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

NCT01217749 | Completed Phase 1 Results DMC

• 2 other identifiers: PCYC-1109-CAPCI-32765
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants Achieving Response

  The primary endpoint for the study was overall response rate (ORR), defined as the proportion of participants who achieved a best overall response of complete response (CR), CR with incomplete blood count recovery (Cri), or partial response (PR), according to the guidelines from the International Workshop on Chronic Lymphocytic Leukemia (IWCLL1) published in 2008 for CLL participants and International Working Group for non-Hodgkin's lymphoma (IWG NHL) 2007 criteria for SLL participants, with the modification that treatment-related lymphocytosis will not be considered progressive disease, as evaluated by the investigators. Assessment of disease is based on radiological exams, physical exam, hematological evaluations and, when appropriate, bone marrow results.

  The median follow-up time on study for all treated participants is 12.5 (range 0.5-19.6) months

• Safety During Dose-Limiting Toxicity (DLT) Observation Period

  Number of dose-limiting toxicities observed in the first 6 participants enrolled in treatment Groups 1 and 2

  56 days for Group 1 and 28 days for Group 2

Secondary Outcomes (2)

• Number of Participants With Treatment Emergent Adverse Events (AEs)

  From first dose of study treatment to within 30 days of last dose or until study closure

• Progression Free Survival (PFS) at 12 Months

  From first dose of study treatment until disease progression, death, or until 12 months

Study Arms (3)

Group 1

EXPERIMENTAL

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

Drug: PCI-32765; Drug: ofatumumab

Group 2

EXPERIMENTAL

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

Drug: PCI-32765; Drug: ofatumumab

Group 3

EXPERIMENTAL

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

Drug: PCI-32765; Drug: ofatumumab

Interventions

PCI-32765 DRUG

420 mg PO daily

Also known as: ibrutinib

Group 1; Group 2; Group 3

ofatumumab DRUG

per package insert as an IV infusion

Also known as: Arzerra

Group 1; Group 2; Group 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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
• % expression of CD20 on CLL/SLL cells
• ECOG performance status ≤ 2
• Life expectancy ≥ 12 weeks
• 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

You may not qualify if:

• 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
• Significant cardiovascular disease
• 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
• 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
• 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
• Active central nervous system (CNS) involvement by lymphoma
• Major surgery within 4 weeks before first dose of study drug
• Lactating or pregnant
• Known moderate to severe chronic obstructive pulmonary disease (COPD)
• 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
• History of Grade ≥ 2 toxicity continuing from prior anticancer therapy including radiation

Sponsors & Collaborators

• Pharmacyclics LLC.: lead
• Ohio State University: collaborator

Study Sites (1)

The Ohio State University

Columbus, Ohio, 43210, United States

Location

Related Publications (4)

• 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.

  PMID: 26813675 DERIVED

• 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.

  PMID: 26182309 DERIVED

• 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.

  PMID: 26116658 DERIVED

• 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.

  PMID: 23886836 DERIVED

Related Links

• www.pharmacyclics.com

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

ibrutinib; ofatumumab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Jutta K. Neuenburg
• Organization: Pharmacyclics, Inc.

medinfo@pcyc.com

877-877-3536

Study Officials

• Samantha Jaglowski, MD

  Ohio State University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2010
• First Posted: October 8, 2010
• Study Start: December 1, 2010
• Primary Completion: June 1, 2013
• Study Completion: May 1, 2014
• Last Updated: June 25, 2015
• Results First Posted: April 16, 2015

Record last verified: 2015-05

Locations

US (1)