Safety and Efficacy of Nitrogen Mustard in Treatment of Mycosis Fungoides

• Sponsor: Yaupon Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00168064
• Collaborator: (none)
• Enrollment: 260
• Locations: 12
• Arms: 2
• Duration (Months): 63
• Patients Per Site: 21.7
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This study will evaluate the efficacy, tolerability and safety of the topical application of mechlorethamine (MCH) formulations in patients with stage I or IIA mycosis fungoides (MF).

Condition or Disease	Intervention/Treatment	Phase
Mycosis Fungoides	Drug: mechlorethamine-MCH (nitrogen mustard)	Phase 2

Detailed Description

The successful use of mechlorethamine (MCH) as a topical agent in the treatment of mycosis fungoides, a form of cutaneous T-cell lymphoma, was first reported in the late 1950s, and provided a rationale for skin-directed chemotherapy that minimized systemic toxicity. Since then, multiple investigators have demonstrated the safety and efficacy of topically applied MCH in the treatment of mycosis fungoides. This study will evaluate the efficacy (non-inferiority), tolerability and safety of topical application of MCH proprietary gel versus a compounded ointment formulation in Aquaphor in patients with stage I or IIA MF.

Study Design

• Study Type: Interventional
• Actual Enrollment: 260 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase II Pivotal Trial to Evaluate the Safety and Efficacy of Nitrogen Mustard (NM) 0.02% Ointment Formulations in Patients With Stage I or IIA Mycosis Fungoides (MF)
• Study Start Date: May 1, 2006
• Actual Primary Completion Date: Aug 1, 2010
• Actual Study Completion Date: Aug 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 (PG - NM (MCH) 0.02%) PG - mechlorethamine-MCH (nitrogen mustard) 0.02% gel To evaluate the tolerability and safety of topical mechlorethamine-MCH (nitrogen mustard) 0.02% ointment formulations in patients with stage I or IIA MF	Drug: mechlorethamine-MCH (nitrogen mustard); All affected areas (lesions) are to be treated once daily for twelve months with mechlorethamine-MCH (nitrogen mustard) 0.02% PG or NM 0.02% AP ointment; Other Names: mechlorethamine nitrogen mustard
Active Comparator: 2 (AP - MCH(NM) 0.02%) AP - mechlorethamine-MCH (nitrogen mustard) 0.02% compounded in Aquaphor To evaluate the tolerability and safety of mechlorethamine-MCH (nitrogen mustard)0.02% ointment formulations in patients with stage I or IIA MF	Drug: mechlorethamine-MCH (nitrogen mustard); All affected areas (lesions) are to be treated once daily for twelve months with mechlorethamine-MCH (nitrogen mustard) 0.02% PG or NM 0.02% AP ointment; Other Names: mechlorethamine nitrogen mustard

Outcome Measures

Primary Outcome Measures

1. Ratio of Response Rates Based on CAILS [Assessment made at Day 1 and every subsequent visit during treatment]

   The ratio of the response rate of the patients treated with the PG formulation to the response rate of the patients treated with the AP formulation. Skin response determined by at least a 50% reduction from baseline in the Composite Assessment of Index Lesion Severity (CAILS) following up to 12 months of treatment

Secondary Outcome Measures

1. Severity-weighted Assessment Tool (SWAT) Within up to 12 Months by 2 or More Consecutive Observations Over at Least 4 Weeks [Assessment made at Day 1 and every subsequent visit during treatment]

2. Percent of Participants Achieving at Least 50% Improvement of Severity Weighted Assessment Tool (SWAT) [Baseline to end of therapy]

   Assessment of lesion distribution and severity. A responder analysis was performed on whether subject achieved at least 50% improvement on scale. This had to be confirmed on at least one visit at least 4 weeks apart.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with mycosis fungoides confirmed by a skin biopsy

• Stage I or IIA patients must have been treated previously with prior topical therapies including PUVA, UVB, topical steroids, but not NM within the past 2 years, or topical carmustine (BCNU)

• Patients must be otherwise healthy with acceptable organ function.

• Prior to initiating study therapy, patients must not have had topical therapy within four weeks

• Lab values within normal range

• Willing/able to give consent

• Must use effective means of contraception if of childbearing potential

Exclusion Criteria:

• Newly diagnosed mycosis fungoides with no prior therapy

• A prior history of treatment with topical NM within the past 2 years or topical carmustine (BCNU)

• Use of topical or systemic therapies for MF within four (4) weeks of entry in the study

• Patients with a diagnosis of stage IIB-IV MF

• Serious known concurrent medical illness or infection, which could potentially present a safety risk and/or prevent compliance with the requirements of the treatment program

• Pregnant or nursing females, or males and females of childbearing potential, not using an effective means of contraception

• Patients who have had radiation therapy within one year of study start

• Patients who have a history of a higher T score than T2 or a higher N score than N1

• Patients who do not agree to do all labs at one site

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University Medical Center	Stanford	California	United States	94305
2	Northwestern University - Dept. of Dermatology	Chicago	Illinois	United States	61611
3	NYU Medical Center Dept. of Dermatology	New York	New York	United States	10016
4	Columbia University, Dept. of Dermatology	New York	New York	United States	10032
5	Duke University Medical Center	Durham	North Carolina	United States	27710
6	Oklahoma University	Tulsa	Oklahoma	United States	74104
7	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
8	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111-2497
9	University of Texas, Southwestern Medical Center	Dallas	Texas	United States	75390
10	The University of Texas, M.D. Anderson Cancer Center	Houston	Texas	United States	77030
11	Utah Clinical Trials, LLC	Salt Lake City	Utah	United States	84107
12	University of Wisconsin	Madison	Wisconsin	United States	53791

Sponsors and Collaborators

• Yaupon Therapeutics

Investigators

• Study Director: Stuart Lessin, M.D., Fox Chase Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

• Kim YH, Jensen RA, Watanabe GL, Varghese A, Hoppe RT. Clinical stage IA (limited patch and plaque) mycosis fungoides. A long-term outcome analysis. Arch Dermatol. 1996 Nov;132(11):1309-13.
• Kim YH, Martinez G, Varghese A, Hoppe RT. Topical nitrogen mustard in the management of mycosis fungoides: update of the Stanford experience. Arch Dermatol. 2003 Feb;139(2):165-73.
• Kim YH. Management with topical nitrogen mustard in mycosis fungoides. Dermatol Ther. 2003;16(4):288-98. Review.

• Responsible Party: Yaupon Therapeutics
• ClinicalTrials.gov Identifier: NCT00168064
• Other Study ID Numbers: 2005NMMF-201-US
• First Posted: Sep 14, 2005
• Last Update Posted: Oct 31, 2012
• Last Verified: Oct 1, 2012

• Keywords provided by Yaupon Therapeutics: Mycosis Fungoides; Nitrogen Mustard; Cutaneous T-Cell Lymphoma; CTCL - Mycosis Fungoides
• Additional relevant MeSH terms: Mycoses; Mycosis Fungoides; Mechlorethamine; Nitrogen Mustard Compounds

Study Results

Participant Flow

Arm/Group Title	PG -Mechlorethamine (Nitrogen Mustard) 0.02% PG Gel	AP- Mechlorethamine 0.02% Compounded in Aquaphor
Arm/Group Description	Study formulation of Mechlorethamine-MCH (Nitrogen Mustard) 0.02% Gel	Compounded Mechlorethamine-MCH (Nitrogen Mustard) in Aquaphor 0.02%
Period Title: Overall Study
STARTED	130	130
COMPLETED	81	86
NOT COMPLETED	49	44

Baseline Characteristics

Arm/Group Title	PG -Mechlorethamine-MCH (Nitrogen Mustard) 0.02% PG Gel	AP- Mechlorethamine-MCH (NM) 0.02% Compounded in Aquaphor	Total
Arm/Group Description	Study formulation of mechlorethamine-MCH (Nitrogen Mustard) 0.02% Gel	Compounded mechlorethamine-MCH (Nitrogen Mustard)in Aquaphor 0.02%	Total of all reporting groups
Overall Participants	130	130	260
Age (Count of Participants)
<=18 years	0 0%	1 0.8%	1 0.4%
Between 18 and 65 years	93 71.5%	86 66.2%	179 68.8%
>=65 years	37 28.5%	43 33.1%	80 30.8%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.7 (14.20)	56.7 (14.34)	55.7 (14.28)
Sex: Female, Male (Count of Participants)
Female	53 40.8%	53 40.8%	106 40.8%
Male	77 59.2%	77 59.2%	154 59.2%
Region of Enrollment (participants) [Number]
United States	130 100%	130 100%	260 100%

Outcome Measures

1. Primary Outcome

Title	Ratio of Response Rates Based on CAILS
Description	The ratio of the response rate of the patients treated with the PG formulation to the response rate of the patients treated with the AP formulation. Skin response determined by at least a 50% reduction from baseline in the Composite Assessment of Index Lesion Severity (CAILS) following up to 12 months of treatment
Time Frame	Assessment made at Day 1 and every subsequent visit during treatment

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	PG- Mechlorethamine-MCH (Nitrogen Mustard) 0.02% Gel	AP- Aquaphor Formulation Mechlorethamine-MCH (NM) 0.02%
Arm/Group Description	Study formulation of mechlorethamine-MCH (Nitrogen Mustard) 0.02% Gel	Mechlorethamine-MCH (Nitrogen Mustard) compounded in Aquaphor 0.02%
Measure Participants	130	130
Number [percentage of participants]	76 58.5%	62 47.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PG- Mechlorethamine-MCH (Nitrogen Mustard) 0.02% Gel, AP- Aquaphor Formulation Mechlorethamine-MCH (NM) 0.02%
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The PG formulation was determined to be non-inferior to the AP formulation if the lower limit of the 95% confidence interval around the ratio of the response rates (PG/AP) was > = 0.75.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	ratio of proportions
	Estimated Value	1.226
	Confidence Interval	(2-Sided) 95%; 0.974 to 1.552
	Parameter Dispersion	Type: Value:
	Estimation Comments	ratio is response rate of PG formulation divided by response rate of AP formulation

2. Secondary Outcome

Title	Severity-weighted Assessment Tool (SWAT) Within up to 12 Months by 2 or More Consecutive Observations Over at Least 4 Weeks
Time Frame	Assessment made at Day 1 and every subsequent visit during treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Percent of Participants Achieving at Least 50% Improvement of Severity Weighted Assessment Tool (SWAT)
Description	Assessment of lesion distribution and severity. A responder analysis was performed on whether subject achieved at least 50% improvement on scale. This had to be confirmed on at least one visit at least 4 weeks apart.
Time Frame	Baseline to end of therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PG -Mechlorethamine-MCH (Nitrogen Mustard) 0.02% PG Gel	AP- Mechlorethamine-MCH (NM) 0.02% Compounded in Aquaphor
Arm/Group Description	Study formulation of mechlorethamine-MCH (Nitrogen Mustard) 0.02% Gel	Compounded mechlorethamine-MCH (Nitrogen Mustard) in Aquaphor 0.02%
Measure Participants	130	130
Number [Percent of participants]	61 46.9%	60 46.2%

Adverse Events

Time Frame	adverse event data were collected over 12 months of the patient's participation
Adverse Event Reporting Description	There were a total of 130 participants randomized to each treatment arm. However, 2 from the PG group and 3 from the AP group did not receive drug and are not included in the safety population.
Arm/Group Title	PG -Mechlorethamine-MCH (Nitrogen Mustard) 0.02% PG Gel		AP- Mechlorethamine-MCH (NM) 0.02% Compounded in Aquaphor
Arm/Group Description	Study formulation of mechlorethamine-MCH (Nitrogen Mustard) 0.02% Gel		Compounded mechlorethamine-MCH (Nitrogen Mustard)in Aquaphor 0.02%
All Cause Mortality
	PG -Mechlorethamine-MCH (Nitrogen Mustard) 0.02% PG Gel		AP- Mechlorethamine-MCH (NM) 0.02% Compounded in Aquaphor
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	PG -Mechlorethamine-MCH (Nitrogen Mustard) 0.02% PG Gel		AP- Mechlorethamine-MCH (NM) 0.02% Compounded in Aquaphor
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/128 (0%)		0/127 (0%)
Other (Not Including Serious) Adverse Events
	PG -Mechlorethamine-MCH (Nitrogen Mustard) 0.02% PG Gel		AP- Mechlorethamine-MCH (NM) 0.02% Compounded in Aquaphor
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	108/128 (84.4%)		99/127 (78%)
Infections and infestations
folliculitis	7/128 (5.5%)	7	5/127 (3.9%)	5
Respiratory, thoracic and mediastinal disorders
upper respiratory tract infection	11/128 (8.6%)	11	10/127 (7.9%)	10
Skin and subcutaneous tissue disorders
skin irritation	32/128 (25%)	32	18/127 (14.2%)	18
pruritus	25/128 (19.5%)	25	20/127 (15.7%)	20
erythema	22/128 (17.2%)	22	18/127 (14.2%)	18
dermatitis contact	19/128 (14.8%)	19	19/127 (15%)	19
skin hyperpigmentation	7/128 (5.5%)	7	9/127 (7.1%)	9

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.