NCT04059081

Brief Summary

This study is prospective, open-label, single arm observational study to assess efficacy of obinutuzumab plus chlorambucil (GC) chemotherapy in treatment naïve CLL, and prognostic impact of genetic alterations for CLL using NGS.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
31

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Jul 2019

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 9, 2019

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

August 15, 2019

Completed
1 day until next milestone

First Posted

Study publicly available on registry

August 16, 2019

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 8, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 8, 2022

Completed
Last Updated

August 16, 2019

Status Verified

August 1, 2019

Enrollment Period

3 years

First QC Date

August 15, 2019

Last Update Submit

August 15, 2019

Conditions

Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (1)

  • Overall response rate

    iwCLL criteria

    3 years

Secondary Outcomes (3)

  • Complete remission rate

    3 years

  • Progression free survival

    3 years

  • Overall survival

    3 years

Study Arms (1)

GC chemotherapy

EXPERIMENTAL

Before administration of GC chemotherapy, all patients must undergo pretreatment bone marrow biopsy. The pretreatment BM biopsy must include at least 1 long core biopsy samples and 10 cc of aspirate. Obinutuzumab 1000mg fixed dose will be administered intravenously (Day 1,8,15 for cycle 1 and D1 for subsequent cycles). Chlorambucil 0.5mg/kg will be administered orally (D1,15 for all cycles). 28 days are considered as one cycle, and cycles will be repeated every 4-weeks for a total of 6 cycles.

Drug: Obinutuzumab

Interventions

ObinutuzumabDRUG

Obinutuzumab is provided as single-use vials for intravenous administration only. Obinutuzumab 1000mg fixed dose will be administered Chlorambucil would be provided as oral tablet with dose of 0.5mg/kg Day 1 to day 28 is considered one cycle, and cycles will be repeated every 4-weeks, until 6 cycles.

GC chemotherapy

Eligibility Criteria

Age70 Years+
Sexall
Healthy VolunteersNo
Age GroupsOlder Adult (65+)

You may qualify if:

  • Newly diagnosed chronic lymphocytic leukemia
  • Age≥ 70 years
  • Satisfy the one of indications for starting treatment guideline
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  • Evidence of progressive marrow failure (anemia, thrombocytopenia)
  • AIHA, thrombocytopenia refractory to steroids
  • Massive (\>6cm, LCM) or symptomatic splenomegaly
  • Massive nodes (\>10 cm) or symptomatic
  • Progressive lymphocytosis
  • % increase over 2 months or LDT \< 6 months
  • Constitutional Symptoms : weight loss \> 10% in 6 months, significant fatigue, fever \>38 over 2 weeks, night sweat \> 1month 4. ECOG performance status 0-2 5. Total bilirubin ≤ 1.5 x ULN (upper limit of normal) 6. Aspartate aminotransferase (AST) ≤ 5 x ULN, (ALT) ≤ 5 x ULN 7. Creatinine ≤ 3.0 x ULN 8. Provide informed consent Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information

You may not qualify if:

  • Unmet NGS samples by bone marrow biopsy or peripheral bloods at diagnosis
  • Hairy cell leukemia or prolymphocytic leukemia
  • Uncontrolled infection
  • Therapy history with combined chemotherapy or biologic therapy prior to registration
  • History of thromboembolic episodes ≤ 3 months prior to registration
  • Active hepatitis B or C with uncontrolled disease
  • Active other malignancy requiring treatment that would interfere with the assessments of response of the lymphoma to protocol treatment
  • Any severe and/or uncontrolled medical conditions or other conditions that could adversely impact their ability to participate in the study
  • Concurrent participation in another therapeutic clinical trial.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Chonnam National University Hwasun Hospital

Hwasun, Jeollanam-do, 519-809, South Korea

RECRUITING

Related Publications (9)

  • Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Dohner H, Hillmen P, Keating M, Montserrat E, Chiorazzi N, Stilgenbauer S, Rai KR, Byrd JC, Eichhorst B, O'Brien S, Robak T, Seymour JF, Kipps TJ. iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood. 2018 Jun 21;131(25):2745-2760. doi: 10.1182/blood-2017-09-806398. Epub 2018 Mar 14.

    PMID: 29540348BACKGROUND

  • Goede V, Fischer K, Busch R, Engelke A, Eichhorst B, Wendtner CM, Chagorova T, de la Serna J, Dilhuydy MS, Illmer T, Opat S, Owen CJ, Samoylova O, Kreuzer KA, Stilgenbauer S, Dohner H, Langerak AW, Ritgen M, Kneba M, Asikanius E, Humphrey K, Wenger M, Hallek M. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med. 2014 Mar 20;370(12):1101-10. doi: 10.1056/NEJMoa1313984. Epub 2014 Jan 8.

    PMID: 24401022BACKGROUND

  • Fabbri G, Dalla-Favera R. The molecular pathogenesis of chronic lymphocytic leukaemia. Nat Rev Cancer. 2016 Mar;16(3):145-62. doi: 10.1038/nrc.2016.8.

    PMID: 26911189BACKGROUND

  • Herling CD, Klaumunzer M, Rocha CK, Altmuller J, Thiele H, Bahlo J, Kluth S, Crispatzu G, Herling M, Schiller J, Engelke A, Tausch E, Dohner H, Fischer K, Goede V, Nurnberg P, Reinhardt HC, Stilgenbauer S, Hallek M, Kreuzer KA. Complex karyotypes and KRAS and POT1 mutations impact outcome in CLL after chlorambucil-based chemotherapy or chemoimmunotherapy. Blood. 2016 Jul 21;128(3):395-404. doi: 10.1182/blood-2016-01-691550. Epub 2016 May 25.

    PMID: 27226433BACKGROUND

  • Woyach JA, Ruppert AS, Heerema NA, Zhao W, Booth AM, Ding W, Bartlett NL, Brander DM, Barr PM, Rogers KA, Parikh SA, Coutre S, Hurria A, Brown JR, Lozanski G, Blachly JS, Ozer HG, Major-Elechi B, Fruth B, Nattam S, Larson RA, Erba H, Litzow M, Owen C, Kuzma C, Abramson JS, Little RF, Smith SE, Stone RM, Mandrekar SJ, Byrd JC. Ibrutinib Regimens versus Chemoimmunotherapy in Older Patients with Untreated CLL. N Engl J Med. 2018 Dec 27;379(26):2517-2528. doi: 10.1056/NEJMoa1812836. Epub 2018 Dec 1.

    PMID: 30501481BACKGROUND

  • Kim JA, Hwang B, Park SN, Huh S, Im K, Choi S, Chung HY, Huh J, Seo EJ, Lee JH, Bang D, Lee DS. Genomic Profile of Chronic Lymphocytic Leukemia in Korea Identified by Targeted Sequencing. PLoS One. 2016 Dec 13;11(12):e0167641. doi: 10.1371/journal.pone.0167641. eCollection 2016.

    PMID: 27959900BACKGROUND

  • Maury S, Chevret S, Thomas X, Heim D, Leguay T, Huguet F, Chevallier P, Hunault M, Boissel N, Escoffre-Barbe M, Hess U, Vey N, Pignon JM, Braun T, Marolleau JP, Cahn JY, Chalandon Y, Lheritier V, Beldjord K, Bene MC, Ifrah N, Dombret H; for GRAALL. Rituximab in B-Lineage Adult Acute Lymphoblastic Leukemia. N Engl J Med. 2016 Sep 15;375(11):1044-53. doi: 10.1056/NEJMoa1605085.

    PMID: 27626518BACKGROUND

  • Thomas DA, O'Brien S, Faderl S, Garcia-Manero G, Ferrajoli A, Wierda W, Ravandi F, Verstovsek S, Jorgensen JL, Bueso-Ramos C, Andreeff M, Pierce S, Garris R, Keating MJ, Cortes J, Kantarjian HM. Chemoimmunotherapy with a modified hyper-CVAD and rituximab regimen improves outcome in de novo Philadelphia chromosome-negative precursor B-lineage acute lymphoblastic leukemia. J Clin Oncol. 2010 Aug 20;28(24):3880-9. doi: 10.1200/JCO.2009.26.9456. Epub 2010 Jul 26.

    PMID: 20660823BACKGROUND

  • Eichhorst BF, Busch R, Stilgenbauer S, Stauch M, Bergmann MA, Ritgen M, Kranzhofer N, Rohrberg R, Soling U, Burkhard O, Westermann A, Goede V, Schweighofer CD, Fischer K, Fink AM, Wendtner CM, Brittinger G, Dohner H, Emmerich B, Hallek M; German CLL Study Group (GCLLSG). First-line therapy with fludarabine compared with chlorambucil does not result in a major benefit for elderly patients with advanced chronic lymphocytic leukemia. Blood. 2009 Oct 15;114(16):3382-91. doi: 10.1182/blood-2009-02-206185. Epub 2009 Jul 15.

    PMID: 19605849BACKGROUND

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

obinutuzumab

Condition Hierarchy (Ancestors)

Leukemia, B-CellLeukemia, LymphoidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Central Study Contacts

Deok-Hwan Yang, M.D., Ph.D.

CONTACT

drydh1685@hotmail.com

Young-il Koh, M.D., Ph.D.

CONTACT

snuhgo01@gmail.net

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
M.D., Ph.D.

Study Record Dates

First Submitted

August 15, 2019

First Posted

August 16, 2019

Study Start

July 9, 2019

Primary Completion

July 8, 2022

Study Completion

July 8, 2022

Last Updated

August 16, 2019

Record last verified: 2019-08

Locations

KR(1)