Overview

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

Status:
Unknown status
Trial end date:
2020-05-01
Target enrollment:
0
Participant gender:
All
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.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Angimmune LLC
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
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
Yale University
Treatments:
Vorinostat
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).