ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety and Effectiveness of A-dmDT390-bisFv(UCHT1) Fusion Protein in Subjects With Mycosis Fungoides (Resimmune®)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02943642
Recruitment Status : Not yet recruiting
First Posted : October 25, 2016
Last Update Posted : October 25, 2016
Sponsor:
Collaborators:
City of Hope National Medical Center
Columbia University
Dana-Farber Cancer Institute
Feinberg School of Medicine, Northwestern University
H. Lee Moffitt Cancer Center and Research Institute
Ohio State University Comprehensive Cancer Center
Rush University Medical Center
Scott and White Hospital & Clinic
Yale University
Stanford University
Thomas Jefferson University
University of Arkansas
University of Colorado Denver School of Medicine Barbara Davis Center
University of Texas Southwestern Medical Center
University of Washington
Vanderbilt University School of Medicine
Washington University School of Medicine
Information provided by (Responsible Party):
Angimmune LLC

Brief Summary:
This study evaluates the effectiveness — as judged by complete response — of a single four-day treatment with the fusion protein A-dmDT390-bisFv(UCHT1) compared to oral Zolinza (Vorinostat), in a randomized 2-arm trial after a maximum of 12 months of treatment. Patient eligibility is stage IB/IIB mycosis fungoides with mSWAT < 50 who have never had lymphoid disease or a prior bone marrow / HSCT transplant.

Condition or disease Intervention/treatment Phase
Mycosis Fungoides Biological: A-dmDT390-bisFv(UCHT1) Drug: Vorinostat Phase 2

Detailed Description:

Primary Objective: This study objective is to document the incidence of complete responses compared to oral vorinostat, in a randomized 2-arm trial after a maximum of 12 months of treatment for subjects with stage IB/IIB mycosis fungoides with mSWAT < 50 who have never had lymphoid disease or a prior bone marrow / HSCT transplant.

Secondary Objective: To further explore the toxicity profile of A-dmDT390-bisFv(UCHT1) fusion protein for subjects with mycosis fungoides who have been selected to be free from preexisting cardiac disease and never treated with Campath.

Number of Subjects: Lead-in Dosing: 12 / Randomized: 162

Patients will receive full supportive care during the course of the study. Participation in the study will require IV infusions of the research agent 2 times a day for four days (protocol FDA outpatient approved), as well as frequent outpatient blood draws for the first 30 days. Patients with partial or complete remissions at their 1 month follow up visit will have another follow-up visit on day 60, then every three months for 1 year, followed by annual visits to assess duration of the response.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 162 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety and Effectiveness of A-dmDT390-bisFv(UCHT1) Fusion Protein (Resimmune®) in Subjects With Mycosis Fungoides: A Phase II Multi-center Randomized Clinical Trial
Study Start Date : January 2017
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : May 2020


Arm Intervention/treatment
Experimental: A-dmDT390-bisFv(UCHT1)
A-dmDT390-bisFv(UCHT1) will be administered as Total Dose µg/kg given as 1/8 Total Dose µg/kg/injection twice a day 4-6 hours apart for four consecutive days (days 1-4) into a free flowing IV over a period of approximately 15 minutes.
Biological: A-dmDT390-bisFv(UCHT1)
anti-T cell immunotoxin (antibody targeting CD3 on T-cells tagged with diphtheria toxin without binding domain)
Other Name: Resimmune® (proposed marketing designation)

Active Comparator: Vorinostat
Subjects in the control arm will receive oral vorinostat capsules at a dose of 400 mg daily up to 12 months in duration until disease progression or uncontrolled side effects take place. Subjects in the vorinostat arm who experience progressive disease may cross over into the experimental arm after 6 months of treatment after a 2-week vorinostat washout period.
Drug: Vorinostat
ZOLINZA is a histone deacetylase (HDAC) inhibitor indicated for the treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma (CTCL) who have progressive, persistent or recurrent disease on or following two systemic therapies.
Other Name: Zolinza

Experimental: Lead-in Dosing single arm

Dose Group 1: A-dmDT390-bisFv(UCHT1) will be administered as 5 µg/kg given as 0.625 µg/kg/injection twice a day 4-6 hours apart for four consecutive days (days 1-4) into a free flowing IV over a period of approximately 15 minutes.

Dose Group 2: A-dmDT390-bisFv(UCHT1) will be administered as 10 µg/kg given as 1.25 µg/kg/injection twice a day 4-6 hours apart for four consecutive days (days 1-4) into a free flowing IV over a period of approximately 15 minutes.

Biological: A-dmDT390-bisFv(UCHT1)
anti-T cell immunotoxin (antibody targeting CD3 on T-cells tagged with diphtheria toxin without binding domain)
Other Name: Resimmune® (proposed marketing designation)




Primary Outcome Measures :
  1. Incidence of Complete Responses (CR) [ Time Frame: Skin lesions will be judged for mSWAT scores for judging the duration of response at 12 months in the experimental arm and 6 months in the comparator arm. ]

    Evaluation of Target Lesions

    Complete Response (CR) in mycosis fungoides: (a) Cutaneous lesions consisting of erythematous patches and plaques and erythroderma must be absent giving an mSWAT of 0 that persists for at least 30 days, and (b) the spleen and liver should be normal sized by physical exam. Subjects in the experimental arm who have a CR at 12 months will be encouraged to enter the Part B followup that consists of a a yearly physical exam from year 2 to year to year 6 and skin assessment as long as the CR is maintained.

    Partial Response (PR) in mycosis fungoides: (a) There must be a reduction of 50% in cutaneous lesions as judged by mSWAT and (b) no new evidence of disease or disease progression of skin lesions.

    Progressive Disease (PD): At least a 25% increase in the mSWAT score from its nadir value.

    Treatment Failure: Failure to achieve a PR or CR: Relapse/Progression: Relapse is defined at reevaluation as no longer a CR or PR.



Secondary Outcome Measures :
  1. Progression Free Survival [ Time Frame: 12 months ]
    Determine the Progression Free Survival duration, PFS

  2. Median duration of Complete Response [ Time Frame: 12 months ]
    Determine the Median duration of CR for each arm.


Other Outcome Measures:
  1. Primary Toxicity profile [ Time Frame: 3 months ]

    Determine the Primary Toxicity profile for treatment of A-dmDT390-bisFv(UCHT1). Toxicities from the previous phase I clinical trial known to be associated with A-dmDT390-bisFv(UCHT1) include:

    • Frequent: elevated AST, ALT and CPK; hypersensitivity reactions such as rigors and chills during infusions, hypoalbuminemia.
    • Rare: Vascular leak syndrome.
    • Hypersensitivity infusion reaction.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects must have signed the current IRB approved informed consent prior to registration (see Informed Consent).
  • Mycosis fungoides, confirmed by biopsy or flow cytometry, without large cell transformation.
  • Relapse or progression after 2 or more systemic therapies. Note: Total electron beam therapy can be counted as a systemic therapy.
  • Disease stage as follows:

    • Stage IB with no lymph node involvement including lymphadenopathy with mSWAT <50;
    • Stage IIB with no lymph node involvement including lymphadenopathy with mSWAT <50.
  • Age 18 years.
  • Subjects must have a performance status of < 2 on Eastern Cooperative Oncology Group scale (see Appendix A).
  • Subjects must have normal lung function evaluated by pulse oximetry with O2 saturation values between 95-100%.
  • Subjects must have fully recovered from toxicity of prior chemotherapy or radiation therapy.
  • Subjects must have:

    • bilirubin < 1.5 mg/dL,
    • transaminases < 2.5 X ULN,
    • albumin > 3 gm/dL,
    • creatinine < 2.0 mg/dL.
    • Subjects who have had albumin < 3 gm/dL boosted by an albumin infusion must be observed to maintain albumin at > 3gm dL for 14 days without an additional infusion.
  • Subjects must have a normal echocardiogram (EF > 50% normal) without any evidence of cardiac chamber hypertrophy, dilatation or hypokinesis.
  • Females and males must be willing to use an approved form of birth control while on this study and for 2 weeks after completion.
  • Subjects must have a pretreatment anti-DT titer of 20 μg/ml or less. Subjects with titers between 21 and 35 μg/ml will have an additional anti-DT neutralization test using subject's serum and A-dmDT390-bisFv(UCHT1). If neutralization is not found these titers will be considered acceptable.

Exclusion Criteria:

  • Failure to meet any of the criteria.
  • Inability to give informed consent because of psychiatric problems, or complicated medical problems.
  • Allergic to diphtheria toxin a component of the study drug A-dmDT390-bisFv(UCHT1).
  • Serious concurrent medical problems, uncontrolled infections, or disseminated intravascular coagulopathy (DIC), hepatic cirrhosis, or chronic kidney disease.
  • CNS leukemia.
  • Preexisting cardiovascular disease. The only exception being well controlled essential hypertension with a sitting blood pressure (B.P.) of <160 systolic and <90 diastolic without any evidence of structural heart disease or one episode of myocardial infarction > 8 months ago. Subjects receiving a beta-blocker for hypertension should be converted to another antihypertensive drug class 2-3 weeks before receiving the study drug to prevent a drug-drug interaction reactive tachycardia. Angiotensin inhibitors, angiotensin receptor blockers and calcium channel blockers are all acceptable. A past history of any of the following conditions is considered as exclusions to study participation:

    • Congestive heart failure,
    • Atrial fibrillation,
    • Pulmonary hypertension,
    • Anticoagulant drug therapy,
    • Thromboembolic events,
    • Cardiomyopathy or a myocardial infarction within the past 8 months. The PI and the Clinical Coordinator will be asked to verify that their referred subjects do not have these exclusionary histories listed in 3.2 and a copy of this verification must be sent to the Sponsor before the Sponsor will approve of enrollment. Referring physicians will not need to sign.
  • Pregnant or nursing women will be excluded from study.
  • History of cirrhosis of the liver based on the Child-Pugh score of Class B or C are not eligible to participate.
  • Prior treatment with alemtuzumab (Campath) or similar agents or procedures that depress blood T cell counts to below 50% of the lower limit of normal.
  • Prior history of bone marrow transplant or HSCT is an exclusion.
  • Prior treatment with vorinostat (Prior treatment with vorinostat for lead-in dosing arm is acceptable).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02943642


Contacts
Contact: Paul H Neville 5083978150 pauln@angimmune.com

Sponsors and Collaborators
Angimmune LLC
City of Hope National Medical Center
Columbia University
Dana-Farber Cancer Institute
Feinberg School of Medicine, Northwestern University
H. Lee Moffitt Cancer Center and Research Institute
Ohio State University Comprehensive Cancer Center
Rush University Medical Center
Scott and White Hospital & Clinic
Yale University
Stanford University
Thomas Jefferson University
University of Arkansas
University of Colorado Denver School of Medicine Barbara Davis Center
University of Texas Southwestern Medical Center
University of Washington
Vanderbilt University School of Medicine
Washington University School of Medicine

Publications of Results:
Responsible Party: Angimmune LLC
ClinicalTrials.gov Identifier: NCT02943642     History of Changes
Other Study ID Numbers: FDA IND 100712 Phase II
First Posted: October 25, 2016    Key Record Dates
Last Update Posted: October 25, 2016
Last Verified: October 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Angimmune LLC:
MF
CTCL
Cutaneous T Cell Lymphoma

Additional relevant MeSH terms:
Mycoses
Mycosis Fungoides
Lymphoma, T-Cell, Cutaneous
Lymphoma, T-Cell
Lymphoma, Non-Hodgkin
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Vorinostat
Antineoplastic Agents
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action