Oblimersen in Treating Patients With Relapsed or Refractory Waldenstrom's Macroglobulinemia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00062244
First received: June 5, 2003
Last updated: June 3, 2013
Last verified: June 2013
  Purpose

This phase I/II trial is studying the side effects and best dose of oblimersen and to see how well it works in treating patients with relapsed or refractory Waldenstrom's macroglobulinemia. Biological therapies such as oblimersen may interfere with the growth of the cancer cells and slow or stop the growth of Waldenstrom's macroglobulinemia.


Condition Intervention Phase
Waldenström Macroglobulinemia
Biological: oblimersen sodium
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of G3139 (Genasense) in Patients With Waldenstrom's Macroglobulinemia

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum tolerated dose determined by the number of dose-limiting toxicity incidents graded according to CTC standard toxicity (Phase I) [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
    Hematologic dose-limiting toxicity measures will be assessed using the continuous variables as the outcome measures (primarily nadir and percent change from baseline values) as well as categorization.


Secondary Outcome Measures:
  • Adverse events that are classified as either possibly, probably, or definitely related to study treatment (Phase II) [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.

  • Proportion of overall confirmed responses (CR + PR) associated with G3139 (Phase II) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Ninety-five percent confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.

  • Time to progression [ Time Frame: Time from registration to the time of progression, assessed up to 2 years ] [ Designated as safety issue: No ]
    The distribution of time to progression will be estimated using the method of Kaplan-Meier.

  • Overall survival [ Time Frame: Time from registration to death due to any cause, assessed up to 2 years ] [ Designated as safety issue: No ]
    The distribution of overall survival will be estimated using the method of Kaplan-Meier.

  • Duration of response [ Time Frame: From the documentation of response until the date of progression, assessed up to 2 years ] [ Designated as safety issue: No ]

Enrollment: 58
Study Start Date: May 2003
Primary Completion Date: June 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I

Phase I: Patients receive oblimersen IV continuously on days 1-7. Treatment repeats every 3 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 1-6 patients receive escalating doses of oblimersen until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

Phase II: Patients receive treatment as in phase I at the MTD of oblimersen. Patients are followed every 3 months for 2 years.

Biological: oblimersen sodium
Given IV
Other Names:
  • augmerosen
  • G3139
  • G3139 bcl-2 antisense oligodeoxynucleotide
  • Genasense

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the maximally tolerated dose (MTD) and recommended dosing for Genasense in patients with relapsed or refractory WM following prior chemotherapy. (Phase I) II. To determine the response rate to Genasense in patients with relapsed or refractory WM following prior chemotherapy.

III. To determine the safety of Genasense in patients with relapsed or refractory WM following prior chemotherapy.

IV. To describe possible clinical benefit from Genasense treatment of relapsed or refractory WM including duration of response, survival, erythropoietin use, improvement in hemoglobin > 11 g/dl, and Improvement in platelet count > 100,000/mm^3.

OUTLINE: This is a multicenter, dose-escalation study.

Phase I: Patients receive oblimersen IV continuously on days 1-7. Treatment repeats every 3 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 1-6 patients receive escalating doses of oblimersen until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

Phase II: Patients receive treatment as in phase I at the MTD of oblimersen. Patients are followed every 3 months for 2 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of Waldenstrom's macroglobulinemia (WM) confirmed by both of the following:

    • Bone marrow lymphoplasmacytosis with greater than 10% lymphoplasmacytic cells or aggregates, sheets, lymphocytes, plasma cells, or lymphoplasmacytic cells on bone marrow biopsy
    • Measurable disease, defined by quantitative IgM monoclonal protein greater than 1,000 mg/dL
  • Symptomatic relapsed or refractory disease requiring therapy, defined by at least 1 of the following:

    • Impaired bone marrow function due to disease infiltration as demonstrated by any of the following:

      • Hemoglobin less than 11 g/dL
      • Requires epoetin alfa therapy to maintain hemoglobin of at least 11 g/dL
      • Platelet count less than 100,000/mm^3
    • Symptomatic bulky lymphadenopathy
    • Symptoms attributable to hyperviscosity (e.g., nose bleeding, gingival bleeding, or retinal hemorrhage) or serum viscosity level relative to water greater than 4
  • Received at least 1 prior chemotherapy regimen which included chlorambucil, cyclophosphamide, fludarabine, cladribine, or pentostatin
  • No secondary leukemia or history of antecedent hematologic disorder (e.g., myelodysplasia) prior to initial onset of WM
  • Performance status - ECOG 0-2
  • Not specified
  • See Disease Characteristics
  • Absolute neutrophil count at least 1,000/mm^3*
  • Platelet count at least 50,000/mm^3*
  • No bleeding disorder
  • Bilirubin no greater than 2 times upper limit of normal (ULN)
  • AST less than 1.5 times ULN
  • Albumin at least 2.5 g/dL
  • PT no greater than 1.5 times ULN
  • INR no greater than 1.3
  • PTT no greater than 1.5 times ULN
  • No history of chronic hepatitis or cirrhosis
  • Creatinine no greater than 2 times ULN
  • No uncontrolled congestive heart failure
  • No active symptoms of coronary artery disease, including the following:

    • Uncontrolled arrhythmias
    • Recurrent chest pain despite prophylactic medication
  • No New York Heart Association class III or IV heart disease
  • No grade 2 or greater cardiovascular signs and symptoms within the past 4 weeks
  • HIV negative
  • Direct Coombs' test negative
  • No autoimmune thrombocytopenia
  • No uncontrolled serious infection
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Adequate venous access for 7-day continuous infusion of study drug
  • Intellectual, emotional, and physical ability to maintain an ambulatory infusion pump
  • No other cancer except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or other cancer from which the patient has been disease-free for at least 5 years
  • No known hypersensitivity to phosphorothioate-containing oligonucleotides
  • No uncontrolled seizure disorder
  • More than 21 days since prior immunotherapy for WM
  • More than 21 days since prior cytokine, biologic, or vaccine therapy for WM
  • More than 8 weeks since prior plasmapheresis or plasma exchange
  • No prior allogeneic stem cell transplantation
  • No concurrent plasmapheresis or plasma exchange
  • See Disease Characteristics
  • No concurrent corticosteroid therapy
  • More than 21 days since prior radiotherapy for WM
  • More than 21 days since prior major surgery for WM
  • No prior organ allograft
  • Recovered from all prior therapy
  • More than 21 days since other prior therapy for WM
  • No other concurrent investigational therapy
  • No concurrent immunosuppressive drugs
  • No concurrent therapeutic anticoagulation therapy
  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: NCT00062244

Locations
United States, Arizona
Mayo Clinic in Arizona
Scottsdale, Arizona, United States, 85259
United States, District of Columbia
Howard University Hospital
Washington, District of Columbia, United States, 20060
United States, Florida
Mayo Clinic in Florida
Jacksonville, Florida, United States, 32224-9980
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287-8936
University of Maryland Greenebaum Cancer Center
Baltimore, Maryland, United States, 21201-1595
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
Investigators
Principal Investigator: Morie Gertz Mayo Clinic
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00062244     History of Changes
Other Study ID Numbers: NCI-2012-01437, MC0285, MAYO-MC0285, NCI-5826, CDR0000304634, N01CM17104
Study First Received: June 5, 2003
Last Updated: June 3, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Waldenstrom Macroglobulinemia
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Plasma Cell
Paraproteinemias
Vascular Diseases

ClinicalTrials.gov processed this record on October 20, 2014