Efficacy and Safety Study of PCI-32765 Combine With Ofatumumab in CLL

NCT ID: NCT01217749

Last Updated: 2015-06-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 71 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-12-31
• Study Completion Date: 2014-05-31

Brief Summary

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

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group 1

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

Group Type: EXPERIMENTAL

PCI-32765

Intervention Type: DRUG

420 mg PO daily

ofatumumab

Intervention Type: DRUG

per package insert as an IV infusion

Group 2

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

Group Type: EXPERIMENTAL

PCI-32765

Intervention Type: DRUG

420 mg PO daily

ofatumumab

Intervention Type: DRUG

per package insert as an IV infusion

Group 3

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

Group Type: EXPERIMENTAL

PCI-32765

Intervention Type: DRUG

420 mg PO daily

ofatumumab

Intervention Type: DRUG

per package insert as an IV infusion

Interventions

PCI-32765

420 mg PO daily

Intervention Type: DRUG

ofatumumab

per package insert as an IV infusion

Intervention Type: DRUG

Other Intervention Names

ibrutinib; Arzerra

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ohio State University

OTHER

Sponsor Role: collaborator

Pharmacyclics LLC.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Samantha Jaglowski, MD

Role: PRINCIPAL_INVESTIGATOR

Ohio State University

Locations

The Ohio State University

Columbus, Ohio, United States

Countries

United States

References

Fraietta JA, Beckwith KA, Patel PR, Ruella M, Zheng Z, Barrett DM, Lacey SF, Melenhorst JJ, McGettigan SE, Cook DR, Zhang C, Xu J, Do P, Hulitt J, Kudchodkar SB, Cogdill AP, Gill S, Porter DL, Woyach JA, Long M, Johnson AJ, Maddocks K, Muthusamy N, Levine BL, June CH, Byrd JC, Maus MV. Ibrutinib enhances chimeric antigen receptor T-cell engraftment and efficacy in leukemia. Blood. 2016 Mar 3;127(9):1117-27. doi: 10.1182/blood-2015-11-679134. Epub 2016 Jan 26.

Reference Type: DERIVED

PMID: 26813675 (View on PubMed)

Maddocks KJ, Ruppert AS, Lozanski G, Heerema NA, Zhao W, Abruzzo L, Lozanski A, Davis M, Gordon A, Smith LL, Mantel R, Jones JA, Flynn JM, Jaglowski SM, Andritsos LA, Awan F, Blum KA, Grever MR, Johnson AJ, Byrd JC, Woyach JA. Etiology of Ibrutinib Therapy Discontinuation and Outcomes in Patients With Chronic Lymphocytic Leukemia. JAMA Oncol. 2015 Apr;1(1):80-7. doi: 10.1001/jamaoncol.2014.218.

Reference Type: DERIVED

PMID: 26182309 (View on PubMed)

Jaglowski SM, Jones JA, Nagar V, Flynn JM, Andritsos LA, Maddocks KJ, Woyach JA, Blum KA, Grever MR, Smucker K, Ruppert AS, Heerema NA, Lozanski G, Stefanos M, Munneke B, West JS, Neuenburg JK, James DF, Hall N, Johnson AJ, Byrd JC. Safety and activity of BTK inhibitor ibrutinib combined with ofatumumab in chronic lymphocytic leukemia: a phase 1b/2 study. Blood. 2015 Aug 13;126(7):842-50. doi: 10.1182/blood-2014-12-617522. Epub 2015 Jun 26.

Reference Type: DERIVED

PMID: 26116658 (View on PubMed)

Dubovsky JA, Beckwith KA, Natarajan G, Woyach JA, Jaglowski S, Zhong Y, Hessler JD, Liu TM, Chang BY, Larkin KM, Stefanovski MR, Chappell DL, Frissora FW, Smith LL, Smucker KA, Flynn JM, Jones JA, Andritsos LA, Maddocks K, Lehman AM, Furman R, Sharman J, Mishra A, Caligiuri MA, Satoskar AR, Buggy JJ, Muthusamy N, Johnson AJ, Byrd JC. Ibrutinib is an irreversible molecular inhibitor of ITK driving a Th1-selective pressure in T lymphocytes. Blood. 2013 Oct 10;122(15):2539-49. doi: 10.1182/blood-2013-06-507947. Epub 2013 Jul 25.

Reference Type: DERIVED

PMID: 23886836 (View on PubMed)

Related Links

http://Pharmacyclics.com

www.pharmacyclics.com

Other Identifiers

PCI-32765

Identifier Type: OTHER

Identifier Source: secondary_id

PCYC-1109-CA

Identifier Type: -

Identifier Source: org_study_id