Antibody Therapy in Treating Patients With Refractory or Relapsed Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia

This study has been terminated.
(Medarex (supplier of BsAb) stopped study due to toxicities experienced at other sites on unrelated trials halting manufacturing of BsAb)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier:
NCT00014560
First received: April 10, 2001
Last updated: August 1, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
Leukemia
Lymphoma
Biological: bispecific antibody 4G7xH22
Biological: sargramostim
Phase 1

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Dartmouth-Hitchcock Medical Center:

Primary Outcome Measures:
  • Clinical Toxicity [ Time Frame: day 1-29 ] [ Designated as safety issue: Yes ]
    This study was prematurely ended by the sponsor Medarex (supplier of BsAb) due to toxicities experienced at other sites on unrelated trials leading to the decision that Medarex would not be manufacturing the investigational product (BsAb).

  • Determine the Maximum Tolerated Dose (MTD) and Dose Limiting Toxicity (DLT) of BsAb 4G7 x 22 [ Time Frame: Day 1-29 ] [ Designated as safety issue: Yes ]
    This study was prematurely ended by the sponsor Medarex (supplier of BsAb) due to toxicities experienced at other sites on unrelated trials leading to the decision that Medarex would not be manufacturing the investigational product (BsAb).


Secondary Outcome Measures:
  • Serum Markers of Macrophage Activation [ Time Frame: Day 1 Hours 0,2,4,6,24, day 15 Hours 0,2,4,6,24 ] [ Designated as safety issue: No ]
    This study was prematurely ended by the sponsor Medarex (supplier of BsAb) due to toxicities experienced at other sites on unrelated trials leading to the decision that Medarex would not be manufacturing the investigational product (BsAb).


Enrollment: 3
Study Start Date: September 2000
Estimated Primary Completion Date: February 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single arm
Antibody
Biological: bispecific antibody 4G7xH22 Biological: sargramostim

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00014560

Locations
United States, New Hampshire
Norris Cotton Cancer Center
Lebanon, New Hampshire, United States, 03756-0002
Sponsors and Collaborators
Dartmouth-Hitchcock Medical Center
Investigators
Study Chair: Pamela Ely, MD Norris Cotton Cancer Center
  More Information

No publications provided

Responsible Party: Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier: NCT00014560     History of Changes
Other Study ID Numbers: CDR0000068556, P30CA023108, DMS-9806, NCI-G01-1936
Study First Received: April 10, 2001
Results First Received: April 2, 2013
Last Updated: August 1, 2013
Health Authority: United States: Federal Government

Keywords provided by Dartmouth-Hitchcock Medical Center:
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

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma
Leukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Antibodies
Immunoglobulins
Antibodies, Bispecific
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 30, 2014