Waldenström MacroglobulinemiaPhase 1/2NCT00062244
Oblimersen in Treating Patients With Relapsed or Refractory Waldenstrom's Macroglobulinemia
A Phase 1/2 study testing oblimersen sodium in people with Waldenström Macroglobulinemia, run by National Cancer Institute (NCI) at 8 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Waldenström Macroglobulinemia
- What is being tested?
- oblimersen sodium
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 8 sitesUnited States
- Study dates
- May 2003to Jun 2007
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 59Show fewer
- 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
Who cannot join
None listed.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
University of Maryland Greenebaum Cancer Center
Baltimore, Maryland, 21201-1595
Johns Hopkins University
Baltimore, Maryland, 21287-8936
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, 48201
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792
Mayo Clinic
Rochester, Minnesota, 55905
Mayo Clinic in Arizona
Scottsdale, Arizona, 85259
Howard University Hospital
Washington D.C., District of Columbia, 20060
About this study
Official title: Phase I/II Study of G3139 (Genasense) in Patients With Waldenstrom's Macroglobulinemia
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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.
- Conditions
- Waldenström Macroglobulinemia
- Being tested
- oblimersen sodium
- Medical subject headings
- Waldenstrom Macroglobulinemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
oblimersen sodiumBiological
Also called augmerosen, G3139, G3139 bcl-2 antisense oligodeoxynucleotide, Genasense
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | 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. Receives: Biological: oblimersen sodium |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 21 days
Secondary outcomes (5)
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.
Measured: Up to 2 years
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.
Measured: 6 months
Time to progression
The distribution of time to progression will be estimated using the method of Kaplan-Meier.
Measured: Time from registration to the time of progression, assessed up to 2 years
Overall survival
The distribution of overall survival will be estimated using the method of Kaplan-Meier.
Measured: Time from registration to death due to any cause, assessed up to 2 years
Duration of response
Measured: From the documentation of response until the date of progression, assessed up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2003 (estimated)
- Study startMay 2003
- Primary completionJun 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Waldenström MacroglobulinemiaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Morie Gertz, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00062244
- Sponsor's protocol ID
- NCI-2012-01437
- Other IDs
- MC0285, MAYO-MC0285, NCI-5826, CDR0000304634, N01CM17104
- Status last verified
- Jun 2013
- First submitted
- 5 Jun 2003
- Last updated
- 4 Jun 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of G3139 (Genasense) in Patients With Waldenstrom's Macroglobulinemia
- ClinicalTrials.gov ID
- NCT00062244
- Acronym / sponsor ID
- NCI-2012-01437
- Conditions
- Waldenström Macroglobulinemia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- May 2003
- Primary completion
- Jun 2007 (actual)
- First posted
- 6 Jun 2003 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVES:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Biological: oblimersen sodiumPhase 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (59 listed)
- Diagnosis of Waldenstrom's macroglobulinemia (WM) confirmed by both of the following:
- Symptomatic relapsed or refractory disease requiring therapy, defined by at least 1 of the following:
- 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
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| oblimersen sodiumAlso: augmerosen, G3139, G3139 bcl-2 antisense oligodeoxynucleotide, GenasenseGiven IV | Biological | Arm I |
Primary outcome
Maximum tolerated dose determined by the number of dose-limiting toxicity incidents graded according to CTC standard toxicity (Phase I)
Time frame: 21 days
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.
5 secondary outcomes
Adverse events that are classified as either possibly, probably, or definitely related to study treatment (Phase II)
Time frame: Up to 2 years
Proportion of overall confirmed responses (CR + PR) associated with G3139 (Phase II)
Time frame: 6 months
Time to progression
Time frame: Time from registration to the time of progression, assessed up to 2 years
Overall survival
Time frame: Time from registration to death due to any cause, assessed up to 2 years
Duration of response
Time frame: From the documentation of response until the date of progression, assessed up to 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Morie Gertz principal investigator
Mayo Clinic
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing oblimersen sodium in people with Waldenström Macroglobulinemia, run by National Cancer Institute (NCI) at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 59 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Jun 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose determined by the number of dose-limiting toxicity incidents graded according to CTC standard toxicity (Phase I) (time frame: 21 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2013.