Contiguous Stage II Adult Diffuse Large Cell LymphomaEarly Phase 1NCT00736450
Oblimersen Sodium & Combination Chemotherapy in Treating Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma
A Early Phase 1 study testing oblimersen sodium, rituximab and cyclophosphamide in people with Contiguous Stage II Adult Diffuse Large Cell Lymphoma and Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma, run by University of Nebraska at 2 sites in United States.
Trial summary
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Oblimersen sodium may help chemotherapy work better by making cancer cells more sensitive to the drugs. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Contiguous Stage II Adult Diffuse Large Cell Lymphoma, Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma, Stage I Adult Diffuse Large Cell Lymphoma
- What is being tested?
- oblimersen sodium, rituximab and cyclophosphamide
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 2 sitesUnited States
- Study dates
- 23 Jul 2008to 9 Oct 2012
- Phase
- Early Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Newly diagnosed patients with Diffuse Large B-cell Lymphoma (DLBCL) (any stage) OR composite lymphoma with >= 50% DLBCL
- Adequate diagnostic tissue for microarray gene expression analysis or IHC analysis
- Karnofsky Performance Status >= 70 (ECOG 0, 1)
- No prior chemotherapy (with the exception of 1 cycle CHOP-R based on current diagnosis, clinical condition, and availability/feasibility of initiating Genasense), immunotherapy, radiotherapy, or investigational therapies for NHL; steroid therapy is allowed only if required for maintenance of another chronic disease (e.g., rheumatoid arthritis)
- Patients aged >= 60 years, or patients with a history of coronary artery disease, congestive heart failure, hypertension, diabetes, or hyperlipidemia must have an estimated ejection fraction >= 0.45 (45%) by MUGA or echocardiography, performed within two months of study entry
- Patients must be willing to give written informed consent, and sign an institutionally approved consent form prior to initiating genasense or any study related activities (i.e., Genasense \& microarray)
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- Females of childbearing potential must have a negative serum pregnancy test prior to enrollment in the study
- Adequate venous access for 7-day continuous infusion
- Patients without evidence of severe organ dysfunction as determined within two weeks of 1st cycle of CHOP-R: 1) Hemoglobin > 8 g/dl; 2) Absolute neutrophil count > 1000/; 3) Platelets > 100,000 (lower blood counts may be acceptable if due to lymphoma after review with principal investigator); 4) Creatinine =< 2.0 mg/dL (unless due to NHL); 5) Bilirubin =< 2.0 mg/dL; 6) AST =< 3 x upper normal; 7) ALP =< 3 x upper normal (unless due to NHL)
- Men and women of reproductive potential must agree to use TWO of the following forms of birth control every time they have sex throughout the study and for up to 3 months following discontinuation of study drug: hormonal birth control methods, condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicidal, IUD, or surgical sterilization while participating in this study
Who cannot join
- Significant medical disease other than cancer including: 1) Any bleeding or coagulation disorder including a history of autoimmune hemolytic anemia or autoimmune thrombocytopenia; 2) Severe pulmonary disease; 3) Uncontrolled congestive heart failure; 4) New York Heart Association class III or IV disease; 5) Uncontrolled seizure disorder; and 6) Active infections
- Less than 3 weeks from prior major surgery
- Prior organ allograft
- Known HIV infection (due to expected frequent occurrence of myelo-suppression and immunosuppression)
- Women who are pregnant (confirmed by a serum pregnancy test in females of reproductive potential) or breast-feeding (women of child-bearing potential and sexually active males must be advised to take precautions to prevent pregnancy during treatment or remain abstinent)
- Women of child-bearing potential and sexually active males must be advised to take precautions to prevent pregnancy during treatment (unless the subject or subject's partner(s) is sterile, i.e., women who have had a hysterectomy or have been post-menopausal for at least twelve consecutive months) or remain abstinent
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- Known hypersensitivity to phosphorothiate-containing oligonucleotides
- Concurrent investigational, corticosteroid therapy or any other anti-cancer treatments (such as chemotherapy, radiation, biologic or investigational therapies) while receiving protocol therapy; other than one cycle CHOP-R allowed based on current diagnosis, clinical condition, and availability/feasibility of initiating Genasense; other than chronic steroid use for another indication (For stage I/II or as clinically indicated- involved field irradiation as per standard practice is accepted)
- Other investigational drug therapy within 30 days of study entry
- Secondary leukemia or history of antecedent hematologic disorder
- History of second cancer (except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for three or more years)
- No active CNS disease defined as symptomatic meningeal lymphoma or known CNS parenchymal lymphoma
- Concomitant anticoagulant therapy is not permitted (with the exception of 1 mg/day of warfarin for central line prophylaxis)
- Known hypersensitivity to G3139 (Genasense) or R-CHOP
- Neurologic disorders, overt psychosis, mental disability or evidence of limited capacity to provide fully informed consent or cooperation with the complexities of the treatment program
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Saint Francis Medical Center
Grand Island, Nebraska, 68803
University of Nebraska Medical Center
Omaha, Nebraska, 68198-6805
About this study
Official title: Investigator Initiated Pilot Study of Microarray Directed Therapy for Diffuse Large B-cell Lymphoma Using Genasense With CHOP-R
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Oblimersen sodium may help chemotherapy work better by making cancer cells more sensitive to the drugs. Giving oblimersen sodium together with combination chemotherapy may kill more cancer cells. PURPOSE: This clinical trial is studying the side effects of giving oblimersen sodium together with combination chemotherapy and to see how well it works in treating patients with newly diagnosed stage I, stage II, stage III, or stage IV diffuse large B-cell lymphoma
Read the detailed description
PRIMARY OBJECTIVES: I. To assess the feasibility and determine the rate of rapid turn around, that is within 7 working days of receipt of adequate tissue at UNMC for a AFFYmetrix microarray study of newly diagnosed patients with Diffuse Large B-cell Lymphoma (DLBCL) who will then receive treatment on this protocol. II. To evaluate efficacy (complete response rate) of Genasense (antisense bcl-2) given in addition to standard cyclophosphamide, vincristine, doxorubicin, and prednisone -rituximab (CHOP-R) to newly diagnosed patients with DLBCL who are found to have the ABC type after gene expression profiling or IHC as compared to newly diagnosed patients with DLBCL who do not express the ABC type that go on to receive standard CHOP-R (control). III. To evaluate the toxicity of Genasense (antisense bcl-2) given in addition to standard cyclophosphamide, vincristine, doxorubicin, and prednisone -rituximab (CHOP-R) for newly diagnosed patients with DLBCL who are found to have the ABC type after gene expression profiling. OUTLINE: Patients with diffuse large B-cell lymphoma (DLBCL) that expresses ABC type proceed to treatment in group I. Patients with DLBCL that does not express ABC type proceed to treatment in group II. GROUP I (oblimersen sodium and standard CHOP-R): Patients receive oblimersen sodium IV continuously on days 1-7. Patients also receive CHOP-R comprising rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 5 and prednisone orally on days 5-10. Treatment repeats every 3 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity. GROUP II (standard CHOP-R alone): Patients receive CHOP-R comprising rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 1 and prednisone orally on days 1-5. Treatment repeats every 3 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed periodically.
- Conditions
- Contiguous Stage II Adult Diffuse Large Cell Lymphoma, Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma, Stage I Adult Diffuse Large Cell Lymphoma, Stage III Adult Diffuse Large Cell Lymphoma, Stage IV Adult Diffuse Large Cell Lymphoma
- Being tested
- oblimersen sodium, rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse
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
rituximabBiological
Also called IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8
Given IV
cyclophosphamideDrug
Also called CPM, CTX, Cytoxan, Endoxan
Given IV
Also called ADM, ADR, Adria, Adriamycin PFS
Given IV
Also called leurocristine sulfate, VCR, Vincasar PFS
Given IV
prednisoneDrug
Also called DeCortin, Deltra
Given orally
biopsyProcedure or surgery
Also called biopsies
Correlative studies
microarray analysisGenetic
Also called gene expression profiling
Correlative studies
immunohistochemistry staining methodOther
Also called immunohistochemistry
Correlative studies
gene expression analysisGenetic
Correlative studies
cytogenetic analysisGenetic
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | See Detailed Description Receives: Biological: oblimersen sodium; Biological: rituximab; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: vincristine sulfate; Drug: prednisone; Procedure: biopsy; Genetic: microarray analysis; Other: immunohistochemistry staining method; Genetic: gene expression analysis; Genetic: cytogenetic analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Perform Microarray Study After Receipt of Tissue
The time from tissue harvest to release of microarray test and IHC assay results will be noted in days.
Measured: Upto 14 days
Number of Participants With Microarray Testing Results Are Completed Within 7 Days.
Measured: Upto 7 days
Secondary outcomes (1)
Efficacy of Treatment, in Terms of Complete Response Rate (Anyone Achieving a CR or Cru)
Response criteria are the recommendations of the International Harmonization Project's update to the International Working Group guidelines. Complete response (CR) is defined as disappearance of all evidence of disease; Partial response (PR) is defined as regression of measurable disease and no new sites
Measured: End of treatment, an average of 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2008 (estimated)
- Study start23 Jul 2008
- Primary completion9 Oct 2012
- Study completion9 Oct 2012
Why it stopped: Manufacturer is no longer making the drug.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Contiguous Stage II Adult Diffuse Large Cell LymphomaStudies of the same condition, open and under way.
- More trials run by University of NebraskaThe 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Nebraska
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Genta Incorporated
- Responsible party
- Sponsor
- Investigators
- Julie M Vose, MD MBA, Principal investigator, University of Nebraska
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00736450
- Sponsor's protocol ID
- 0462-07-FB
- Other IDs
- NCI-2009-01692, P30CA036727
- Status last verified
- Oct 2023
- First submitted
- 14 Aug 2008
- Last updated
- 24 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigator Initiated Pilot Study of Microarray Directed Therapy for Diffuse Large B-cell Lymphoma Using Genasense With CHOP-R
- ClinicalTrials.gov ID
- NCT00736450
- Acronym / sponsor ID
- 0462-07-FB
- Conditions
- Contiguous Stage II Adult Diffuse Large Cell Lymphoma, Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma, Stage I Adult Diffuse Large Cell Lymphoma, Stage III Adult Diffuse Large Cell Lymphoma, Stage IV Adult Diffuse Large Cell Lymphoma
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Manufacturer is no longer making the drug.
- Enrolment
- 37 participants (actual)
- Lead sponsor
- University of NebraskaUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Genta Incorporated
- Study start
- 23 Jul 2008 (actual)
- Primary completion
- 9 Oct 2012 (actual)
- Study completion
- 9 Oct 2012 (actual)
- First posted
- 15 Aug 2008 (estimated)
- Results
- Posted 31 Aug 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Oblimersen sodium may help chemotherapy work better by making cancer cells more sensitive to the drugs. Giving oblimersen sodium together with combination chemotherapy may kill more cancer cells. PURPOSE: This clinical trial is studying the side effects of giving oblimersen sodium together with combination chemotherapy and to see how well it works in treating patients with newly diagnosed stage I, stage II, stage III, or stage IV diffuse large B-cell lymphoma
Detailed description
PRIMARY OBJECTIVES: I. To assess the feasibility and determine the rate of rapid turn around, that is within 7 working days of receipt of adequate tissue at UNMC for a AFFYmetrix microarray study of newly diagnosed patients with Diffuse Large B-cell Lymphoma (DLBCL) who will then receive treatment on this protocol. II. To evaluate efficacy (complete response rate) of Genasense (antisense bcl-2) given in addition to standard cyclophosphamide, vincristine, doxorubicin, and prednisone -rituximab (CHOP-R) to newly diagnosed patients with DLBCL who are found to have the ABC type after gene expression profiling or IHC as compared to newly diagnosed patients with DLBCL who do not express the ABC type that go on to receive standard CHOP-R (control). III. To evaluate the toxicity of Genasense (antisense bcl-2) given in addition to standard cyclophosphamide, vincristine, doxorubicin, and prednisone -rituximab (CHOP-R) for newly diagnosed patients with DLBCL who are found to have the ABC type after gene expression profiling. OUTLINE: Patients with diffuse large B-cell lymphoma (DLBCL) that expresses ABC type proceed to treatment in group I. Patients with DLBCL that does not express ABC type proceed to treatment in group II. GROUP I (oblimersen sodium and standard CHOP-R): Patients receive oblimersen sodium IV continuously on days 1-7. Patients also receive CHOP-R comprising rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 5 and prednisone orally on days 5-10. Treatment repeats every 3 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity. GROUP II (standard CHOP-R alone): Patients receive CHOP-R comprising rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 1 and prednisone orally on days 1-5. Treatment repeats every 3 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed periodically.
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 sodium, Biological: rituximab, Drug: cyclophosphamide, Drug: doxorubicin hydrochloride, Drug: vincristine sulfate, Drug: prednisone, Procedure: biopsy, Genetic: microarray analysis, Other: immunohistochemistry staining method, Genetic: gene expression analysis, Genetic: cytogenetic analysisSee Detailed Description |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Newly diagnosed patients with Diffuse Large B-cell Lymphoma (DLBCL) (any stage) OR composite lymphoma with >= 50% DLBCL
- Adequate diagnostic tissue for microarray gene expression analysis or IHC analysis
- Karnofsky Performance Status >= 70 (ECOG 0, 1)
- No prior chemotherapy (with the exception of 1 cycle CHOP-R based on current diagnosis, clinical condition, and availability/feasibility of initiating Genasense), immunotherapy, radiotherapy, or investigational therapies for NHL; steroid therapy is allowed only if required for maintenance of another chronic disease (e.g., rheumatoid arthritis)
- Patients aged >= 60 years, or patients with a history of coronary artery disease, congestive heart failure, hypertension, diabetes, or hyperlipidemia must have an estimated ejection fraction >= 0.45 (45%) by MUGA or echocardiography, performed within two months of study entry
Key exclusion criteria (15 listed)
- Significant medical disease other than cancer including: 1) Any bleeding or coagulation disorder including a history of autoimmune hemolytic anemia or autoimmune thrombocytopenia; 2) Severe pulmonary disease; 3) Uncontrolled congestive heart failure; 4) New York Heart Association class III or IV disease; 5) Uncontrolled seizure disorder; and 6) Active infections
- Less than 3 weeks from prior major surgery
- Prior organ allograft
- Known HIV infection (due to expected frequent occurrence of myelo-suppression and immunosuppression)
- Women who are pregnant (confirmed by a serum pregnancy test in females of reproductive potential) or breast-feeding (women of child-bearing potential and sexually active males must be advised to take precautions to prevent pregnancy during treatment or remain abstinent)
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 |
| rituximabAlso: IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8Given IV | Biological | Arm I |
| cyclophosphamideAlso: CPM, CTX, Cytoxan, EndoxanGiven IV | Drug | Arm I |
| doxorubicin hydrochlorideAlso: ADM, ADR, Adria, Adriamycin PFSGiven IV | Drug | Arm I |
| vincristine sulfateAlso: leurocristine sulfate, VCR, Vincasar PFSGiven IV | Drug | Arm I |
| prednisoneAlso: DeCortin, DeltraGiven orally | Drug | Arm I |
| biopsyAlso: biopsiesCorrelative studies | Procedure or surgery | Arm I |
| microarray analysisAlso: gene expression profilingCorrelative studies | Genetic | Arm I |
| immunohistochemistry staining methodAlso: immunohistochemistryCorrelative studies | Other | Arm I |
| gene expression analysisCorrelative studies | Genetic | Arm I |
| cytogenetic analysisCorrelative studies | Genetic | Arm I |
Primary outcome
Time to Perform Microarray Study After Receipt of Tissue
Time frame: Upto 14 days
The time from tissue harvest to release of microarray test and IHC assay results will be noted in days.
Number of Participants With Microarray Testing Results Are Completed Within 7 Days.
Time frame: Upto 7 days
1 secondary outcome
Efficacy of Treatment, in Terms of Complete Response Rate (Anyone Achieving a CR or Cru)
Time frame: End of treatment, an average of 4 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Julie M Vose, MD MBA principal investigator
University of Nebraska
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing oblimersen sodium, rituximab and cyclophosphamide in people with Contiguous Stage II Adult Diffuse Large Cell Lymphoma and Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma, run by University of Nebraska at 2 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 10 inclusion and 15 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: stopped early, as of the sponsor's last update on 24 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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 phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Aug 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Time to Perform Microarray Study After Receipt of Tissue (time frame: Upto 14 days). The study lists 2 primary outcomes in all. 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 24 Oct 2023.