Safety and Effectiveness of A-dmDT390-bisFv(UCHT1) Fusion Protein in Subjects With Mycosis Fungoides
Resimmune®
1 other identifier
interventional
162
0 countries
N/A
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jan 2017
Typical duration for phase_2
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 18, 2016
CompletedFirst Posted
Study publicly available on registry
October 25, 2016
CompletedStudy Start
First participant enrolled
January 1, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2020
CompletedOctober 25, 2016
October 1, 2016
1.9 years
October 18, 2016
October 21, 2016
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Incidence of Complete Responses (CR)
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.
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.
Secondary Outcomes (2)
Progression Free Survival
12 months
Median duration of Complete Response
12 months
Other Outcomes (1)
Primary Toxicity profile
3 months
Study Arms (3)
A-dmDT390-bisFv(UCHT1)
EXPERIMENTALA-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.
Vorinostat
ACTIVE COMPARATORSubjects 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.
Lead-in Dosing single arm
EXPERIMENTALDose 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.
Interventions
anti-T cell immunotoxin (antibody targeting CD3 on T-cells tagged with diphtheria toxin without binding domain)
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.
Eligibility Criteria
You may qualify if:
- 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.
- +4 more criteria
You may not qualify if:
- 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.
- Congestive heart failure,
- Atrial fibrillation,
- Pulmonary hypertension,
- Anticoagulant drug therapy,
- Thromboembolic events,
- 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 treatment with vorinostat (Prior treatment with vorinostat for lead-in dosing arm is acceptable).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Angimmune LLClead
- City of Hope National Medical Centercollaborator
- Columbia Universitycollaborator
- Dana-Farber Cancer Institutecollaborator
- Northwestern University Feinberg School of Medicinecollaborator
- H. Lee Moffitt Cancer Center and Research Institutecollaborator
- Ohio State University Comprehensive Cancer Centercollaborator
- Rush University Medical Centercollaborator
- Scott and White Hospital & Cliniccollaborator
- Yale Universitycollaborator
- Stanford Universitycollaborator
- Thomas Jefferson Universitycollaborator
- University of Arkansascollaborator
- University of Colorado, Denvercollaborator
- University of Texas Southwestern Medical Centercollaborator
- University of Washingtoncollaborator
- Vanderbilt University School of Medicinecollaborator
- Washington University School of Medicinecollaborator
Related Publications (2)
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.
PMID: 25795722RESULTValipour 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.
PMID: 32632956DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- CROSSOVER
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 18, 2016
First Posted
October 25, 2016
Study Start
January 1, 2017
Primary Completion
December 1, 2018
Study Completion
May 1, 2020
Last Updated
October 25, 2016
Record last verified: 2016-10