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Study Summary
No. 2008-0841:.......Lymphoma......Alma [Lymphoma - VP Medical Affairs] Rodriguez......Lymphoma/Myeloma
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Study Summary Title
Study Summary
Number:
2008-0841
Study Title:A Single Arm, Safety and Efficacy Study of Ofatumumab in Combination with ICE or DHAP Chemotherapy in Relapsed or Refractory Aggressive Lymphoma Prior to Autologous Stem
Cell Transplantation
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Physician New Patient Referral
Name:Alma [Lymphoma - VP Medical Affairs] RodriguezPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Lymphoma/MyelomaReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-2860
Contact us about clinical trials
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General Information
Disease Group:LymphomaSupported By:GlaxoSmithKline
Phase of Study:Phase IIReturn
Visit:
Patient will need to come to the hospital to have treatment for up to 5 days
every 3 weeks.
Treatment
Agents:
Carboplatin
Chemotherapy
Cisplatin
Cytarabine
Dexamethasone
Etoposide
Ifosfamide
Ofatumumab
Home Care:NA
Treatment Loc:Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions
Estimated
Length of Stay
in Houston:
NA
Description/
Intervention:
The goal of this clinical research is to learn if ofatumumab given in
combination with a routine chemotherapy treatment can help to control the
disease in patients with certain types of lymphoma. Ofatumumab will be studied
in combination with ifosfamide, carboplatin, etoposide (ICE) and in combination
with dexamethasone, cytarabine, and cisplatin (DHAP). The safety of these drug
combinations will also be studied.

At M. D. Anderson, ICE chemotherapy is standard of care. For this reason,
participants at M. D. Anderson will be receiving ofatumumab in combination with
ICE.
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Study Objectives / Outcomes
Primary objective:
  • To evaluate the overall response rate in subjects treated with ofatumumab in combination with either ICE (Ifosfamide, carboplatin, etoposide) or DHAP(Dexamethasone, cytarabine, cisplatin) chemotherapy.

Secondary objectives:
  • To evaluate ofatumumab in combination with either ICE or DHAP chemotherapy with respect to the following:
  • Complete response rate.
  • Ability to mobilize >/= 2x10^6 CD34+ cells/kg from peripheral blood.
  • Safety and tolerability.
  • Ofatumumab pharmacokinetics.
  • Progression-free survival.
  • Overall survival.
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Study Status Information
Study Activation / Registration Date:09/18/2009
IRB Review and Approval Date:09/18/2009
Study Type:Phase Ii Or Phase I/Ii
Recruitment Status:Closed
Projected Accrual:60
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) CD20 positive aggressive NHL including DLBCL, transformed lymphoma & grade 3b FL. If a biopsy or fine needle aspiration (FNA) is performed prior to enrollment to the study it must confirm CD20 positive aggressive lymphoma Note: If evidence emerges that the binding of the immunohistochemical antibody to CD20 can be blocked by rituximab, demonstration of CD20 positivity in the repeat biopsy/FNA will not be required.

2) Refractory to, or relapsed following, first-line treatment with rituximab concurrently with anthracycline- or anthracenedione-based chemotherapy. Relapsed is defined as:confirmed progression after a complete response (CR) duration of >/=28 days. Progression should be confirmed by biopsy or FNA. If neither a biopsy nor FNA is deemed to be appropriate, then the study Principal Investigator may determine eligibility following review of the imaging results and disease history. Subjects must have received rituximab concurrently with at least 6 cycles of chemotherapy.Subjects with stage I/II disease

3) Continuation #2 - will be eligible if they have received rituximab concurrently with at least 3 cycles of chemotherapy and definitive involved-field radiation therapy.Refractory is defined as persistent lymphoma with a partial response (PR), or CR of <28 days duration. Biopsy or FNA reconfirmation of lymphoma is strongly recommended but not mandatory. Subjects must have received rituximab concurrently with at least 6 cycles of chemotherapy. Subjects with stage I/II disease will also be eligible if they received rituximab concurrently with at least 3 cycles of chemotherapy and definitive

4) Continuation #2 - involved-field radiation therapy. Persistent lymphoma and stable disease (SD) after receiving rituximab concurrently with at least 3 cycles of chemotherapy. Biopsy or FNA reconfirmation of lymphoma is recommended but not mandatory. Progressive disease (PD) despite treatment with rituximab combined with chemotherapy. Biopsy or FNA reconfirmation of lymphoma is recommended but not mandatory.

5) Note: Disease response to first-line treatment should be determined according to Revised Response Criteria for Malignant Lymphoma or International Workshop Response criteria for NHL.

6) CT scan showing at least: 2 or more clearly demarcated lesions with a long axis >1.5 cm and short axis >/= 1.0cm. OR 1 clearly demarcated lesion with a long axis >2.0 cm and short axis >/= 1.0cm.

7) Baseline FDG-PET (Positron Emission Tomography) scans must demonstrate positive lesions compatible with CT defined anatomical tumor sites.

8) Age >/=18

9) ECOG ( Eastern Cooperative Oncology Group) performance status 0, 1, or 2.

10) Eligible for high dose chemotherapy and ASCT.

11) Resolution of toxicities from first-line therapy to a grade that in the opinion of the investigator does not contraindicate study participation*.

12) Signed written informed consent.

Exclusion Criteria:1) Any previous cancer therapy this lymphoma, with the exception of: 1) Rituximab in combination with an anthracycline- or anthracenedione-based chemotherapy. 2) Monotherapy rituximab, dosed prior to first-line rituximab combined with chemotherapy, or as maintenance therapy; 3) Radiotherapy as part of the first-line treatment plan; 4) Radiotherapy to a limited field at a maximum dose of </=10Gy to control life threatening symptoms.

2) Received any of the following treatments within 2 weeks prior to start of study therapy (unless otherwise stated): Anti-cancer therapy (e.g. alkylating agents, anti-metabolites, purine analogues); Radiotherapy with the exception of radiotherapy to a limited field at a maximum dose of </=10Gy to control life-threatening symptoms.

3) Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half lives or 4 weeks prior to enrollment, whichever is longer or currently participating in any other interventional clinical study

4) Glucocorticoid therapy in doses >1mg/kg/day prednisolone (or equivalent dose of other glucocorticoid).

5) History of significant cerebrovascular disease or event with significant symptoms or sequelae, unless in the opinion of the investigator it does not contraindicate participation in the study.*

6) Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to enrollment, congestive heart failure (NYHA III-IV), and arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities, unless in the opinion of the investigator it does not contraindicate participation in the study.*

7) Significant concurrent, uncontrolled medical condition, unless in the opinion of the investigator it does not contraindicate participation in this study.*

8) Known or suspected hypersensitivity to study treatments, unless in the opinion of the investigator it does not contraindicate participate in the study.*

9) Known HIV positivity.

10) Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB DNA test will be performed and if positive the subject will be excluded.

11) Active hepatitis C infection.

12) Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis and tuberculosis.

13) Other past or current malignancy unless in the opinion of the investigator it does not contraindicate participation in the study. For example, subjects who have been free of malignancy for at least 5 years, or have a history of completely resected nonmelanoma skin cancer, or successfully treated in situ carcinoma are eligible.*

14) Prior treatment with anti-CD20 monoclonal antibodies, with the exception of rituximab.

15) Screening laboratory values: ICE regimen: platelets <50x10^9/L and neutrophils <1.0 x 10^9/L (unless due to lymphoma involvement of the bone marrow); DHAP regimen: platelets <100x10^9/L and neutrophils <1.5 x 10^9/L (unless due to lymphoma involvement of the bone marrow); measured 12 or 24-hour creatinine clearance of <50mL/min total If a measured creatinine clearance is not available then estimated creatinine clearance is acceptable; total bilirubin >1.5 times upper normal limit in the absence of a known history of Gilbert's disease (unless due to lymphoma involvement of liver)

16) Continuation #15) ALT >2.5 times upper normal limit (unless due to lymphoma involvement of the liver); alkaline phosphatase >2.5 times upper normal limit (unless due to lymphoma involvement of the liver)

17) Subjects known or suspected of being unable to comply with the study protocol.

18) Pregnant or lactating women.

19) Women of childbearing potential, including women whose last menstrual period was less than one year prior to screening, unable or unwilling to use adequate contraception from study start to one year after the last dose of ofatumumab therapy. Adequate contraception is defined as hormonal birth control, intrauterine device, double barrier method or total abstinence. Women of childbearing potential must have a negative pregnancy test prior at screening.

20) Male subjects unable or unwilling to use adequate contraception methods from the time of first dose of study medication until one year after the last dose of ofatumumab.

21) * The GSK Medical Monitor is available to discuss subject eligibility for all criteria.

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Links
Registration Number: NCT00823719
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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