Safety and Effectiveness of A-dmDT390-bisFv(UCHT1) Fusion Protein in Subjects With Mycosis Fungoides
NCT ID: NCT02943642
Last Updated: 2016-10-25
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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UNKNOWN
PHASE2
162 participants
INTERVENTIONAL
2017-01-31
2020-05-31
Brief Summary
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Detailed Description
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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.
Conditions
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Keywords
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Study Design
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RANDOMIZED
CROSSOVER
TREATMENT
NONE
Study Groups
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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.
A-dmDT390-bisFv(UCHT1)
anti-T cell immunotoxin (antibody targeting CD3 on T-cells tagged with diphtheria toxin without binding domain)
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.
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.
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.
A-dmDT390-bisFv(UCHT1)
anti-T cell immunotoxin (antibody targeting CD3 on T-cells tagged with diphtheria toxin without binding domain)
Interventions
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A-dmDT390-bisFv(UCHT1)
anti-T cell immunotoxin (antibody targeting CD3 on T-cells tagged with diphtheria toxin without binding domain)
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 Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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).
18 Years
ALL
No
Sponsors
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City of Hope National Medical Center
OTHER
Columbia University
OTHER
Dana-Farber Cancer Institute
OTHER
Northwestern University Feinberg School of Medicine
OTHER
H. Lee Moffitt Cancer Center and Research Institute
OTHER
Ohio State University Comprehensive Cancer Center
OTHER
Rush University Medical Center
OTHER
Scott and White Hospital & Clinic
OTHER
Yale University
OTHER
Stanford University
OTHER
Thomas Jefferson University
OTHER
University of Arkansas
OTHER
University of Colorado, Denver
OTHER
University of Texas Southwestern Medical Center
OTHER
University of Washington
OTHER
Vanderbilt University School of Medicine
OTHER
Washington University School of Medicine
OTHER
Angimmune LLC
INDUSTRY
Responsible Party
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Central Contacts
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References
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Frankel AE, Woo JH, Ahn C, Foss FM, Duvic M, Neville PH, Neville DM. Resimmune, an anti-CD3epsilon recombinant immunotoxin, induces durable remissions in patients with cutaneous T-cell lymphoma. Haematologica. 2015 Jun;100(6):794-800. doi: 10.3324/haematol.2015.123711. Epub 2015 Mar 20.
Valipour A, Jager M, Wu P, Schmitt J, Bunch C, Weberschock T. Interventions for mycosis fungoides. Cochrane Database Syst Rev. 2020 Jul 7;7(7):CD008946. doi: 10.1002/14651858.CD008946.pub3.
Other Identifiers
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FDA IND 100712 Phase II
Identifier Type: -
Identifier Source: org_study_id