Clinical trial NCT00006009: Monoclonal Antibody Therapy in Treating Patients With Advanced or Recurrent Lymphoma
Official title: A Phase I, Multiple Dose Escalation Trial of Intravenous Humanized Anti-CD3 Antibody (HuM291) in Patients With CD3+ T-cell Lymphomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lymphoma
Small Intestine Cancer
Keywords: 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 cutaneous T-cell non-Hodgkin lymphoma
small intestine lymphoma
stage III adult T-cell leukemia/lymphoma
stage IV adult T-cell leukemia/lymphoma
recurrent adult T-cell leukemia/lymphoma
angioimmunoblastic T-cell lymphoma
anaplastic large cell lymphoma
stage I mycosis fungoides/Sezary syndrome
stage II mycosis fungoides/Sezary syndrome
stage III mycosis fungoides/Sezary syndrome
stage IV mycosis fungoides/Sezary syndrome
recurrent mycosis fungoides/Sezary syndrome
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-10-08
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

PURPOSE: Phase I trial to study the effectiveness of monoclonal antibody therapy in treating patients who have advanced or recurrent lymphoma.

Detailed description: OBJECTIVES:

* Determine the safety and tolerability of monoclonal antibody HuM291 in patients with advanced or recurrent CD3+ T-cell lymphomas.
* Evaluate the pharmacokinetics and pharmacodynamics of this treatment regimen in this patient population.
* Determine the response in these patients treated with this regimen.

OUTLINE: This is a dose-escalation study.

Patients receive monoclonal antibody HuM291 IV over 3 hours on days 1-4 in the absence of unacceptable toxicity. Patients achieving a partial response, complete response with recurrence, or stable disease may receive further therapy.

Cohorts of 3-6 patients receive escalating doses of monoclonal antibody HuM291 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 6 patients experience dose-limiting toxicity.

Patients are followed weekly for 1 month and then monthly for 3 months.

PROJECTED ACCRUAL: A total of 12-15 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed CD3+ T-cell lymphoma for which no standard curative therapy exists

  * Peripheral T-cell lymphoma

    * Recurrent and/or progressive disease after at least 1 prior therapy
  * Mycosis fungoides

    * Stage IB/IIA

      * Recurrent and/or progressive disease after at least 2 prior therapies
    * Stage IIB-IVB

      * Recurrent and/or progressive disease after at least 1 prior therapy
  * All other T-cell lymphomas

    * Recurrent and/or progressive disease after at least 1 prior therapy
* Evaluable disease

  * Any nodal site or mass lesion at least 1.5 cm in longest axis on physical exam or CT scan
  * Skin lesions at least 1 cm in longest axis for cutaneous lymphoma
* High numbers of circulating T-cells allowed

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* ECOG 0-2
* Karnofsky 50-100%

Life expectancy:

* Not specified

Hematopoietic:

* WBC at least 2,000/mm\^3\*
* Absolute neutrophil count at least 1,000/mm\^3\*
* Platelet count at least 75,000/mm\^3\* NOTE: \* Unless due to lymphoma

Hepatic:

* Bilirubin no greater than 2.0 times normal\*
* AST/ALT no greater than 2.5 times upper limit of normal\*
* Hepatitis B and C negative NOTE: \* Unless due to lymphoma

Renal:

* Not specified

Cardiovascular:

* No symptomatic congestive heart failure
* No unstable angina pectoris
* No cardiac arrhythmia

Other:

* No other uncontrolled illness
* No ongoing or active infection
* No other active malignancies except basal cell skin cancer or carcinoma in situ of the cervix
* HIV-1 negative
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics

Biologic therapy:

* At least 60 days since prior humanized or chimeric antibody therapy

Chemotherapy:

* At least 3 weeks since prior chemotherapy

Endocrine therapy:

* Not specified

Radiotherapy:

* At least 3 weeks since prior radiotherapy

Surgery:

* Not specified

Other:

* At least 30 days since prior investigational drugs or therapies

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
Study officials:
affiliation: Stanford University
name: Youn H. Kim, MD
role: STUDY_CHAIR
References: