SGN-35 in CD30-positive Lymphoproliferative Disorders (ALCL), Mycosis Fungoides (MF), and Extensive Lymphomatoid Papulosis (LyP)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by M.D. Anderson Cancer Center
Sponsor:
Collaborator:
Seattle Genetics, Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01352520
First received: May 10, 2011
Last updated: May 7, 2014
Last verified: May 2014
  Purpose

The goal of this clinical research study is to learn if SGN-35 (brentuximab vedotin) can help to control ALCL, LyP or MF in patients with at least 1 of the 3 skin lymphomas. The safety of the study drug will also be studied.


Condition Intervention Phase
CD-30 Positive Anaplastic Large T-cell Cutaneous Lymphoma
Lymphoma, Primary Cutaneous Anaplastic Large Cell
Lymphomatoid Papulosis
Mycosis Fungoides
Skin Lymphoma
Cutaneous Lymphomas
Lymphoma
Hematologic Disorder
Drug: SGN-35
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Brentuximab Vedotin (SGN-35) at Dose of 1.8 mg/kg IV Every 3 Weeks in Patients With CD30-positive Lymphoproliferative Disorders (Cutaneous Anaplastic Large T-cell Lymphoma (ALCL), Mycosis Fungoides, and Extensive Lymphomatoid Papulosis (LyP)

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Response Rate [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Response rate is percentage of participants with skin lesions that express CD30+ receiving SGN-35 in primary cutaneous ALCL, MF, and extensive lymphomatoid papulosis whose best response during the observation period is a Partial Response (PR), regression of measurable disease, or Complete Response (CR), complete disappearance of all clinical evidence of disease, (i.e. at least moderate improvement). Objective tumor response (PR, CR, PR+CR) based on Response Evaluation Criteria In Solid Tumors (RECIST) criteria.


Estimated Enrollment: 84
Study Start Date: June 2011
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SGN-35
1.8 mg/kg intravenously Day 1 of 21-day cycle.
Drug: SGN-35
1.8 mg/kg administered by outpatient IV infusion given over approximately 30 minutes on Day 1 of each 21-day cycle.
Other Name: Brentuximab vedotin

  Hide Detailed Description

Detailed Description:

The Study Drug:

Brentuximab vedotin is an antibody that is designed to find a certain protein (called CD30) on cancer cells and bind to it. It is designed to then enter the cell and release a molecule that may kill the cancer cells.

Study Drug Administration:

If you are found eligible to take part in this study, you will begin receiving brentuximab vedotin by vein over 30 minutes on Day 1 of each 21-day study cycle. If you have side effects after your first dose and your doctor thinks it is in your best interest, future doses may be lowered or delayed for up to 3 weeks.

Premedications:

If you have any reactions at the infusion site after you receive the study drug during Cycle 1, you may be given acetaminophen (Tylenol) or diphenhydramine (Benadryl) 30-60 minutes before all following infusions.

Study Visits:

At each clinic visit, including follow-up visits (described below), you will have full skin exams. You will be checked to see how much of your skin's surface has lesions. Up to 6 skin lesions will be selected to be photographed and measured at each visit. Your private areas will be covered (as much as possible), and a picture of your face will not be taken unless there are lesions on your face. You will not be able to be identified in the photographs. The following tests and procedures will also be performed:

On Day 1 of all study cycles (before you receive the study drug):

  • You will have a physical exam.
  • Your performance status will be recorded.
  • You will be asked about any drugs that you may be taking and if you are having any side effects.
  • You will fill out the 3 quality-of-life questionnaires.
  • Blood (about 4-6 teaspoons) will be drawn for routine tests and to check the status of the disease.
  • If you have not had a lesion biopsy within the last 6 weeks you will have a lesion biopsy to check the status of the disease and for PGx testing.

Length of Study Treatment:

You may receive the study drug for up to 8 cycles. You will be taken off study if the disease gets worse or intolerable side effects occur.

If the disease has a complete response, you may receive the study drug for 2 more cycles if the study doctor thinks it is in your best interest.

If the disease has complete response, then comes back, you may receive the study drug for 8 more cycles if the doctor thinks it is in your best interest.

If you are doing better at the end of 8 cycles but the disease is not in complete remission, the study doctor may allow you to receive the study drug every 3 weeks at the full dose or every 2 weeks at a lower dose for 8 additional cycles. If you continue to have improvement after these 16 cycles, the study doctor may allow you to continue receiving the study drug. The study doctor will discuss this with you.

Follow-up Visits:

About 3-4 weeks after you have stopped taking the study drug, the following tests and procedures will be performed:

  • Your medical history will be recorded.
  • Your performance status will be recorded.
  • You will have a physical exam.
  • You will be asked if you are having any side effects.
  • You will fill out the 3 quality-of-life questionnaires.
  • Blood (about 4-6 teaspoons) will be drawn for routine tests and to check the status of the disease.
  • You will have a CT or PET scan to check the status of the disease.
  • You will have a lesion biopsy to check the status of the disease and for PGx testing.

You will then have follow-up evaluations every 12-16 weeks until the study is no longer open:

  • You will have a physical exam.
  • You will be asked about any side effects you may be having.
  • Your medical history will be recorded.

Long-term Follow-up:

You or your primary doctor may be contacted for long-term follow-up on the status of the disease, any study-related nerve damage (including loss of motor or sensory function) you have, and your overall health status, until the study closes.

This is an investigational study. Brentuximab vedotin is not FDA approved or commercially available for use in patients with ALCL, LyP or MF. It is currently being used for research purposes only.

Up to 84 patients will take part in this study. All will be enrolled at MD Anderson.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must have a biopsy confirmed diagnosis based on a combination of histological and clinical criteria of CD30+ lymphomatoid papulosis, CD30+ primary cutaneous anaplastic large T-cell lymphoma (pc-ALCL), or CD30+ mycosis fungoides for the phase II trial. There is no specific limit or validated amount other than positive cells on 1HC cells in tumor cells.
  2. Patients with pc-ALCL that has spread systemically (e.g. to lymph nodes, bone marrow or visceral organs) may be included so long as pc-ALCL was the primary diagnosis for at least 6 months before systemic involvement was confirmed. MF patients must be stage IB or greater.
  3. Systemic involvement (i.e., nodal, bone marrow or visceral organ involvement) will be evaluated by CT and/or PET and bone marrow biopsy(if indicated on patients with blood involvement) in patients with pc-ALCL or MF at baseline.
  4. Patients' biopsies must be histologically confirmed CD30 positive within 36 months of enrollment.
  5. pc-ALCL and MF patients must have progressed or relapsed after treatment with local radiation therapy, phototherapy, topical chemotherapy, or have failed systemic therapy of at least one single agent (e.g., methotrexate or bexarotene or other non-CD30 antibody) or one multi-agent chemotherapy (e.g. CHOP: cyclophosphamide, doxorubicin, vincristine, and prednisone). pc-ALCL classified patients are required to have one or more cutaneous tumors that by history have been present for at least 3 months.
  6. All patients must be considered an eligible candidate for systemic therapy as determined by the investigator. To be eligible, LYP patients must be in need of systemic therapy ie have scarring or active lesions (>/=10 per month), or any number of active lesions on face, hands or feet.
  7. Patients must have the following minimum wash-out from previous treatments: a. >/= 4 weeks for local radiation therapy, systemic cytotoxic anticancer therapy, treatment with other anticancer investigational agents. b. > 2 weeks for oral methotrexate, retinoids or biological response modifiers therapy for any indication, or topical prescription or topical therapy. c. >/= 12 weeks for any immunotherapy (e.g., monoclonal antibody). Patients with rapidly progressive disease may be treated earlier than the required washout period; patients should have recovered from prior treatment-related toxicities
  8. Patients must have an ECOG performance status of </= 2.
  9. Patients must be at least 18 years of age.
  10. Patients must be available for periodic blood sampling, study-related assessments, and management of toxicity at the treating institution.
  11. Females of childbearing potential [a female not post menopausal for at least 12 months or not surgically sterilized] must have a negative beta-HCG pregnancy </=7 days prior to Day 1 of Cycle 1. If the pregnancy test is outside institutional normal range at pretreatment, the subject must have a second pregnancy test. If the second pregnancy test is outside institutional normal range then a gynecology consult is needed to confirm the subject is not pregnant. All patients must agree to use an effective contraceptive method during the course of the study.
  12. Patients must give written informed consent. A copy of the signed informed consent form will be retained in the patient's chart.
  13. The following required baseline laboratory data: absolute neutrophil count (ANC) >/= 1000/microliter, platelets >/= 50,000/µL (unless documented bone marrow involvement with lymphoma), bilirubin </= 1.5X upper limit of normal (ULN) or </= 3X ULN for patients with Gilbert's disease, serum creatinine </= 1.5X ULN, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) </= 2.5X ULN.

Exclusion Criteria:

  1. Concomitant corticosteroid use for systemic or topical treatment of skin disease is not allowed except a dose of steroid of no more than 20 mg of prednisone or its equivalence is allowed of asthma, COPD or IBD .Stable use of topical corticosteroids of mid-potency will be allowed for patients with erythroderma-Sezary syndrome (T4) and tumor stage (T3) with intense pruritus.
  2. Patients with known grade 3 or higher (per CTCAE v.4.0 criteria) active systemic or cutaneous viral, bacterial or fungal infection.
  3. Patients who are known to be HIV, Hepatitis B, or Hepatitis C positive.
  4. Patients with known hypersensitivity to recombinant proteins or any excipient contained in the drug formulation that includes trehalose, sodium citrate, and polysorbate 80.
  5. Patient with a history of other malignancies during the past three years. (The following are exempt from the 3-year limit: non-melanoma skin cancer, melanoma in situ, curatively treated localized prostate cancer, and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on PAP smear.)
  6. Patients with congestive heart failure, Class III or IV, by the NYHA criteria.
  7. Patients who are pregnant or breastfeeding.
  8. Patients with any serious underlying medical condition that would impair their ability to receive or tolerate the planned treatment.
  9. Patients with dementia or altered mental status that would preclude understanding and rendering of informed consent.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01352520

Contacts
Contact: Madeleine Duvic, MD 713-792-4578

Locations
United States, Texas
UT MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Madeleine Duvic, MD         
Sponsors and Collaborators
M.D. Anderson Cancer Center
Seattle Genetics, Inc.
Investigators
Study Chair: Madeleine Duvic, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01352520     History of Changes
Other Study ID Numbers: 2010-0914, NCI-2011-01045
Study First Received: May 10, 2011
Last Updated: May 7, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
systemic therapy
cutaneous anaplastic large T cell lymphoma
ALCL
lymphomatoid papulosis
LyP
mycosis fungoides
MF
SGN-35 (brentuximab vedotin)
skin lymphomas
CD30-positive lymphoproliferative disorders
tumor lymphocytes
cutaneous lymphomas
CD30+ expression
Hematologic Disorder
Lymphoma

Additional relevant MeSH terms:
Hematologic Diseases
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Mycoses
Mycosis Fungoides
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Lymphomatoid Papulosis
Lymphoma, Primary Cutaneous Anaplastic Large Cell
Neoplasms by Histologic Type
Neoplasms
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 26, 2014