A Prospective Cohort of Obinutuzumab and Chlorambucil (GC) Chemotherapy for the Treatment of Elderly Patients With Chronic Lymphocytic Leukemia Including Next- Generation Sequencing (NGS)-Based Assessment

Chronic Lymphocytic Leukemia Clinical Trial

Official title:

A Prospective Cohort of Obinutuzumab and Chlorambucil (GC) Chemotherapy for the Treatment of Elderly Patients With Chronic Lymphocytic Leukemia Including Next- Generation Sequencing (NGS)-Based Assessment

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04059081
• Other study ID #: ML40990
• Status: Recruiting
• Phase: Phase 2
• Start date: July 9, 2019
• Est. completion date: July 8, 2022

Study information

• Verified date: August 2019
• Source: Chonnam National University Hospital
• Contact: Deok-Hwan Yang, M.D., Ph.D.
• Email: drydh1685[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 31
• Est. completion date: July 8, 2022
• Est. primary completion date: July 8, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 70 Years and older

Eligibility

Inclusion Criteria:

• Eligible subjects will be considered for inclusion in this study if they meet all of the following criteria:

1. Newly diagnosed chronic lymphocytic leukemia

2. Age= 70 years

3. Satisfy the one of indications for starting treatment guideline

1. Evidence of progressive marrow failure (anemia, thrombocytopenia)

2. AIHA, thrombocytopenia refractory to steroids

3. Massive (>6cm, LCM) or symptomatic splenomegaly

4. Massive nodes (>10 cm) or symptomatic

5. Progressive lymphocytosis

6. 50% increase over 2 months or LDT < 6 months

7. 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

Exclusion Criteria:

1. Unmet NGS samples by bone marrow biopsy or peripheral bloods at diagnosis

2. Hairy cell leukemia or prolymphocytic leukemia

3. Uncontrolled infection

4. Therapy history with combined chemotherapy or biologic therapy prior to registration

5. History of thromboembolic episodes = 3 months prior to registration

6. Active hepatitis B or C with uncontrolled disease

7. Active other malignancy requiring treatment that would interfere with the assessments of response of the lymphoma to protocol treatment

8. Any severe and/or uncontrolled medical conditions or other conditions that could adversely impact their ability to participate in the study

9. Concurrent participation in another therapeutic clinical trial.

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Drug:
• Obinutuzumab
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.

Locations

Country	Name	City	State
Korea, Republic of	Chonnam National University Hwasun Hospital	Hwasun	Jeollanam-do

Sponsors (2)

Lead Sponsor	Collaborator
Deok-Hwan Yang	Roche Pharma AG

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (9)

Eichhorst BF, Busch R, Stilgenbauer S, Stauch M, Bergmann MA, Ritgen M, Kranzhöfer N, Rohrberg R, Söling U, Burkhard O, Westermann A, Goede V, Schweighofer CD, Fischer K, Fink AM, Wendtner CM, Brittinger G, Döhner 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. — View Citation

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. Review. — View Citation

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, Döhner 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. — View Citation

Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner 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. — View Citation

Herling CD, Klaumünzer M, Rocha CK, Altmüller J, Thiele H, Bahlo J, Kluth S, Crispatzu G, Herling M, Schiller J, Engelke A, Tausch E, Döhner H, Fischer K, Goede V, Nürnberg 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. — View Citation

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. — View Citation

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, Lhéritier V, Beldjord K, Béné 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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate	iwCLL criteria	3 years
Secondary	Complete remission rate	No evidence of disease at the time of tumor assessment by NGS method	3 years
Secondary	Progression free survival	the time from first dose to documented disease progression	3 years
Secondary	Overall survival	the time from first dose to death from any cause	3 years