Phase 2
Completed N=61
Phase II Study of Ofatumumab Plus Ifosfamide, Carboplatin, Etoposide (ICE) or Dexamethasone, Cytarabine, Cisplatin (DHAP) Chemotherapy Regimen in Relapsed/ Refractory Diffuse Large B Cell Lymphoma (DLBCL)
Source: ClinicalTrials.gov NCT00823719 ↗Enrolled (actual)
61
Serious AEs
39.3%
Results posted
Sep 2012
Primary outcomePrimary: Number of Participants With Overall Response (OR), as Assessed by the Investigator — 18; 18; 36 participants
Summary
The purpose of this study is to evaluate the safety and efficacy of ofatumumab used in combination with ifosfamide, carboplatin, etoposide (ICE) or dexamethasone, cytarabine, cisplatin (DHAP) salvage chemotherapy regimens in subjects with relapsed or refractory diffuse large B cell lymphoma (DLBCL) who are eligible for autologous stem cell transplant.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Overall Response (OR), as Assessed by the Investigator |
18; 18; 36 | — |
| SECONDARY Number of Participants With CR, as Assessed by the Investigator |
11; 11; 22 | — |
| SECONDARY Number of Participants With the Ability to Mobilize at Least 2 Million Cluster of Differentiation (CD)34+ Cells Per Kilogram (kg) From Peripheral Blood |
23; 20; 43 | — |
| SECONDARY Progression-free Survival (PFS) |
301.0; 288.0; 288.0 | — |
| SECONDARY Overall Survival |
433.0; NA; 508.0 | — |
| SECONDARY Area Under the Concentration-time Curve From Time Zero to Infinity, AUC(0-inf), of Ofatumumab at the First Infusion (Cycle 1, Day 1) and the Last Infusion (Cycle 3) |
34056; 33606; 33691; 115741; 105898; 111203 | — |
| SECONDARY Area Under the Concentration-time Curve During the Dosing Interval (AUC(0-tau)) of Ofatumumab at the Last Infusion (Cycle 3) |
95112; 83385; 87891; 112676; 95341; 101948 | — |
| SECONDARY Clearance (CL) of Ofatumumab |
8.7; 9.2; 9.0 | — |
| SECONDARY Maximum Plasma Concentration (Cmax) of Ofatumumab at the First Infusion (Cycle 1 Day 1), Second Infusion (Cycle 1 Day 8), and Last Infusion (Cycle 3) |
89.8; 80.0; 81.8; 323; 268; 297 | — |
| SECONDARY Trough Plasma Concentration (Ctrough) of Ofatumumab Prior to Second Infusion (Cycle 1 Day 8), Third Infusion (Cycle 2), and Last Infusion (Cycle 3) |
31.8; 28.3; 29.1; 95.8; 106; 101 | — |
| SECONDARY Terminal Phase Half-life (t1/2) of Ofatumumab |
595; 646; 624 | — |
| SECONDARY Volume of Distribution at Steady State (Vss) of Ofatumumab |
7.12; 8.13; 7.68 | — |
| SECONDARY Number of Participants Who Were Positive and Negative for Human Anti-human Antibodies (HAHA) at the Indicated Time Points |
0; 0; 0; 26; 35; 61 | — |
| SECONDARY Number of Participants With the Indicated Adverse Events (AEs) Associated With Neutropenia |
12; 11; 23; 7; 11; 18 | — |
| SECONDARY Number of Participants With the Indicated AEs Associated With Decreased Hemoglobin Counts |
16; 18; 34; 14; 16; 30 | — |
| SECONDARY Number of Participants With the Indicated AEs Associated With Decreased Platelet Counts |
21; 19; 40; 20; 19; 39 | — |
Eligibility Criteria
Inclusion Criteria
- Subjects with CD20 positive aggressive non-Hodgkin's lymphoma (NHL) including DLBCL, transformed follicular lymphoma (FL) & grade 3b FL.
Refractory to, or relapsed following, first-line treatment with rituximab combined with anthracycline- or anthracenedione-based chemotherapy as defined by the protocol.
- Computed tomography (CT) with involvement of 2 or more clearly demarcated lesions with a long axis > 1.5 centimeters (cm) and short axis ≥ 1.0 cm or 1 clearly demarcated lesion with a long axis >2.0 cm and short axis ≥1.0 cm.
- Baseline [18F] fluorodeoxyglucose (FDG)-positron emission tomography (PET) scans must demonstrate positive lesions compatible with CT defined anatomical tumor sites.
- Age 18 yrs or older.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
- Eligible for high dose chemotherapy and autologous stem cell transplant (ASCT).
- Resolution of toxicities from first-line therapy to a grade that in the opinion of the investigator does not contraindicate study participation.
- Signed written informed consent.
Exclusion Criteria
- Previous cancer therapy for lymphoma, with the exception of required rituximab/ anthracycline- or anthracenedione-based chemotherapy, monotherapy rituximab prior to first-line therapy and / or as a maintenance therapy, or limited field radiotherapy (as defined by the protocol).
- Any anti-cancer therapy, except limited field radiotherapy, within 2 weeks prior to start of study therapy.
- Chronic Glucocorticoid use (limited acute use is allowed and defined by the protocol).
- History of significant cerebrovascular disease.
- Abnormal/ inadequate white blood cell (WBC) count, liver, and kidney function.
- Clinically significant cardiac disease, active or chronic infections, serious significant diseases, other cancer within last 5 years.
- Known or suspected hypersensitivity to study treatments.
- Prior treatment with anti-CD20 monoclonal antibodies, at any time, or treated with other monoclonal antibodies within 3 months prior to start of study therapy, with the exception of rituximab in both instances.
- Inability to comply with the protocol activities.
- Pregnant or lactating women or female patients of child-bearing potential (or male patients with such partners) not willing to use adequate contraception during and up to 1 year following dosing completion.
Data sourced from ClinicalTrials.gov (NCT00823719). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.