Cutaneous Lymphoma, Cutaneous T-cell Lymphoma (CTCL), Mycosis Fungoides, Non-Hodgkin Lymphoma (NHL), Sezary Syndrome
Conditions
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.
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.
Interventions
DRUGBrentuximab 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.
Sponsors
Seagen Inc.
Youn Kim
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | 2 years | Overall response rate of brentuximab vedotin in this study population. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Stable Disease Rate | 2 years | Overall Stable Disease Rate (SD) in this study population. 3 subjects were not evaluable. |
| Overall Partial Response Rate | 2 years | Overall Partial Response Rate (PR) in this study population. 3 subjects were not evaluable. |
| Overall Non-Evaluable Response | 4 weeks | Overall Non-Evaluable Response of full patient population 3 subjects were not evaluable. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Brentuximab Vedotin Brentuximab vedotin 1.8 mg/kg intravenously (IV) once every 3 weeks (1 cycle) | 36 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 8 |
| Overall Study | Death | 2 |
| Overall Study | Lack of Efficacy | 4 |
| Overall Study | Physician Decision | 3 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Brentuximab Vedotin |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 18 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants |
| CD30 grouping at screening < 10% CD30 positivity | 17 participants |
| CD30 grouping at screening 10% to 50% CD30 positivity | 15 participants |
| CD30 grouping at screening > 50% CD30 positivity | 4 participants |
| Clinical Stage Stage IB | 6 Participants |
| Clinical Stage Stage IIB | 16 Participants |
| Clinical Stage Stage IV/SS (includes IVA, IVA/SS and III) | 14 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 33 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 25 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 32 / 36 |
| serious Total, serious adverse events | 23 / 36 |
Outcome results
Primary
Overall Response Rate (ORR)
Overall response rate of brentuximab vedotin in this study population.
Time frame: 2 years
Population: The percentage was calculated by adding Complete response (CR) + Partial Response (PR) = Overall rate. 3 subjects were not evaluable.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Overall Response Rate (%) | Overall Response Rate (ORR) | Everyone evaluable (ORR) | 70 percentage |
| Overall Response Rate (%) | Overall Response Rate (ORR) | Females | 30 percentage |
| Overall Response Rate (%) | Overall Response Rate (ORR) | Males | 69 percentage |
| Overall Response Rate (%) | Overall Response Rate (ORR) | Tissue CD30 Expression Group A | 56 percentage |
| Overall Response Rate (%) | Overall Response Rate (ORR) | Tissue CD30 Expression Group B | 79 percentage |
| Overall Response Rate (%) | Overall Response Rate (ORR) | Tissue CD30 Expression Group C | 100 percentage |
| Overall Response Rate (%) | Overall Response Rate (ORR) | Stage IB | 83 percentage |
| Overall Response Rate (%) | Overall Response Rate (ORR) | Stage IIB | 94 percentage |
| Overall Response Rate (%) | Overall Response Rate (ORR) | Stage IV/SS | 63 percentage |
Secondary
Overall Non-Evaluable Response
Overall Non-Evaluable Response of full patient population 3 subjects were not evaluable.
Time frame: 4 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Overall Response Rate (%) | Overall Non-Evaluable Response | 4 Participants |
Secondary
Overall Partial Response Rate
Overall Partial Response Rate (PR) in this study population. 3 subjects were not evaluable.
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Overall Response Rate (%) | Overall Partial Response Rate | 21 Participants |
Secondary
Overall Stable Disease Rate
Overall Stable Disease Rate (SD) in this study population. 3 subjects were not evaluable.
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Overall Response Rate (%) | Overall Stable Disease Rate | 5 Participants |