Efficacy and Safety Study of PCI-32765 Combine With Ofatumumab in CLL (PCYC-1109-CA)

Pharmacyclics

Status and phase: Completed; Phase 2; Phase 1

Conditions: Prolymphocyctic Leukemia; Richter's Transformation; Small Lymphocytic Lymphoma; B-cell Chronic Lymphocytic Leukemia

Treatments: Drug: ofatumumab; Drug: PCI-32765

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01217749

PCYC-1109-CA

PCI-32765 (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to determine the efficacy and safety of a fixed-dose, daily regimen of orally administered PCI-32765 combined with ofatumumab in subjects with relapsed/refractory CLL/SLL and related diseases

Enrollment: 71 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Subjects with histologically confirmed chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), prolymphocytic leukemia (PLL), or Richter's transformation arising out of CLL/SLL as defined by WHO classification of hematopoietic neoplasms and satisfying ≥ 1 of the following conditions:

   • Progressive splenomegaly and/or lymphadenopathy identified by physical examination or radiographic studies
   • Anemia (<11 g/dL) or thrombocytopenia (<100,000/μL) due to bone marrow involvement
   • Presence of unintentional weight loss > 10% over the preceding 6 months
   • NCI CTCAE Grade 2 or 3 fatigue
   • Fevers > 100.5 degree or night sweats for > 2 weeks without evidence of infection
   • Progressive lymphocytosis with an increase of > 50% over a 2 month period or an anticipated doubling time of < 6 months
   • Need for cytoreduction prior to stem cell transplant

2. Subjects must have failed ≥ 2 prior therapies for CLL including a nucleoside analog or ≥ 2 prior therapies not including nucleoside analog if there is a contraindication to such therapy

3. 10% expression of CD20 on CLL/SLL cells

4. ECOG performance status ≤ 2

5. Life expectancy ≥ 12 weeks

6. Subjects must have organ and marrow function as defined below:

   • Absolute neutrophil count (ANC) ≥ 1000/µL in the absence of bone marrow involvement
   • Platelets ≥ 30,000/μL in the absence of bone marrow involvement
   • Total bilirubin ≤ 1.5 x institutional upper limit of normal unless due to Gilbert's disease
   • AST (SGOT) ≤ 2.5 x institutional upper limit of normal unless due to infiltration of the liver
   • Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 50 mL/min

7. No history of prior exposure to ofatumumab

8. Age ≥ 18 years

9. Body weight ≥ 40 kg

Exclusion criteria

1. A life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of PCI-32765 PO, or put the study outcomes at undue risk
2. Significant cardiovascular disease
3. Any condition which could interfere with the absorption or metabolism of PCI-32765 including unable to swallow capsules, malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction
4. Known history of Human Immunodeficiency Virus (HIV) or active infection with Hepatitis C Virus (HCV) or Hepatitis B Virus (HBV) or any uncontrolled active systemic infection
5. Any anticancer immunotherapy, chemotherapy, radiotherapy, or experimental therapy within 4 weeks before first dose of study drug. Corticosteroids for disease-related symptoms are allowed provided 1 week washout occurs
6. Active central nervous system (CNS) involvement by lymphoma
7. Major surgery within 4 weeks before first dose of study drug
8. Lactating or pregnant
9. Known moderate to severe chronic obstructive pulmonary disease (COPD)
10. History of prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease free for at least 2 years or which will not limit survival to < 2 years
11. History of Grade ≥ 2 toxicity continuing from prior anticancer therapy including radiation

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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71 participants in 3 patient groups

Group 1

Experimental group

Description:

In Group 1, PCI-32765 420 mg PO was administered daily for 1 cycle (28 days) before the start of ofatumumab IV dosing

Treatment:

Drug: PCI-32765

Drug: ofatumumab

Group 2

Experimental group

Description:

In Group 2, PCI-32765 420 mg PO daily was initiated concomitantly with ofatumumab IV (PCI-32765 initiated on Day 2 of Cycle 1)

Treatment:

Drug: PCI-32765

Drug: ofatumumab

Group 3

Experimental group

Description:

In Group 3, two cycles of ofatumumab IV were administered prior to the start of PCI-32765 420 mg PO daily

Treatment:

Drug: PCI-32765

Drug: ofatumumab