BCX-1777 in Treating Patients With Refractory Cutaneous T-Cell Lymphoma

• ClinicalTrials.gov Identifier: NCT00061880
• Recruitment Status: Completed
• First Posted: June 6, 2003
• Last Update Posted: May 30, 2013
• Sponsor: BioCryst Pharmaceuticals
• Information provided by: National Cancer Institute (NCI)

Study Description

Brief Summary:

RATIONALE: BCX-1777 may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth.

PURPOSE: Phase I/II trial to study the effectiveness BCX-1777 in treating patients who have refractory cutaneous T-cell lymphoma.

Condition or disease	Intervention/treatment	Phase
Lymphoma	Drug: forodesine hydrochloride	Phase 1; Phase 2

Detailed Description:

OBJECTIVES:

• Determine the maximum tolerated dose of BCX-1777 in patients with refractory cutaneous T-cell lymphoma.
• Determine the efficacy of this drug in these patients.
• Determine the toxicity profile of this drug in these patients.
• Correlate plasma concentration of deoxyguanosine with clinical response and toxicity in patients treated with this drug.
• Determine the provisional optimal biological dose of this drug in these patients.

OUTLINE: This is an open-label, nonrandomized, dose-escalation, multicenter study.

• Phase I: Patients receive BCX-1777 IV over 30 minutes every 12 hours on days 1-5 (a total of 9 doses). Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of BCX-1777 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 2 of 6 patients experience dose-limiting toxicity.

• Phase II: Patients receive treatment as in phase I at the MTD of BCX-1777. Patients (including those who respond to treatment) are followed at 14 and 30 days, monthly for 6 months, every 2 months for 6 months, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 3-64 patients (3-24 for phase I and 40 for phase II) will be accrued for this study.

Study Design

• Study Type: Interventional (Clinical Trial)
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 1-2 Multi-Center Study of Intravenous BCX-1777 in Patients With Refractory Cutaneous T-Cell Lymphoma (CTCL)
• Study Start Date: February 2003
• Actual Primary Completion Date: January 2005
• Actual Study Completion Date: January 2008

Arms and Interventions

Outcome Measures

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed cutaneous T-cell lymphoma (CTCL)

  • Any stage except IA patch only

• Previously treated according to 1 of the following:

  • Stage IA plaque, IB, or IIA:

    • At least 4 prior conventional and/or experimental regimens (topical or systemic, including psoralen-ultraviolet light [PUVA] and systemic corticosteroids)

  • Stage IIB, III, or IV:

    • At least 1 prior systemic regimen (systemic corticosteroids and PUVA do not count as systemic regimens for this purpose) NOTE: Repeated use of the same regimen is considered one regimen
• Measurable disease

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-3

Life expectancy

• At least 3 months

Hematopoietic

• Granulocyte count at least 2,000/mm^3
• Platelet count at least 75,000/mm^3
• Hemoglobin at least 10.0 g/dL

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN) (unless due to Gilbert's syndrome)
• ALT no greater than 2 times ULN
• Alkaline phosphatase no greater than 2 times ULN
• No hepatitis B or C

Renal

• Creatinine clearance at least 45 mL/min

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• Human T-cell leukemia virus type 1 (HTLV-1) negative
• No other malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No other illness that would limit study participation
• No active serious infection not controlled by antibiotics

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent anticancer antibody therapy
• No concurrent anticancer immunotherapy
• No concurrent anticancer gene therapy
• No concurrent anticancer vaccine therapy
• No concurrent anticancer angiogenesis inhibitors
• No concurrent sargramostim (GM-CSF)
• No concurrent filgrastim (G-CSF) during course 1 of therapy

Chemotherapy

• More than 21 days since prior chemotherapy unless fully recovered
• No concurrent anticancer chemotherapy

Endocrine therapy

• See Disease Characteristics
• More than 2 weeks since prior topical corticosteroids
• No concurrent anticancer hormonal therapy

Radiotherapy

• More than 2 weeks since prior radiotherapy
• No concurrent radiotherapy

Surgery

• Not specified

Other

• More than 2 weeks since prior antineoplastic therapy
• More than 21 days since prior investigational agents unless fully recovered
• No concurrent citrate-blood products within 30 minutes before or after study treatment
• No concurrent anticancer matrix metalloprotease inhibitors
• No other concurrent anti-CTCL therapy
• No concurrent use of tanning beds
• No other concurrent investigational agents

Contacts and Locations

Locations

United States, Alabama

University of Alabama at Birmingham Comprehensive Cancer Center

Birmingham, Alabama, United States, 35294-3300

United States, North Carolina

Duke Comprehensive Cancer Center

Durham, North Carolina, United States, 27710

United States, Texas

University of Texas - MD Anderson Cancer Center

Houston, Texas, United States, 77030-4009

Sponsors and Collaborators

BioCryst Pharmaceuticals

Investigators

• Study Chair: Alex Shalaurov, MD, PhD; Inveresk Research Group, Incorporated

More Information

• ClinicalTrials.gov Identifier: NCT00061880
• Other Study ID Numbers: BIOCRYST-1777BC-103; CDR0000301763 ( Registry Identifier: PDQ (Physician Data Query) )
• First Posted: June 6, 2003
• Last Update Posted: May 30, 2013
• Last Verified: July 2004

Keywords provided by National Cancer Institute (NCI):

recurrent cutaneous T-cell non-Hodgkin lymphoma; stage I cutaneous T-cell non-Hodgkin lymphoma; stage II cutaneous T-cell non-Hodgkin lymphoma; stage III cutaneous T-cell non-Hodgkin lymphoma; stage IV cutaneous T-cell non-Hodgkin lymphoma; recurrent mycosis fungoides/Sezary syndrome; stage I mycosis fungoides/Sezary syndrome; stage II mycosis fungoides/Sezary syndrome; stage III mycosis fungoides/Sezary syndrome; stage IV mycosis fungoides/Sezary syndrome

Additional relevant MeSH terms:

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