O6-Benzylguanine and Topical Carmustine in Treating Patients With Early-Stage IA-IIA Cutaneous T-Cell Lymphoma

NCT00961220 | Completed Phase 1 Results DMC

• 7 other identifiers: NCI-2012-029273405CASE 3405-CC3047080P30CA043703R21CA115057U01CA062502
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 4

Brief Summary

This phase I/II trial studies the side effects and best dose of carmustine when given together with O6-benzylguanine and to see how well they work in treating patients with stage IA-IIA cutaneous T-cell lymphoma. Drugs used in chemotherapy, such as carmustine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. O6-benzylguanine may help carmustine work better by making cancer cells more sensitive to the drug. Giving O6-benzylguanine with carmustine may kill more cancer cells.

Conditions

Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage I Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage II Mycosis Fungoides and Sezary Syndrome AJCC v7

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  Based on changes in modified SWAT assessment, patient responses will be classified as complete clinical response (CCR), partial response (PR), stable disease (SD), or progressive disease (PD). SWAT provides an accurate and reproducible assessment of cutaneous disease involvement based on body surface area of involvement and lesional thickness. CCR: No evidence of disease, 100% improvement for a duration of at least 4 weeks. PR: Greater than or equal to 50% decrease in SWAT score compared to baseline and improvement is maintained for at least 4 weeks. SD: Less than 50% decrease in SWAT score compared to baseline. PD: Increase of greater or equal to 25% of the SWAT score compared to baseline while the patient is actively taking the study drug

  Up to 2 weeks after completion of study treatment

Secondary Outcomes (12)

• Changes in AGT (O6-alkylguanine DNA Alkyltransferase) Activity

  Baseline

• Changes in AGT (O6-alkylguanine DNA Alkyltransferase) Activity

  24 hours after the first infusion

• Changes in AGT (O6-alkylguanine DNA Alkyltransferase) Activity

  48 hours after the first infusion

• Changes in AGT (O6-alkylguanine DNA Alkyltransferase) Activity

  1 week after the first infusion

• Changes in the Apoptosis

  at 24 hours after the first infusion

Study Arms (1)

Treatment (O6-benzylguanine, carmustine)

EXPERIMENTAL

Patients receive O6-benzylguanine IV over 1 hour and apply topical carmustine to the total skin surface (excluding the lips, eyelids, and ulcerated lesions) 1 hour after completing O6-benzylguanine infusion on days 1-2. Treatment repeats every 2 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Drug: Carmustine; Other: Laboratory Biomarker Analysis; Drug: O6-Benzylguanine

Interventions

Carmustine DRUG

Applied topically

Also known as: BCNU, Becenum, Becenun, BiCNU, Bis(chloroethyl) Nitrosourea, Bis-Chloronitrosourea, Carmubris, Carmustin, Carmustinum, FDA 0345, Gliadel, N,N'-Bis(2-chloroethyl)-N-nitrosourea, Nitrourean, Nitrumon, SK 27702, SRI 1720, WR-139021

Treatment (O6-benzylguanine, carmustine)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (O6-benzylguanine, carmustine)

O6-Benzylguanine DRUG

Given IV

Also known as: 6-O-Benzylguanine, O(6)-Benzylguanine

Treatment (O6-benzylguanine, carmustine)

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of CTCL stages IA-IIA by histopathology and immunohistochemistry in screening biopsies confirmed at Case Western Reserve University within 6 months of enrollment; biopsies may be performed at the site of collaborating institutions and shipped to University Hospitals of Cleveland-Case Western Reserve University (UHC-CWRU)
• Performance status Eastern Cooperative Oncology Group (ECOG) grade 0, 1, or 2
• Patients must have recovered from toxicity of prior treatment and have received no CTCL therapy other than emollition for at least 4 weeks, with the exception of topical corticosteroids, which may be used up to 2 weeks before the trial start date
• Patients must have signed a consent form indicating the investigational nature of the treatment and its potential side effects
• White blood cell (WBC) at least 3.5 x10E9/L
• Absolute neutrophil count (ANC) at least 1.6 x10E9/L
• Platelets \> 100,000/ul
• Bilirubin \< 1.5 mg/dL
• Serum glutamic oxaloacetic transaminase (SGOT) within normal range
• Creatinine =\< 1.5 mg/dL
• Electrolytes normal
• Controlled (diet and insulin) diabetes is permitted
• Patients must have cutaneous disease that is amenable to biopsy and must be willing to undergo several sequential biopsies
• Must have failed at least one conventional treatment for CTCL other than topical corticosteroids; this includes phototherapy, topical mechlorethamine, topical or oral bexarotene, radiation therapy, photopheresis, chemotherapy, and immunomodulatory agents such as interferon and other retinoids

You may not qualify if:

• Patients who have received prior treatment with topical or systemic BCNU or other nitrosoureas
• Patients with known central nervous system involvement or primary central nervous system (CNS) malignancies
• Patients with performance status ECOG grade 3 or 4
• Pregnant women, women who are breast feeding infants, or women with reproductive potential not practicing adequate contraception
• Patients with an active infection which requires hospitalization, or which may affect the patient?s safety if the patient was enrolled
• Patients with pulmonary disease as determined by history, physical examination, chest X-ray, or pulse oximetry with \< 70% predicted DLCO
• CTCL patients with stage IIB-IVB disease

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (4)

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Case Comprehensive Cancer Center

Cleveland, Ohio, 44106-5065, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Publications (1)

• Tacastacas JD, Chan DV, Carlson S, Gerson SL, Dowlati A, Fu P, Lu K, Groft S, Rosenjack J, Honda K, McCormick TS, Cooper KD. Evaluation of O6-Benzylguanine-Potentiated Topical Carmustine for Mycosis Fungoides: A Phase 1-2 Clinical Trial. JAMA Dermatol. 2017 May 1;153(5):413-420. doi: 10.1001/jamadermatol.2016.5793.

  PMID: 28199478 DERIVED

MeSH Terms

Conditions

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

Interventions

Carmustine; carmustine, poliferprosan 20 drug combination; O(6)-benzylguanine

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds

Results Point of Contact

• Title: Dr. Kevin Cooper
• Organization: Case Comprehensive Cancer Center

kevin.cooper@uhhospitals.org

216-844-3111

Study Officials

• Kevin Cooper

  Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 16, 2009
• First Posted: August 18, 2009
• Study Start: February 1, 2010
• Primary Completion: April 8, 2012
• Study Completion: April 8, 2014
• Last Updated: May 22, 2018
• Results First Posted: March 23, 2015

Record last verified: 2018-04

Locations

US (4)