Ofatumumab + Chlorambucil vs Chlorambucil Monotherapy in Previously Untreated Patients With Chronic Lymphocytic Leukemia

NCT ID: NCT00748189

Last Updated: 2019-06-25

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

447 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-12-22

Study Completion Date

2018-05-17

Brief Summary

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The purpose of this study was to evaluate the safety and efficacy of ofatumumab added to chlorambucil in patients with untreated Chronic Lymphocytic Leukemia.

Detailed Description

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Chlorambucil, is currently approved for treatment of frontline chronic lymphocytic leukemia, especially, but not limited to the ailing and elderly patient population. Several other more aggressive treatment options are available (e.g. fludarabine), however they are not suitable for all CLL patients, especially the ailing and elderly, due to greater toxicity. Ofatumumab is effective with low toxicity. The addition of ofatumumab to chlorambucil offers potentially a more effective therapy, with limited toxicity. The objective of this study was to evaluate progression-free survival (PFS), overall response and overall survival in subjects with previously untreated CLL with ofatumumab added to chlorambucil versus chlorambucil.

Conditions

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Leukaemia, Lymphocytic, Chronic

Study Design

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Allocation Method

RANDOMIZED

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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ofatumumab + chlorambucil

ofatumumab dose: cycle 1 300mg day 1 and 1000mg day 8, subsequent cycles: 1000mg at day 1 every 28 days; chlorambucil dose: 10mg/m2 PO at days 1-7 every 28 days; duration: minimum of 3 cycles until best response or maximum of 12 treatment cycles

Group Type EXPERIMENTAL

chlorambucil, tablets

Intervention Type DRUG

2mg tablets, chlorambucil dose: 10mg/m2 PO at days 1-7 every 28 days; duration: minimum of 3 cycles until best response or maximum of 12 cycles

ofatumumab (GSK1841157) infusion

Intervention Type DRUG

iv infusion; dose: cycle 1 300mg day 1 and 1000mg day 8, subsequent cycles: 1000mg at day 1 every 28 days;

chlorambucil

chlorambucil dose: 10mg/m2 PO at days 1-7 every 28 days; duration: minimum of 3 cycles until best response or maximum of 12 cycles

Group Type ACTIVE_COMPARATOR

chlorambucil, tablets

Intervention Type DRUG

2mg tablets, chlorambucil dose: 10mg/m2 PO at days 1-7 every 28 days; duration: minimum of 3 cycles until best response or maximum of 12 cycles

Interventions

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chlorambucil, tablets

2mg tablets, chlorambucil dose: 10mg/m2 PO at days 1-7 every 28 days; duration: minimum of 3 cycles until best response or maximum of 12 cycles

Intervention Type DRUG

ofatumumab (GSK1841157) infusion

iv infusion; dose: cycle 1 300mg day 1 and 1000mg day 8, subsequent cycles: 1000mg at day 1 every 28 days;

Intervention Type DRUG

Other Intervention Names

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chlorambucil tablets

Eligibility Criteria

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Inclusion Criteria

* confirmed CLL diagnosis and active CLL requiring treatment
* considered inappropriate for fludarabine-based therapy
* not been treated for CLL before
* fully active at a minimum or fully capable of selfcare and up and about more than 50% of waking hours
* age 18yrs or older
* signed written informed consent

Exclusion Criteria

* prior CLL therapy
* abnormal/inadequate blood values, liver, and kidney function
* certain heart problems, active or chronic infections, serious significant diseases, active autoimmune hemolytic anemia (AIHA) requiring treatment, other current cancer or within last 5 years
* CLL transformation
* CLL central nervous system involvement
* current participation in other clinical study
* inability to comply with the protocol activities
* lactating or pregnant women or female patients of child-bearing potential (or male patients with such partners) not willing to use adequate contraception
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Novartis Investigative Site

Sedona, Arizona, United States

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Tucson, Arizona, United States

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Murrieta, California, United States

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Aurora, Colorado, United States

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Denver, Colorado, United States

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Boca Raton, Florida, United States

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New Port Richey, Florida, United States

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Ocala, Florida, United States

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Ocoee, Florida, United States

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Marietta, Georgia, United States

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Chicago, Illinois, United States

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Indianapolis, Indiana, United States

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Lee's Summit, Missouri, United States

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Raleigh, North Carolina, United States

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Abilene, Texas, United States

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Arlington, Texas, United States

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Austin, Texas, United States

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Odessa, Texas, United States

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San Antonio, Texas, United States

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Tyler, Texas, United States

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Waco, Texas, United States

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Webster, Texas, United States

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Seattle, Washington, United States

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Vancouver, Washington, United States

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Yakima, Washington, United States

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Bruges, , Belgium

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Brussels, , Belgium

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Ghent, , Belgium

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Haine-Saint-Paul, , Belgium

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Leuven, , Belgium

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Porto Alegre, Rio de Janeiro, Brazil

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Sherbrooke, Quebec, Canada

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Brno, , Czechia

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Hradec Králové, , Czechia

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Frankfurt am Main, Hesse, Germany

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Hanover, Lower Saxony, Germany

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Lehrte, Lower Saxony, Germany

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Cologne, North Rhine-Westphalia, Germany

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Udine, , Italy

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Luleå, , Sweden

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Uppsala, , Sweden

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Swindon, , United Kingdom

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Uxbridge, , United Kingdom

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Countries

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United States Belgium Brazil Canada Czechia France Germany Greece India Ireland Italy Netherlands Poland Russia Spain Sweden United Kingdom

References

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Tausch E, Beck P, Schlenk RF, Jebaraj BJ, Dolnik A, Yosifov DY, Hillmen P, Offner F, Janssens A, Babu GK, Grosicki S, Mayer J, Panagiotidis P, McKeown A, Gupta IV, Skorupa A, Pallaud C, Bullinger L, Mertens D, Dohner H, Stilgenbauer S. Prognostic and predictive role of gene mutations in chronic lymphocytic leukemia: results from the pivotal phase III study COMPLEMENT1. Haematologica. 2020 Oct 1;105(10):2440-2447. doi: 10.3324/haematol.2019.229161.

Reference Type DERIVED
PMID: 33054084 (View on PubMed)

Hillmen P, Robak T, Janssens A, Babu KG, Kloczko J, Grosicki S, Doubek M, Panagiotidis P, Kimby E, Schuh A, Pettitt AR, Boyd T, Montillo M, Gupta IV, Wright O, Dixon I, Carey JL, Chang CN, Lisby S, McKeown A, Offner F; COMPLEMENT 1 Study Investigators. Chlorambucil plus ofatumumab versus chlorambucil alone in previously untreated patients with chronic lymphocytic leukaemia (COMPLEMENT 1): a randomised, multicentre, open-label phase 3 trial. Lancet. 2015 May 9;385(9980):1873-83. doi: 10.1016/S0140-6736(15)60027-7. Epub 2015 Apr 14.

Reference Type DERIVED
PMID: 25882396 (View on PubMed)

Jewell RC, Laubscher K, Lewis E, Fang L, Gafoor Z, Carey J, McKeown A, West S, Wright O, Sedoti D, Dixon I, Hottenstein CS, Chan G. Assessment of the effect of ofatumumab on cardiac repolarization. J Clin Pharmacol. 2015 Jan;55(1):114-21. doi: 10.1002/jcph.376. Epub 2014 Aug 21.

Reference Type DERIVED
PMID: 25103870 (View on PubMed)

Other Identifiers

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OMB110911

Identifier Type: OTHER

Identifier Source: secondary_id

OMB110911

Identifier Type: -

Identifier Source: org_study_id

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