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

Waldenström Macroglobulinemia Clinical Trial

Official title:

Phase I/II Study of G3139 (Genasense) in Patients With Waldenstrom's Macroglobulinemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00062244
• Other study ID #: NCI-2012-01437
• Secondary ID: MC0285MAYO-MC028
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: June 5, 2003
• Last updated: June 3, 2013
• Start date: May 2003

Study information

• Verified date: June 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 58
• Est. primary completion date: June 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Waldenstrom Macroglobulinemia
• Waldenström Macroglobulinemia

Intervention

Biological:
• oblimersen sodium
Given IV

Locations

Country	Name	City	State
United States	Johns Hopkins University	Baltimore	Maryland
United States	University of Maryland Greenebaum Cancer Center	Baltimore	Maryland
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	Mayo Clinic	Rochester	Minnesota
United States	Mayo Clinic in Arizona	Scottsdale	Arizona
United States	Howard University Hospital	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose determined by the number of dose-limiting toxicity incidents graded according to CTC standard toxicity (Phase I)	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.	21 days	Yes
Secondary	Adverse events that are classified as either possibly, probably, or definitely related to study treatment (Phase II)	The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.	Up to 2 years	Yes
Secondary	Proportion of overall confirmed responses (CR + PR) associated with G3139 (Phase II)	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.	6 months	No
Secondary	Time to progression	The distribution of time to progression will be estimated using the method of Kaplan-Meier.	Time from registration to the time of progression, assessed up to 2 years	No
Secondary	Overall survival	The distribution of overall survival will be estimated using the method of Kaplan-Meier.	Time from registration to death due to any cause, assessed up to 2 years	No
Secondary	Duration of response		From the documentation of response until the date of progression, assessed up to 2 years	No