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An Open-label Phase I Drug-drug Interaction Study of Ofatumumab With Bendamustine for the Treatment of Subjects With Indolent B-cell Non-Hodgkin's Lymphoma

Phase 1
18 Years
Not Enrolling

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Trial Information

An Open-label Phase I Drug-drug Interaction Study of Ofatumumab With Bendamustine for the Treatment of Subjects With Indolent B-cell Non-Hodgkin's Lymphoma

The purpose of this study is to evaluate the potential drug-drug interactions between
ofatumumab and bendamustine in subjects with previously untreated or relapsed indolent
B-cell non-Hodgkin's lymphoma (NHL). Ofatumumab and bendamustine will be administered alone
and in combination in a two-arm, open-label study to evaluate the pharmacokinetic profile,
safety, tolerability, and efficacy of ofatumumab and bendamustine.

The primary objective of the study is to evaluate pharmacokinetic parameters of ofatumumab
and bendamustine alone and in combination. Secondary objectives are to evaluate safety,
tolerability, and efficacy.

Inclusion Criteria:

- Subjects with previously untreated or relapsed indolent B-cell NHL requiring
treatment. Indolent NHL is defined as small lymphocytic lymphoma (SLL),
lymphoplasmacytic lymphoma (LPL), marginal zone lymphoma (MZL), and follicular
lymphoma (FL); grades 1, 2, and 3A, defined according to WHO guidelines. Tumor
verified to be CD20+ positive from a previous or current lymph node biopsy.

- At least 4 weeks after previous anti-cancer chemotherapy, or radiotherapy treatment.

- At least 12 weeks after previous anti-CD20 radioimmunotherapy, anti-CD20 antibody
treatment, and non-anti-CD20 monoclonal antibody treatment.

- Subjects who give consent to this study participation and sign the informed consent

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.

- Age greater than or equal to 18 years at informed consent.

- A female subject is eligible to participate if she is of Non-childbearing potential
or required to use a contraception method.

- Male subjects with female partners of child-bearing potential must agree to use a
contraception method.

- Subjects must agree to use contraception until 12 months after the last dose of study

Exclusion Criteria:

- Subjects who failed to achieve a complete remission (CR) or partial remission (PR) or
progressed within 6 months of last rituximab-containing therapy

- Previous treatment with ofatumumab.

- Prior bendamustine treatment not resulting in a complete remission and partial
remission for at least 6 months.

- Previous allogeneic stem cell transplant.

- Previous autologous stem cell transplant.

- High dose steroids greater than or equal to 100 mg prednisone/day (or equivalent) for
greater than or equal to 7 consecutive days, given as concomitant medication, within
3 months prior to randomization. No more than 20 mg prednisone or equivalent daily at
the time of randomization.

- Grade 3b follicular lymphoma or evidence that the indolent lymphoma has transformed
to aggressive lymphoma as verified by biopsy confirmation.

- Known central nervous system involvement by NHL.

- Other past or current malignancy. Subjects who have been free of malignancy for at
least 2 years, or have a history of definitively treated non-melanoma skin cancer, or
successfully treated in situ carcinoma, are eligible.

- Chronic or current active infectious disease requiring systemic antibiotics,
antifungal, or antiviral treatment such as, but not limited to, chronic renal
infection, chronic chest infection with bronchiectasis, tuberculosis, and active
Hepatitis B or C. Prophylactic antibiotics to prevent recurrent of a prior infection
(such as shingles, sinusitis or upper respiratory infection) is allowed.

- Clinically significant cardiac disease as judged by the investigator, including
unstable angina, acute myocardial infarction within 6 months of randomization, and
uncontrolled congestive heart failure (CHF) or arrhythmia. Patients with a history
of CHF or arrhythmia are eligible if their cardiac disease is well controlled on a
stable medical regimen.

- History of significant cerebrovascular disease or event with significant symptoms or
sequelae (as judged by the investigator).

- Significant concurrent, uncontrolled medical condition that in the opinion of the
investigator contraindicates participation this study.

- Positive serology for Hepatitis B (HB) defined as a positive test for Hepatitis B
surface antigen (HBsAg). In addition, if negative for HBsAg but Hepatitis B core
antibody (HBcAb) positive (regardless of Hepatitis B surface antibody [HBsAb]
status), a HB DNA test will be performed and if positive the subject will be
excluded. If HBV DNA is negative, the subject may be included but must undergo
Hepatitis B virus (HBV) DNA monitoring (see Section 7.7.5). Prophylactic antiviral
therapy may be initiated at the discretion of the investigator.

- Current active liver or biliary disease (subjects with Gilbert's syndrome or
asymptomatic gallstones, liver metastases related to indolent NHL or otherwise stable
chronic liver disease per investigator assessment, are eligible).

- Known human immunodeficiency virus (HIV) positive.

- Screening laboratory values:

- platelets < 100 x 109/L (unless due to lymphoma involvement of the bone marrow)

- neutrophils < 1.5 x 109/L (unless due to lymphoma involvement of the bone

- serum creatinine > 1.5 times the institution's upper limit of normal (ULN);
subjects with a serum creatinine > 1.5 ULN will be eligible if the calculated
creatinine clearance [Cockcroft, 1976] or creatinine clearance from a 24-hour
urine collection is ≥ 40 mL/min

- total bilirubin > 1.5 times ULN (unless due to liver involvement by lymphoma or
Gilbert's syndrome)

- transaminases > 2 times ULN

- Known or suspected hypersensitivity to ofatumumab, bendamustine, or mannitol.

- Treatment with any known non-marketed drug substance or experimental therapy within 5
terminal half-lives or 4 weeks prior to Visit 1, whichever is longer or currently
participating in any other interventional clinical study

- Lactating women, women with a positive pregnancy test at Visit 1, or women (of
childbearing potential) as well as men with partners of childbearing potential, who
are not willing to use adequate contraception until 12 months after the last dose of
study drug. Adequate contraception is defined in Section 8.1.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Pharmacokinetic measures of Cmax and Area Under the Curve

Outcome Description:

The amount of ofatumumab and bendamustine in the blood will be measured when given individually or together to obtain Cmax and Area Under the Curve. Bendamustine levels will be collected at Cycles 1 and 2: Predose, 0.25, 0.5, 0.75, 1 (end of infusion), 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, and 24 hours. Ofatumumab will be collected at Cycle 4: Predose, end of infusion, then 1, 2, 24, and 72 hours after end of infusion, then once each on Days 8, 15, and 22.

Outcome Time Frame:

4 months

Safety Issue:


Principal Investigator

GSK Clinical Trials

Investigator Role:

Study Director

Investigator Affiliation:



United States: Food and Drug Administration

Study ID:




Start Date:

November 2012

Completion Date:

April 2015

Related Keywords:

  • Cancer
  • drug-drug interaction
  • Non-Hodgkin's Lymphoma
  • ofatumumab
  • bendamustine
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Lymphoma, B-Cell