CLL
Approved in relapsed CLL in combination with rituximab where rituximab alone is appropriate due to comorbidities

ZYDELIG®
Trial Design

Breakthrough
approval from a
pivotal phase 3 trial

Phase 3 Clinical Study
Design1
Phase 3 clinical study design: randomized combination therapy Phase 3 clinical study design: randomized combination therapy
Rituximab administration:
  • Patients received 8 doses of rituximab: first dose at 375 mg/m2, subsequent doses at 500 mg/m2 for weeks 2, 4, 6, 8, 12, 16, and 20
Clinical endpoint:
  • Primary: progression-free survival as assessed by an independent review committee

First planned interim analysis
was at 50% of events

Key Eligibility Criteria
  Patients with CLL who relapsed within 24 months of their last therapy and required treatment1  
 
Unable to tolerate standard chemoimmunotherapy
  • Coexisting medical conditions (CIRS score ≥6)*
  • OR reduced renal function, defined as CrCl <60 mL/min
  • OR NCI-CTCAE grade ≥3 neutropenia or grade ≥3 thrombocytopenia resulting
    from myelotoxic effects of prior therapy with cytotoxic agents
 
  Prior therapies ≥1 anti-CD20–based regimen or ≥2 prior cytotoxic regimens  

*The CIRS score assesses a patient's comorbidity burden, with higher scores indicating an increased number or increased severity of coexisting illnesses.

CIRS=Cumulative Illness Rating Score; CLL=chronic lymphocytic leukemia; CrCl=creatinine clearance.

Baseline Patient Characteristics1-4
ZYDELIG + R
(n=110)
Rituximab alone
(n=110)
Median age (range), years

Median age (range), years

71 (48-90)
71 (47-92)
Rai stage 0/I-II/III-IV (%)

Rai stage 0/I-II/III-IV (%)

0/31/64
1/26/65
Median Karnofsky performance status

Median Karnofsky performance status

80
80
Unfavorable
genetics (%)

Unfavorable
genetics (%)

Unmutated IGHV
83
85
Del(17p)
24
28
TP53 mutation
38
35
Del(11q)
34
30
Comorbidities and
kidney function

Comorbidities and
kidney function

CIRS score, median (range)
9 (3-18)
8 (1-18)
Total CIRS score >6 (%)
88
82
CrCl, median (range), mL/min
61 (32-161)
67 (21-199)
CrCl <60 mL/min (%)
45
37
Baseline cytopenias,
grade ≥1 (%)

Baseline cytopenias,
grade ≥1 (%)

Anemia
75
72
Neutropenia
34
35
Thrombocytopenia
62
61
Prior regimens, median (range)

Prior regimens, median (range)

3 (1-12)
3 (1-10)
Most common prior regimens (>15%)

Most common prior regimens (>15%)

ZYDELIG + R

BR

46%

FCR

33%

R monotherapy

31%

FR

16%

Clb monotherapy

18%

Rituximab
alone

BR

43%

FCR

36%

R monotherapy

30%

FR

18%

Clb monotherapy

14%

†Cytopenias were defined as blood cell counts below the lower limit of normal. Anemia was defined as a disorder characterized by a reduction in the amount of hemoglobin in 100 mL of blood. Neutropenia was defined as a finding based on laboratory tests that indicate a decrease in the number of neutrophils in the blood specimen. Thrombocytopenia was defined as a finding based on laboratory test results that indicate a decrease in the number of platelets in the blood specimen.5

BR=bendamustine, rituximab; Clb=chlorambucil; FCR=fludarabine, cyclophosphamide, rituximab; FR=fludarabine, rituximab; IGHV=immunoglobulin heavy-chain variable region; R=rituximab.