A-dmDT390-bisFv(UCHT1) Immunotoxin Therapy for Patients With Cutaneous T-Cell Lymphoma (CTCL)

NCT00611208 | Completed Phase 2 DMC

• 1 other identifier: FDA IND 100712
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 5

Brief Summary

This is a Phase II clinical trial aimed at treating a subgroup of patients with cutaneous T-cell lymphoma. The drug consists of a toxin, called diphtheria toxin, which is attached to an antibody that can specifically target cancerous T-cells. Our primary objectives are, therefore, to determine the patient subgroup with respect to disease burden who best responds to this experimental drug in treating CD3 positive T cell malignancies. We will be determining how the patient and their disease respond to this research agent. The Clinical Response Data analysis from October 2014 done at the completion of the Phase I portion of A-dmT390-bisFv(UCHT1) fusion protein clinical trial showed that there were 25 evaluable patients who received all 8 doses varying between 2.5 and 11.25 µg/kg per dose. There were responses at all the lower dose levels up to 7.5 µg/kg per dose. The overall response rate was 36% and the complete response rate was 16% (when followed for 6 months). We have identified a subgroup of CTCL patients that have a very high response rate. If we exclude patients whose mSWAT scores never exceeded 50 (50% of skin surface area times a multiplier) and who never had lymph node involvement or stage III disease we are left with 9 patients. This subgroup has an overall response rate of 89% and a complete response rate of 50% (when followed for 6 months). Of these 4 patients currently in complete remission, three are long-term responders. Two are over 6 years in duration and one over 5 years duration. These may represent cures. The long time periods in the transition from partial response to complete response without treatment, 6 months to two years, suggests that the study drug in addition to exerting a direct killing effect on tumor also functions as an immunomodulator.

Conditions

T-cell Lymphomas; T-cell Leukemia; Sezary Syndrome; Mycosis Fungoides; Cutaneous T-cell Lymphoma (CTCL)

Outcome Measures

Primary Outcomes (1)

• Remission status (complete, partial, stable disease, progressive disease)

  Time Frame: 6 years

Study Arms (1)

A-dmDT390-bisFv(UCHT1)

EXPERIMENTAL

anti-T cell immunotoxin (antibody targeting CD3 on T-cells tagged with diptheria toxin)

Biological: A-dmDT390-bisFv(UCHT1)

Interventions

A-dmDT390-bisFv(UCHT1) BIOLOGICAL

A-dmDT390-bisFv(UCHT1) will be administered as 60 μg/kg total given as 7.5 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

Also known as: Resimmune®

A-dmDT390-bisFv(UCHT1)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have signed the current Institutional Review Board (IRB) approved informed consent prior to registration (see Informed Consent).
• All patients must have CTCL diagnosed by morphologic, histochemical or cell surface marker criteria with stage never exceeding IB / IIB disease and mSWAT \< 50%. CTCL patients with stage IA disease are not eligible for enrollment. CTCL patients with stage IB disease are eligible provided that they have failed a systemic treatment (this includes radiation). CTCL patients with bone marrow involvement but without lymph node involvement are eligible. Patients with a diagnosis of angioimmunoblastic T cell lymphoma are eligible, even with lymph node involvement. Age ≥ 18 years. Patients must have a performance status of \< 2 on Eastern Cooperative Oncology Group scale (see Appendix). Patients must have fully recovered from toxicity of prior chemotherapy or radiation therapy.
• Patients must have bilirubin \< 1.5 mg/dL, transaminases \< 2.5 X ULN, albumin \> 3 gm/dL, creatinine \< 2.0 mg/dL. Patients who have had albumin \< 3 gm/dL boosted by an albumin infusion must be observed to maintain albumin at \> 3gm dL for 30 days without an additional infusion.
• Patients must have a normal echocardiogram (EF \> 50% normal) without any evidence of cardiac chamber hypertrophy, dilatation or hypokinesis. The Sponsor must be provided with copies of these tests BEFORE Sponsor will approve enrollment. In addition, the sponsor must receive a list of current medications taken by the patient before Sponsor will approve enrollment.
• Females and males must be willing to use an approved form of birth control while on this study and for 2 weeks after completion.

You may not qualify if:

• Failure to meet any of the criteria set forth in Section 3.1.
• 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,
• Cardiomyopathy or a myocardial infarction within the past 8 months.
• 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. (Appendix B.)
• 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.

Sponsors & Collaborators

• Angimmune LLC: lead
• James Graham Brown Cancer Center: collaborator
• M.D. Anderson Cancer Center: collaborator
• Scott and White Hospital & Clinic: collaborator
• University of Texas Southwestern Medical Center: collaborator
• Yale University: collaborator

Study Sites (5)

Yale University School Of Medicine Recruiting

New Haven, Connecticut, 06520, United States

Location

James Graham Brown Cancer Center

Louisville, Kentucky, 40202, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390-8562, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Scott and White Hospital & Clinic

Temple, Texas, 76508, United States

Location

Related Publications (4)

• Frankel AE, Zuckero SL, Mankin AA, Grable M, Mitchell K, Lee YJ, Neville DM, Woo JH. Anti-CD3 recombinant diphtheria immunotoxin therapy of cutaneous T cell lymphoma. Curr Drug Targets. 2009 Feb;10(2):104-9. doi: 10.2174/138945009787354539.

  PMID: 19199905 RESULT

• Frankel, Arthur E. Anti-CD3 immunotoxin to induce remissions in cutaneous T-cell lymphoma patients. Poster session presented at: 2012 American Society of Clinical Oncology (ASCO). Oral Abstract Session, Developmental Therapeutics - Clinical Pharmacology and Immunotherapy. 2012 June 1-5; Chicago, IL.

  RESULT

• Arthur E. Frankel, Jung H. Woo, Jeremy P. Mauldin, Francine M. Foss, Madeleine Duvic, David M. Neville Jr. An Update On The Clinical Activity Of Resimmune, a Targeted Therapy Directed To CD3 Receptor, In Patients With Cutaneous T Cell Lymphomas-CTCL. Poster session presented at: 2012 American Society of Hematology (ASH). 55th ASH Annual Meeting and Exposition. 2013 December 7-10; New Orleans, LA.

  RESULT

• 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: 25795722 RESULT

Related Links

• ASH 2013 Abstract

MeSH Terms

Conditions

Lymphoma, T-Cell; Leukemia, T-Cell; Sezary Syndrome; Mycosis Fungoides; Lymphoma, T-Cell, Cutaneous

Interventions

A-dmDT390-bisFv(UCHT1) protein

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Lymphoid; Leukemia; Hematologic Diseases

Study Officials

• Arthur E Frankel, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

• Madeleine Duvic, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

• Cesar Rodriguez, MD

  James Graham Brown Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2008
• First Posted: February 8, 2008
• Study Start: January 1, 2008
• Primary Completion: February 1, 2015
• Study Completion: November 1, 2016
• Last Updated: November 29, 2016

Record last verified: 2016-11

Locations

US (5)