BCX-1777 in treating patients with refractory cutaneous T-cell lymphoma

Journal of Drugs in Dermatology, August, 2003

Sponsored by: BioCryst Pharmaceuticals

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                     Treatment or          Phase
                              Intervention
recurrent cutaneous
  T-cell lymphoma             Drug: BCX--1777       Phase I
stage I cutaneous             Procedure: enzyme
  T-cell lymphoma               inhibitor therapy   Phase II
stage II cutaneous
  T-cell lymphoma
stage III cutaneous
  T-cell lymphoma
stage IV cutaneous
  T-cell 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

Study Type: Interventional

Study Design: Treatment

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.

* 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.

Ages eligible for study: 18 years and above, both genders

Inclusion Criteria:

* 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:

Performance status

* ECOG 0-3

Life expectancy

* At least 3 months

Hematopoietic

* Granulocyte count at least 2,000/[mm.sup.3]

* Platelet count at least 75,000/[mm.sup.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

* More than 2 weeks since prior topical corticosteroids

* No concurrent anticancer hormonal therapy

Radiotherapy

* More than 2 weeks since prior radiotherapy

* No concurrent radiotherapy

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

Location and Contact Information

Jim Alexander, MD, MPH, Study Chair, Pharma Research Corporation Tuft-New England Medical Center, Boston, Massachusetts, 02111, United State

Massachusetts

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