (5.6%)	2
Investigations
Leukopenia	2/36 (5.6%)	2
LFTs elevated	2/36 (5.6%)	2
Musculoskeletal and connective tissue disorders
Myalgias	2/36 (5.6%)	2
Nervous system disorders
Peripheral Neuropathy	2/36 (5.6%)	2
Respiratory, thoracic and mediastinal disorders
Cough	2/36 (5.6%)	2
Skin and subcutaneous tissue disorders
Skin eruption	4/36 (11.1%)	4
Social circumstances
Weight Loss	3/36 (8.3%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.