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A-dmDT390-bisFv(UCHT1) Fusion Protein in Combination With Ionizing Radiation for Treatment of Stage IV Melanoma

Primary Purpose

Melanoma

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

A-dmDT390-bisFv(UCHT1) (Resimmune®)

Ionizing Radiation

About this trial

This is an interventional treatment trial for Melanoma

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

All patients must have histologically proven stage IV metastatic melanoma consisting of at least two lesions
Patients must have a performance status of < 2 on Eastern Cooperative Oncology Group scale (see Appendix).
Patients must have bilirubin < 1.5 mg/dL, transaminases < 2.5 X ULN, albumin > 3 gm/dL, creatinine < 2.0 mg/dL, adequate pulmonary function by physical exam and pulse oximetry and adequate cardiac reserve (EF > 50% normal). Patients must have a normal echocardiogram without any evidence of cardiac chamber hypertrophy, dilatation or hypokinesis.
Patients must give written informed consent prior to registration.
Females and males must be willing to use an approved form of birth control while on this study and for 2 weeks after completion.
Patients of ages 18-80 are eligible provided they have stage IV melanoma and are negative for BRAF or have failed BRAF inhibitor treatment or if they have failed or are intolerant to other established therapy known to provide clinical benefit for their condition or if they have been adequately consented and agreed to forgo FDA approved clinically meaningful therapy

Exclusion Criteria:

Inability to give informed consent because of psychiatric problems, or complicated medical problems.
Serious concurrent medical problems, uncontrolled infections, or disseminated intravascular coagulopathy (DIC).
Preexisting cardiovascular disease, the only exception being well controlled essential hypertension with a sitting blood pressure of <155 systolic and <90 diastolic without any evidence of structural heart disease or one episode of myocardial infarction > 8 months ago. A past history of the any of the following are exclusions: congestive heart failure, atrial fibrillation, pulmonary hypertension, anticoagulant drug therapy, thromboembolic events, cardiomyopathy or a myocardial infarction within the past 8 months.
Pregnant or nursing women will be excluded from study.
History of congestive heart failure.
History of cirrhosis of the liver

Sites / Locations

James Graham Brown Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

A-dmDT390-bisFv(UCHT1) with Ionizing Radiation

Arm Description

A-dmDT390-bisFv(UCHT1) Fusion Protein in Combination With Ionizing Radiation

Outcomes

Primary Outcome Measures

Immune-related overall response rate (irORR)

Response will be assessed at 2 months, and at least every 3 months (±7 days) thereafter using for up to 1 year after the last treatment administration or until evidence of disease progression. Tumor measurements and therapeutic response will be determined using irRC (Immune Related Response Criteria). At a minimum, CT scans of the chest, abdomen, and pelvis will be performed at study entry, at 2 months, and, if a response or stable disease, at least every 3 months (±7 days) for up to 1 year after the last dose of study drug, and/or at any time there is clinical evidence of disease progression, to evaluate disease status.

Secondary Outcome Measures

Overall survival

Survival should be assessed and a physical exam should be completed every three months as per standard of care

Full Information

NCT ID

NCT01888081

First Posted

June 21, 2013

Last Updated

November 22, 2016

Sponsor

Angimmune LLC

Collaborators

University of Louisville

1. Study Identification

Unique Protocol Identification Number

NCT01888081

Brief Title

A-dmDT390-bisFv(UCHT1) Fusion Protein in Combination With Ionizing Radiation for Treatment of Stage IV Melanoma

Official Title

Phase I/II Trial of A-dmDT390-bisFv(UCHT1) Fusion Protein in Combination With Ionizing Radiation for the Treatment of Stage IV Melanoma

Study Type

Interventional

2. Study Status

Record Verification Date

November 2016

Overall Recruitment Status

Terminated

Why Stopped

Protocol replaced with combination therapy adding KEYTRUDA (pembrolizumab)

Study Start Date

February 2014 (undefined)

Primary Completion Date

December 2020 (Anticipated)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Angimmune LLC

Collaborators

University of Louisville

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of this trial is to study A-dmDT390-bisFv(UCHT1) in combination with ionizing irradiation for the treatment of stage IV melanoma, a disease that is essentially incurable with median overall survival periods that range from 8-16 months.

Detailed Description

A-dmDT390-bisFv(UCHT1) (Resimmune™), an anti-T cell immunotoxin is currently being studied as a treatment for cutaneous T cell lymphoma and other CD3+ malignant diseases (FDA IND Number: 100712, Scott and White Protocol 071163). During the course of this study, data accumulated that Resimmune could be acting as an immunomodulator. This was based on the observation that four out of six partial responses converted to complete responses at times ranging between 6 and 24 months following the completion of the 4-day treatment protocol and no other treatment took place. The purpose of this trial is to test the hypothesis that Resimmune can act as an immunomodulator of late stage metastatic melanoma when combined with palliative radiation to induce the priming of activated T cells with tumor antigens. The primary objective of this study is to determine the safety of combining Resimmune with palliative radiation therapy in patients with stage IV melanoma. A secondary objective is to document the tumor response and duration of response at irradiated and unirradiated sites (the abscopal effect). An additional secondary objective is to determine if T cell activation occurs following administration of A-dmDT390-bisFv(UCHT1) and local radiation to a metastatic lesion of melanoma.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Melanoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

2 (Actual)

8. Arms, Groups, and Interventions

Arm Title

A-dmDT390-bisFv(UCHT1) with Ionizing Radiation

Arm Type

Experimental

Arm Description

A-dmDT390-bisFv(UCHT1) Fusion Protein in Combination With Ionizing Radiation

Intervention Type

Drug

Intervention Name(s)

A-dmDT390-bisFv(UCHT1) (Resimmune®)

Intervention Type

Radiation

Intervention Name(s)

Ionizing Radiation

Primary Outcome Measure Information:

Title

Immune-related overall response rate (irORR)

Description

Time Frame

For up to 1 year post treatment or until disease progression

Secondary Outcome Measure Information:

Title

Overall survival

Description

Survival should be assessed and a physical exam should be completed every three months as per standard of care

Time Frame

every 3 months for up to 3 years

Other Pre-specified Outcome Measures:

Title

Treatment Duration

Description

Patients will be admitted to the hospital on day 0 for the first two infusions on day 1. Infusions for days 2, 3 and 4 and fractionated radiation will be done in the clinic on an outpatient basis.

Time Frame

4 Days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: All patients must have histologically proven stage IV metastatic melanoma consisting of at least two lesions Patients must have a performance status of < 2 on Eastern Cooperative Oncology Group scale (see Appendix). Patients must have bilirubin < 1.5 mg/dL, transaminases < 2.5 X ULN, albumin > 3 gm/dL, creatinine < 2.0 mg/dL, adequate pulmonary function by physical exam and pulse oximetry and adequate cardiac reserve (EF > 50% normal). Patients must have a normal echocardiogram without any evidence of cardiac chamber hypertrophy, dilatation or hypokinesis. Patients must give written informed consent prior to registration. Females and males must be willing to use an approved form of birth control while on this study and for 2 weeks after completion. Patients of ages 18-80 are eligible provided they have stage IV melanoma and are negative for BRAF or have failed BRAF inhibitor treatment or if they have failed or are intolerant to other established therapy known to provide clinical benefit for their condition or if they have been adequately consented and agreed to forgo FDA approved clinically meaningful therapy Exclusion Criteria: Inability to give informed consent because of psychiatric problems, or complicated medical problems. Serious concurrent medical problems, uncontrolled infections, or disseminated intravascular coagulopathy (DIC). Preexisting cardiovascular disease, the only exception being well controlled essential hypertension with a sitting blood pressure of <155 systolic and <90 diastolic without any evidence of structural heart disease or one episode of myocardial infarction > 8 months ago. A past history of the any of the following are exclusions: congestive heart failure, atrial fibrillation, pulmonary hypertension, anticoagulant drug therapy, thromboembolic events, cardiomyopathy or a myocardial infarction within the past 8 months. Pregnant or nursing women will be excluded from study. History of congestive heart failure. History of cirrhosis of the liver

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jason Chesney, MD, PhD

Organizational Affiliation

James Graham Brown Cancer Center, University of Louisville

Official's Role

Principal Investigator

Facility Information:

Facility Name

James Graham Brown Cancer Center

City

Louisville

State/Province

Kentucky

ZIP/Postal Code

40202

Country

United States

12. IPD Sharing Statement

Learn more about this trial

A-dmDT390-bisFv(UCHT1) Fusion Protein in Combination With Ionizing Radiation for Treatment of Stage IV Melanoma

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