Clinical trial NCT00513188: Combination Chemotherapy and Denileukin Diftitox in Treating Patients With Newly Diagnosed T-Cell Non-Hodgkin Lymphoma
Official title: A Pilot Study of the Efficacy of the Chop-Montak Regimen in Patients With Newly Diagnosed Peripheral T Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Lymphoma
Keywords: angioimmunoblastic T-cell lymphoma
anaplastic large cell lymphoma
adult nasal type extranodal NK/T-cell lymphoma
stage IV mycosis fungoides/Sezary syndrome
stage IV cutaneous T-cell non-Hodgkin lymphoma
Lead sponsor: University of Miami
Sponsor class: OTHER
First posted: 2007-08-08
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Combinations of biological substances in denileukin diftitox may be able to carry cancer-killing substances directly to non-Hodgkin lymphoma cells. Giving combination chemotherapy together with denileukin diftitox may kill more cancer cells.

PURPOSE: This clinical trial is studying how well giving combination chemotherapy together with denileukin diftitox works in treating patients with newly diagnosed T-cell non-Hodgkin lymphoma.

Detailed description: OBJECTIVES:

Primary

* To evaluate failure-free survival of patients with newly diagnosed peripheral T-cell non-Hodgkin lymphoma treated with cyclophosphamide, doxorubicin hydrochloride, vincristine, prednisone (CHOP), and denileukin diftitox (Ontak®) alternating with high-dose methotrexate, leucovorin calcium, cytarabine, and Ontak® (CHOP-MONTAK regimen).

Secondary

* To determine the response rate (CR, CRu, and PR) in these patients.
* To determine the overall survival of these patients.
* To determine the toxicity profile of this regimen.
* To correlate response with CD25 expression in these patients.

OUTLINE:

* Courses 1, 3, and 5: Patients receive cyclophosphamide IV over 30 minutes, doxorubicin hydrochloride IV, and vincristine IV on day 1; oral prednisone once daily on days 1-5; and denileukin diftitox IV over 60 minutes on days 1 and 2. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.
* Courses 2, 4, and 6: Patients receive high-dose methotrexate (MTX) IV over 24 hours on day 1; cytarabine IV over 2 hours every 12 hours on days 2 and 3; and leucovorin calcium IV over 15 minutes every 6 hours for 8 doses beginning 12 hours after the last dose of each MTX infusion. Patients also receive denileukin diftitox IV over 60 minutes for 2 doses once MTX blood levels have cleared. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo tumor tissue and blood sample collection periodically for correlative studies. Samples are analyzed for CD25-positive or -negative expression and response rate via flow cytometry.

After completion of study treatment, patients are followed every 3 months for 2 years, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Confirmed diagnosis of peripheral T-cell non-Hodgkin lymphoma

  * Newly diagnosed, previously untreated disease
  * Mycosis fungoides with systemic disease (i.e., beyond the skin) allowed
* No CD30-positive ALK 1-positive T-anaplastic large cell lymphoma
* No skin only involvement
* No localized NK/T-cell lymphoma
* No adult T-cell leukemia/lymphoma
* No known CNS involvement

PATIENT CHARACTERISTICS:

* ECOG performance status 0-2
* Life expectancy \> 3 months
* ANC \> 1,000/mm\^3 (unless due to lymphoma)
* Platelets \> 100,000/mm\^3 (unless due to lymphoma)
* Serum bilirubin ≤ 2.0 mg/dL (unless due to lymphoma)
* Serum creatinine ≤ 1.5 mg/dL (unless due to lymphoma)
* Albumin ≥ 3.0 g/dL
* Cardiac ejection fraction ≥ 50% by MUGA or echocardiogram
* Not pregnant or nursing
* Negative serum or urine β-HCG at screening
* Women and male partners of child-bearing potential must practice an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch) before study entry and throughout the study period
* Willing to receive transfusions of blood products
* No HIV-positive serology
* No uncontrolled intercurrent illness including, but not limited to, any of the following:

  * Ongoing or active infection
  * Symptomatic congestive heart failure
  * Child's class C liver cirrhosis
  * Unstable angina pectoris
  * Cardiac arrhythmia
  * Psychiatric illness or social situations that would limit study compliance
* No other prior or concurrent malignancy with a poor prognosis (i.e., \< 90% probability of survival at 5 years) or that is actively being treated

PRIOR CONCURRENT THERAPY:

* No prior chemotherapy for the treatment of lymphoma
* No other concurrent investigational agents for the treatment of lymphoma

Primary outcomes:
measure: Failure-free survival
Secondary outcomes:
measure: Response rate (CR, CRu, and PR)
measure: Overall survival
measure: Toxicity profile
measure: Correlation of response with CD25 expression
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami Sylvester Comprehensive Cancer Center - Miami
state: Florida
Study officials:
affiliation: University of Miami Sylvester Comprehensive Cancer Center
name: Maricer Escalon, MD, MS
role: STUDY_CHAIR
References: