Phase 3
Completed N=122
Ofatumumab vs Physician's Choice in Subjects With Bulky Fludarabine-Refractory Chronic Lymphocytic Leukemia
Source: ClinicalTrials.gov NCT01313689 ↗Enrolled (actual)
122
Serious AEs
53.8%
Results posted
Nov 2014
Primary outcomePrimary: Progression-free Survival (PFS) as Assessed by Independent Review Committee (IRC) — 5.36; 3.61; 10.05; 7.16 Months — p=0.2677
Summary
The purpose of this study was to confirm the clinical benefit observed in the pivotal registration study, Hx-CD20-406. The Committee for Medicinal Products for Human Use (CHMP) required that a randomized study be conducted in CLL patients with bulky fludarabine-refractory disease as a specific obligation for grant of conditional approval for ARZERRA™ in the European Union (EU). This study compared ofatumumab with the physicians' choice of therapy.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Progression-free Survival (PFS) as Assessed by Independent Review Committee (IRC) |
5.36; 3.61; 10.05; 7.16 | 0.2677 |
| SECONDARY Progression-free Survival (PFS) as Assessed by Investigator |
7.00; 4.50; 12.68; 9.49 | 0.0030 sig |
| SECONDARY Overall Response Rate (ORR) as Assessed by the IRC |
0; 0; 0; 0; 30; 7 | 0.0223 sig |
| SECONDARY Overall Response Rate (ORR) as Assessed by the Investigator |
2; 2; 1; 1; 0; 36 | 0.4159 |
| SECONDARY Overall Survival |
19.19; 14.52; 31.54; 45.50; 8.57 | 0.1732 |
| SECONDARY Time to Progression as Assessed by IRC |
6.31; 5.32; 10.05; 7.16 | — |
| SECONDARY Time to Next Anti-cancer Therapy by Investigator |
11.50; 6.54; 15.47; 9.00 | — |
| SECONDARY Time to Response as Assessed by the IRC |
1.17; 2.56; 1.86; 1.15 | — |
| SECONDARY Duration of Response as Assessed by the IRC |
6.24; 6.95 | — |
| SECONDARY Number of Participants With Any Adverse Event (AE), Any Serious Adverse Event (SAE), Any Fatal Serious Adverse Event (FSAE), or Deaths |
71; 37; 22; 10; 39; 20 | — |
| SECONDARY Number of Participants With Any Adverse Event (AE) of Special Interest |
23; 15; 11; 2; 9; 9 | — |
| SECONDARY Mean Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM Over Time |
0.793; 0.685; 0.807; 1.095; 0.688; 6.909 | — |
| SECONDARY Number of Participants Who Were Positive or Negative for Human Anti-Human Antibodies (HAHA) Post-OFA Therapy |
0; 0; 0; 0; 0; 12 | — |
| SECONDARY Changes From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire, Chronic Lymphocytic Leukaemia 16 Item Module (EORTC QLQ-CLL 16) |
-10.3; -6.3; -9.7; -10.4; -8.5; -6.4 | — |
| SECONDARY Mean Health Change Questionnaire (HCQ) Score |
2.8; 3.9; 2.5; 2.8; 3.2; 3.1 | — |
Eligibility Criteria
Inclusion Criteria
- Adults with documented diagnosis of active CLL requiring treatment
- Bulky lymphadenopathy, defined as at least 1 lymph node >5 cm
- Must be refractory to fludarabine treatment
- Age 18 yrs or older
- At least 2 prior therapies for CLL
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Signed written informed consent
Exclusion Criteria
- Prior allogeneic stem cell transplant at any time, or autologous stem cell transplant within 6 months
- Treatment with any unapproved drug substance or experimental therapy within 4 weeks, or currently participating in another interventional clinical study
- CLL transformation, prolymphocytic leukemia, or central nervous system (CNS) involvement of CLL
- Active autoimmune hemolytic anemia (AIHA) requiring treatment except if associated with progressive disease requiring anti-CLL treatment
- Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment
- Human immunodeficiency virus (HIV) positive
- Significant concurrent, uncontrolled medical condition
- Other past or current malignancy (with the exception of basal cell carcinoma of the skin or in situ carcinoma of the cervix or breast) unless the tumor was successfully treated with curative intent at least 2 years prior to trial entry
- Non-protocol corticosteroid usage except a maintenance dose corresponding to less than or equal to 10 mg prednisone
- Abnormal lab values: Creatinine > 2.0 times upper normal limit (unless normal creatinine clearance), or total bilirubin > 2.0 times upper normal limit (unless due to liver involvement of CLL or due to Gilbert's syndrome), or alanine transaminase (ALT) > 2.5 times upper normal limit (unless due to liver involvement of CLL)
- Known or suspected hypersensitivity to ofatumumab
- Lactating or pregnant women or female patients of child-bearing potential (or male patients with such partners) not willing to use adequate contraception
Data sourced from ClinicalTrials.gov (NCT01313689). 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.