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B-cell Chronic Lymphocytic LeukemiaPhase 1/2PCYC-1109-CANCT01217749

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

A Phase 1/2 study testing PCI-32765 and ofatumumab in people with B-cell Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by Pharmacyclics LLC. at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
PCI-32765 and ofatumumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
71 participants
Where
1 siteUnited States
Study dates
Dec 2010to May 2014
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 21Show fewer
  • 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
  • 10% 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
  • 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
  • No history of prior exposure to ofatumumab
  • Age ≥ 18 years
  • Body weight ≥ 40 kg

Who cannot join

  • 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
Show all 11Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • The Ohio State University

    Columbus, Ohio, 43210

Other trials in United States

About this study

Official title: An Open-label, Phase 1b/2, Safety and Efficacy Study of the Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI-32765, and Ofatumumab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and Prolymphocytic Leukemia

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

Being tested
PCI-32765, ofatumumab
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PCI-32765Drug

    Also called ibrutinib

    420 mg PO daily

  • ofatumumabDrug

    Also called Arzerra

    per package insert as an IV infusion

Study groups in NCT01217749
Study groupRoleWhat they receive
Group 1ExperimentalIn Group 1, PCI-32765 420 mg PO was administered daily for 1 cycle (28 days) before the start of ofatumumab IV dosing
Receives: Drug: PCI-32765; Drug: ofatumumab
Group 2ExperimentalIn Group 2, PCI-32765 420 mg PO daily was initiated concomitantly with ofatumumab IV (PCI-32765 initiated on Day 2 of Cycle 1)
Receives: Drug: PCI-32765; Drug: ofatumumab
Group 3ExperimentalIn Group 3, two cycles of ofatumumab IV were administered prior to the start of PCI-32765 420 mg PO daily
Receives: Drug: PCI-32765; Drug: ofatumumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. 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

    Measured: 56 days for Group 1 and 28 days for Group 2

Secondary outcomes (2)

  1. Number of Participants With Treatment Emergent Adverse Events (AEs)

    Number of participants who had experienced at least one treatment emergent AE

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

  2. Progression Free Survival (PFS) at 12 Months

    Progressive disease for CLL (Hallek) is characterized by ≥1 of the following:

    • Appearance of any new lesion, eg lymph nodes (> 1.5 cm), de novo hepatomegaly or splenomegaly, or other organ infiltrates
    • Increase of ≥50%
    • in longest diameter of any previous site
    • in hepatomegaly or splenomegaly
    • in blood lymphocytes with ≥5x109/L B cells with enlarging lymph node, liver, or spleen

    Progressive disease for B cell lymphoma (Cheson) is characterized by any new lesion or increase by ≥ 50% of previously involved sites from nadir:

    • Appearance of a new lesion(s) >1.5 cm in any axis, ≥ 50% increase in the SPD of >1 node, or ≥50% increase in longest diameter of a previously identified node >1 cm in short axis
    • Lesions PET+ if FDG-avid lymphoma or PET+ before therapy
    • 50% increase from nadir in the SPD of any liver or spleen lesions
    • New or recurrent BM involvement
    • Increase of ≥50% in blood lymphocytes with ≥5x109/L B cells within enlarging lymph node, liver, or spleen

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Oct 2010 (estimated)
  2. Study startDec 2010
  3. Primary completionJun 2013
  4. Study completionMay 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
71 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01217749
Sponsor's protocol ID
PCYC-1109-CA
Other IDs
PCI-32765
Acronym
PCYC-1109-CA
Status last verified
May 2015
First submitted
7 Oct 2010
Last updated
25 Jun 2015
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 26813675

  • 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.

    PubMed 26182309

  • 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.

    PubMed 26116658

  • 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.

    PubMed 23886836

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing PCI-32765 and ofatumumab in people with B-cell Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by Pharmacyclics LLC. at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Apr 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants Achieving Response (time frame: The median follow-up time on study for all treated participants is 12.5 (range 0.5-19.6) months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01217749, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2015.

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