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Investigator Initiated Pilot Study of Microarray Directed Therapy for Diffuse Large B-cell Lymphoma Using Genasense With CHOP-R


N/A
19 Years
N/A
Not Enrolling
Both
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

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Trial Information

Investigator Initiated Pilot Study of Microarray Directed Therapy for Diffuse Large B-cell Lymphoma Using Genasense With CHOP-R


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.


Inclusion Criteria:



- 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)

- 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

Exclusion Criteria:

- 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

- 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

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Feasibility of performing an AFFYmetrix microarray study

Outcome Time Frame:

Within 7 working days of receipt of adequate tissue samples at the University of Nebraska Medical Center (UNMC)

Safety Issue:

No

Principal Investigator

Julie Vose

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Nebraska

Authority:

United States: Food and Drug Administration

Study ID:

462-07

NCT ID:

NCT00736450

Start Date:

July 2008

Completion Date:

October 2022

Related Keywords:

  • 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
  • Lymphoma
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Lymphoma, B-Cell

Name

Location

UNMC Eppley Cancer Center at the University of Nebraska Medical CenterOmaha, Nebraska  68198-7680
Saint Francis Medical CenterGrand Island, Nebraska  68802