Trial Outcomes & Findings for O6-Benzylguanine and Topical Carmustine in Treating Patients With Early-Stage IA-IIA Cutaneous T-Cell Lymphoma (NCT NCT00961220)

NCT ID: NCT00961220

Last Updated: 2018-05-22

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 17 participants
• Primary outcome timeframe: Up to 2 weeks after completion of study treatment
• Results posted on: 2018-05-22

Participant Flow

Patients were recruited from February 2010 to November 2013 from University Hospital Case Medical Center.

Participant milestones

Measure	Treatment (O6-benzylguanine, Carmustine) 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. O6-benzylguanine: Given IV. 120 mg/m2 over 1 hour Carmustine (BCNU) will begin at a starting dose of 20 mg on Day 1. Beyond this first dose level, for each of the subsequent four patients enrolled, the BCNU dose will be escalated up to a limit of 40 mg total (given on day 1 only). laboratory biomarker analysis: Correlative studies
Overall Study STARTED	17
Overall Study COMPLETED	10
Overall Study NOT COMPLETED	7

Reasons for withdrawal

Measure	Treatment (O6-benzylguanine, Carmustine) 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. O6-benzylguanine: Given IV. 120 mg/m2 over 1 hour Carmustine (BCNU) will begin at a starting dose of 20 mg on Day 1. Beyond this first dose level, for each of the subsequent four patients enrolled, the BCNU dose will be escalated up to a limit of 40 mg total (given on day 1 only). laboratory biomarker analysis: Correlative studies
Overall Study Adverse Event	3
Overall Study Lack of Efficacy	1
Overall Study No IV access for O6BG	1
Overall Study O6BG no longer supplied	1
Overall Study Complete Response prior to 12 courses	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Treatment (O6-benzylguanine, Carmustine) n=17 Participants 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. O6-benzylguanine: Given IV. 120 mg/m2 over 1 hour Carmustine (BCNU) will begin at a starting dose of 20 mg on Day 1. Beyond this first dose level, for each of the subsequent four patients enrolled, the BCNU dose will be escalated up to a limit of 40 mg total (given on day 1 only). laboratory biomarker analysis: Correlative studies
Age, Customized 20-29 years	2 participants n=93 Participants
Age, Customized 30-39 years	5 participants n=93 Participants
Age, Customized 40-49 years	4 participants n=93 Participants
Age, Customized 50-59 years	2 participants n=93 Participants
Age, Customized 60-69 years	3 participants n=93 Participants
Age, Customized 70-79 years	1 participants n=93 Participants
Sex: Female, Male Female	5 Participants n=93 Participants
Sex: Female, Male Male	12 Participants n=93 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	17 Participants n=93 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	5 Participants n=93 Participants
Race (NIH/OMB) White	12 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Region of Enrollment United States	17 participants n=93 Participants

PRIMARY outcome

Timeframe: Up to 2 weeks after completion of study treatment

Population: Intention to treat

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

Outcome measures

Measure	Treatment (O6-benzylguanine, Carmustine) n=17 Participants 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. O6-benzylguanine: Given IV carmustine: Applied topically laboratory biomarker analysis: Correlative studies
Overall Response Rate Complete Clinical Response-unconfirmed	2 participants
Overall Response Rate Partial Response	8 participants
Overall Response Rate Progressive Disease	1 participants
Overall Response Rate Complete Clinical Response-confirmed	6 participants

SECONDARY outcome

Timeframe: Baseline

Population: Attempts to stain AGT and caspase 3 were unsuccessful and there were no remaining tissues for other outcomes.

Examine AGT depletion at baseline, 24 hrs or 48 hrs, and 1 week after the first Infusion of O6BG. AGT levels will be determined by biochemical activity assay.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 24 hours after the first infusion

Population: Attempts to stain AGT and caspase 3 were unsuccessful and there were no remaining tissues for other outcomes.

Examine AGT depletion at baseline, 24 hrs or 48 hrs, and 1 week after the first Infusion of O6BG. AGT levels will be determined by biochemical activity assay.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 48 hours after the first infusion

Population: Attempts to stain AGT and caspase 3 were unsuccessful and there were no remaining tissues for other outcomes.

Examine AGT depletion at baseline, 24 hrs or 48 hrs, and 1 week after the first Infusion of O6BG. AGT levels will be determined by biochemical activity assay.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 week after the first infusion

Population: Attempts to stain AGT and caspase 3 were unsuccessful and there were no remaining tissues for other outcomes.

Examine AGT depletion at baseline, 24 hrs or 48 hrs, and 1 week after the first Infusion of O6BG. AGT levels will be determined by biochemical activity assay.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: at 24 hours after the first infusion

Population: Attempts to stain AGT and caspase 3 were unsuccessful and there were no remaining tissues for other outcomes.

Comparing skin biopsy specimens of BCNU-protected CTCL lesional specimens vs BCNU-treated lesional specimens at 24 hours, using immunohistochemical staining for Ki-67, PCNA, bcl-2, and caspase-3, as well as y2HAX and TUNEL assays. The apoptotic index will be calculated from these results.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: at 48 hours after the first infusion

Population: Attempts to stain AGT and caspase 3 were unsuccessful and there were no remaining tissues for other outcomes.

Comparing skin biopsy specimens of BCNU-protected CTCL lesional specimens vs BCNU-treated lesional specimens at 48 hours, using immunohistochemical staining for Ki-67, PCNA, bcl-2, and caspase-3, as well as y2HAX and TUNEL assays. The apoptotic index will be calculated from these results.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: at 24 hours after the first infusion

Population: Attempts to stain AGT and caspase 3 were unsuccessful and there were no remaining tissues for other outcomes.

Comparing skin biopsy specimens of BCNU-protected CTCL lesional specimens vs BCNU-treated lesional specimens at 24 hours, using immunohistochemical staining for Ki-67, PCNA, bcl-2, and caspase-3, as well as y2HAX and TUNEL assays. The proliferation rate will be calculated from these results.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: at 48 hours after the first infusion

Population: Attempts to stain AGT and caspase 3 were unsuccessful and there were no remaining tissues for other outcomes.

Comparing skin biopsy specimens of BCNU-protected CTCL lesional specimens vs BCNU-treated lesional specimens at 48 hours, using immunohistochemical staining for Ki-67, PCNA, bcl-2, and caspase-3, as well as y2HAX and TUNEL assays. The proliferation rate will be calculated from these results.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 24 hours after the first infusion

Population: Attempts to stain AGT and caspase 3 were unsuccessful and there were no remaining tissues for other outcomes.

Immunohistochemistry will be used to assess expression of these proteins in keratinocytes, epidermal lymphocytes, and dermal lymphocytes, to determine the effects of BCNU cytotoxicity in each subpopulation of cells

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 48 hours after the first infusion

Population: Attempts to stain AGT and caspase 3 were unsuccessful and there were no remaining tissues for other outcomes.

Immunohistochemistry will be used to assess expression of these proteins in keratinocytes, epidermal lymphocytes, and dermal lymphocytes, to determine the effects of BCNU cytotoxicity in each subpopulation of cells

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: After first course at 2 weeks

Population: Attempts to stain AGT and caspase 3 were unsuccessful and there were no remaining tissues for other outcomes.

Changes in AGT levels will be determined by biochemical activity assay from first course to seventh course of treatment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: After seventh course at 14 weeks

Population: Attempts to stain AGT and caspase 3 were unsuccessful and there were no remaining tissues for other outcomes.

Changes in AGT levels will be determined by biochemical activity assay from first course to seventh course of treatment.

Outcome measures

Outcome data not reported

Adverse Events

Treatment (O6-benzylguanine, Carmustine)

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Treatment (O6-benzylguanine, Carmustine) n=17 participants at risk 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. O6-benzylguanine: Given IV. 120 mg/m2 over 1 hour Carmustine (BCNU) will begin at a starting dose of 20 mg on Day 1. Beyond this first dose level, for each of the subsequent four patients enrolled, the BCNU dose will be escalated up to a limit of 40 mg total (given on day 1 only). laboratory biomarker analysis: Correlative studies
Skin and subcutaneous tissue disorders ACNEIFORM RASH	5.9% 1/17 • Adverse events were collected from during treatment over a 6 month time period.
Investigations ALKALINE PHOSPHATASE ELEVATED	5.9% 1/17 • Adverse events were collected from during treatment over a 6 month time period.
Blood and lymphatic system disorders ANEMIA	17.6% 3/17 • Adverse events were collected from during treatment over a 6 month time period.
Gastrointestinal disorders BLOATING	5.9% 1/17 • Adverse events were collected from during treatment over a 6 month time period.
Gastrointestinal disorders CONSTIPATION	5.9% 1/17 • Adverse events were collected from during treatment over a 6 month time period.
Investigations CREATININE ELEVATION	5.9% 1/17 • Adverse events were collected from during treatment over a 6 month time period.
Skin and subcutaneous tissue disorders CUTANEOUS HYPERPIGMENTATION	70.6% 12/17 • Adverse events were collected from during treatment over a 6 month time period.
Nervous system disorders DIZZINESS	11.8% 2/17 • Adverse events were collected from during treatment over a 6 month time period.
Skin and subcutaneous tissue disorders DRY SKIN	11.8% 2/17 • Adverse events were collected from during treatment over a 6 month time period.
General disorders FATIGUE	58.8% 10/17 • Adverse events were collected from during treatment over a 6 month time period.
Metabolism and nutrition disorders GLUCOSE LOW	5.9% 1/17 • Adverse events were collected from during treatment over a 6 month time period.
Nervous system disorders HEADACHE	47.1% 8/17 • Adverse events were collected from during treatment over a 6 month time period.
General disorders INJECTION SITE REACTION or PAIN	11.8% 2/17 • Adverse events were collected from during treatment over a 6 month time period.
Musculoskeletal and connective tissue disorders JOINT PAINS	5.9% 1/17 • Adverse events were collected from during treatment over a 6 month time period.
Blood and lymphatic system disorders LEUKOPENIA	5.9% 1/17 • Adverse events were collected from during treatment over a 6 month time period.
Blood and lymphatic system disorders MONOCYTE ELEVATION	5.9% 1/17 • Adverse events were collected from during treatment over a 6 month time period.
Musculoskeletal and connective tissue disorders MYALGIA	5.9% 1/17 • Adverse events were collected from during treatment over a 6 month time period.
Gastrointestinal disorders NAUSEA	47.1% 8/17 • Adverse events were collected from during treatment over a 6 month time period.
Skin and subcutaneous tissue disorders PAIN OF SKIN	52.9% 9/17 • Adverse events were collected from during treatment over a 6 month time period.
Skin and subcutaneous tissue disorders PRURITUS	52.9% 9/17 • Adverse events were collected from during treatment over a 6 month time period.
Skin and subcutaneous tissue disorders RASH/ DESQUAMATION	64.7% 11/17 • Adverse events were collected from during treatment over a 6 month time period.
Skin and subcutaneous tissue disorders SKIN ULCERATION	5.9% 1/17 • Adverse events were collected from during treatment over a 6 month time period.
Skin and subcutaneous tissue disorders TELANGIECTASIA	5.9% 1/17 • Adverse events were collected from during treatment over a 6 month time period.
Investigations TOTAL BILIRUBIN ELEVATED	5.9% 1/17 • Adverse events were collected from during treatment over a 6 month time period.
Investigations TRANSAMINASE ELEVATION	52.9% 9/17 • Adverse events were collected from during treatment over a 6 month time period.
Renal and urinary disorders URIC ACID ELEVATION	11.8% 2/17 • Adverse events were collected from during treatment over a 6 month time period.
Renal and urinary disorders URINE SPECIFIC GRAVITY ELEVATED	11.8% 2/17 • Adverse events were collected from during treatment over a 6 month time period.

Additional Information

Dr. Kevin Cooper

Case Comprehensive Cancer Center

Phone: 216-844-3111

Email: kevin.cooper@uhhospitals.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60