Clinical trial NCT00014560: Antibody Therapy in Treating Patients With Refractory or Relapsed Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia
Official title: Phase I Trial Of Intravenous Bispecific Antibody (4G7XH22) In Patients With Refractory Or Relapsed Non-Hodgkin's Lymphoma Or Chronic Lymphocytic Leukemia (CLL)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Leukemia
Lymphoma
Keywords: refractory chronic lymphocytic leukemia
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult Burkitt lymphoma
recurrent mantle cell lymphoma
recurrent small lymphocytic lymphoma
Lead sponsor: Dartmouth-Hitchcock Medical Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-07-30
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: 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 antibody therapy in treating patients who have refractory or relapsed non-Hodgkin's lymphoma or chronic lymphocytic leukemia.

Detailed description: OBJECTIVES:

* Determine the maximum tolerated dose and dose-limiting toxicity of bispecific antibody 4G7xH22 in patients with relapsed or refractory non-Hodgkin's lymphoma or chronic lymphocytic leukemia.
* Assess the clinical toxicity of this antibody in these patients.

OUTLINE: This is a dose escalation study of bispecific antibody (BsAb) 4G7xH22.

Patients receive sargramostim (GM-CSF) subcutaneously on day 1 and BsAb 4G7xH22 IV over 2 hours on day 2. Treatment repeats weekly for a total of 3 courses in the absence of unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of BsAb 4G7xH22 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 6 patients experience dose-limiting toxicity.

Patients are followed weekly for 4 weeks, monthly for 3 months, and then periodically for 1 year.

PROJECTED ACCRUAL: Approximately 18 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of CD19+ non-Hodgkin's lymphoma or chronic lymphocytic leukemia

  * Primary refractory or multiply relapsed (after at least 2 prior chemotherapy regimens) disease
  * Ineligible for bone marrow or peripheral blood stem cell transplantation

PATIENT CHARACTERISTICS:

Age:

* Over 18

Performance status:

* ECOG 0-2

Life expectancy:

* More than 3 months

Hematopoietic:

* WBC greater than 3,000/mm\^3
* Platelet count greater than 100,000/mm\^3
* Absolute neutrophil count greater than 1,500/mm\^3

Hepatic:

* Bilirubin less than 1.5 mg/dL
* Alkaline phosphatase less than 2 times normal
* SGPT less than 2 times normal

Renal:

* Creatinine clearance greater than 50 mL/min

Other:

* No human-anti-murine-antibody response to prior murine monoclonal antibodies
* No immunological or inflammatory disease (e.g., lupus erythematosus)
* No active serious infection
* No other serious medical condition that would limit survival to less than 2 years
* No other active malignancy except non-melanoma skin cancer or carcinoma in situ of the cervix
* No psychiatric or addictive disorder that would preclude study
* Not pregnant or nursing
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Prior immunotherapy allowed

Chemotherapy:

* See Disease Characteristics
* No concurrent chemotherapy

Endocrine therapy:

* Concurrent steroids for adrenal failure or adverse reactions to study drug allowed
* Concurrent hormonal therapy for non-disease related conditions (e.g., insulin for diabetes) allowed

Radiotherapy:

* Not specified

Surgery:

* Not specified

Primary outcomes:
measure: Clinical Toxicity
timeFrame: day 1-29
measure: Determine the Maximum Tolerated Dose (MTD) and Dose Limiting Toxicity (DLT) of BsAb 4G7 x 22
timeFrame: Day 1-29
Secondary outcomes:
measure: Serum Markers of Macrophage Activation
timeFrame: Day 1 Hours 0,2,4,6,24, day 15 Hours 0,2,4,6,24
Other outcomes:
Locations:
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center
state: New Hampshire
Study officials:
affiliation: Norris Cotton Cancer Center
name: Pamela Ely, MD
role: STUDY_CHAIR
References: