BrEPEM-LH-22017 for Older Patients With Untreated Hodgkin Lymphoma (HL)

NCT03576378 | Active Not Recruiting Phase 1

• 1 other identifier: BrEPEM-LH-22017
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 15

Brief Summary

The purpose of the phase Ib of the study is to identify the maximum tolerated dose (MTD) of Brentuximab Vedotin (BV) in combination with EPEM and to assess the toxicity of the combination of BV with EPEM. In the phase II efficacy will be evaluated.Besides, progression-free survival (PFS), event-free survival (EFS), overall survival (OS), the duration of response, the overall response rate (ORR) based on best response will be evaluated

Conditions

Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (3)

• Phase Ib: maximum tolerated dose (MTD)

  To identify the maximum tolerated dose (MTD) of Brentuximab Vedotin (BV) in combination with EPEM

  Up to 28 days after start of each cycle

• Phase II: Complete response rate

  To assess the percentage of patients with complete response rate after BV-EPEM treatment.

  6 months after last patient start treatment

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  To evaluate the toxicity of the treatment by measure of number of treatment-related adverse events according to CTCAE v4.0

  Up to 28 days after start of each cycle

Secondary Outcomes (6)

• progression-free survival (PFS)

  At the end of eache cycle (every cycle is 28 days) and then every 3 months up to 3 years in the study

• Duration of response

  At the end of eache cycle (every cycle is 28 days) and then every 3 months up to 3 years in the study

• Overall response rate (ORR)

  At the end of eache cycle (every cycle is 28 days) and then every 3 months up to 3 years in the study

• Incidence of Treatment Adverse Events [Safety and Tolerability]

  At the end of eache cycle (every cycle is 28 days) and then every 3 months up to 3 years in the study

• event-free survival (EFS)

  At the end of eache cycle (every cycle is 28 days) and then every 3 months up to 3 years in the study

Study Arms (1)

Experimental: Brentuximab vedotin plus EPEM

EXPERIMENTAL

Brentuximab Vedotin dose will start at 1.2 mg/kg by intravenous (IV) infusion on Day1 and Day15 plus Cyclophosphamide 500mg/m2 IV on Day1 plus Procarbazine 100mg/m2 by mouth (OR) on Day1 through 5 plus Etoposide 60mg/m2 OR on Day15 through 19 plus Mitoxantrone 6mg/m2 IV on Day15 and Prednisone 30mg/m2 on Day1 through 5 of each 28-day treatment cycles for up to 6 total treatment cycles (approximately 24 weeks or 6 months)

Drug: BrentuximabVedotin (BV)

Interventions

BrentuximabVedotin (BV) DRUG

All patients will be treated with 6 cycles of BV-EPEM

Also known as: cyclophosphamide, procarbazine, prednisone, etoposide, mitoxantrone

Experimental: Brentuximab vedotin plus EPEM

Eligibility Criteria

• Age: 60 Years - 95 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females of 60 years of age or older.
• Previously untreated classical Hodgkin lymphoma (i.e., nodular sclerosis, mixed cellularity, lymphocyte depleted, lymphocyte-rich, and not otherwise specified \[NOS\]).
• Stage IIB, III, and IV disease by Ann Arbor classification.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.
• Patients must have bi-dimensional measurable disease documented in the lymphoma baseline tumor assessment form (PET-CT report) within 30 days prior to Screening (at least 1.5 cm)
• Patients must have a bone marrow biopsy within 60 days prior to screening.
• Patients must have a multi gated acquisition scan (MUGA) or echocardiogram within 60 days prior to study screening and the ejection fraction must be \>= 50%.
• Adequate hematologic function, defined as Absolute neutrophil count (ANC) ≥ 1,500/mm3 / 1x109/L and Platelet count ≥75,000/mm3 / 75x109/L unless there is known marrow involvement of the disease
• Serum Creatinine \< 2.0 mg/dl and/or creatinine clearance or calculated creatinine clearance \> 40 mL/minute.
• Total Bilirubin \< 1.5 x the upper limit of normal (ULN) unless elevation is known to be due to Gilbert syndrome.
• ALT or AST must be \< 3 x the upper limit of the normal range. AST and ALT may be elevated up to 5 times the ULN if their elevation can be reasonably ascribed to the presence of hematologic/solid tumour in liver.
• Hemoglobin must be ≥ 8g/dL
• Patients must not have received prior chemotherapy or radiation therapy for the treatment of Hodgkin lymphoma.
• Female patient is either post-menopausal for at least 2 years before the screening visit or surgically sterile or if of childbearing potential must agree to use two effective contraceptive methods, at the same time, from the time of signing the informed consent and for 6 months following the last dose of study drug, or agree to completely abstain from heterosexual intercourse.
• Male patients, even if surgically sterilized, (i.e., status post vasectomy) must agree to practice effective barrier contraception during the entire study period and through 6 months after the last dose of study drug, or agree to completely abstain from heterosexual intercourse.

You may not qualify if:

• Nodular lymphocyte predominant Hodgkin lymphoma
• Previous treatment with BV or any other prior anti-CD30-based antibody therapy
• Female patient who is both lactating and breast-feeding or has a positive pregnancy test during the screening period or a positive pregnancy test on Day 1 before the first dose of study drug
• History of another primary malignancy that has not been in remission for at least 3 years; (the following are exempt from the 3-year limit: early stage \[stage I or II\] breast cancer treated with surgery and radiation +/- hormones \[without adjuvant chemotherapy\], non-melanoma skin cancer, fully excised melanoma in situ \[stage 0\], curatively treated localized prostate cancer, and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on Papanicolaou test \[PAP smear\])
• Known cerebral/meningeal disease (HL or any other etiology), including signs or symptoms of progressive multifocal leukoencephalopathy (PML)
• Any active systemic viral, bacterial, or fungal infection requiring treatment with antimicrobial therapy within 1 week prior to first dose
• Known or suspected hepatitis B infection, or known or suspected active hepatitis C infection Known human immunodeficiency virus (HIV) positive
• Patients with a known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of brentuximab vedotin
• Patients with dementia or an altered mental state that would preclude the understanding and rendering of informed consent
• Symptomatic neurologic disease compromising normal activities of daily living or requiring medications
• Any sensory or motor peripheral neuropathy greater than or equal to 2
• Known history of any of the following cardiovascular conditions;
• Myocardial infarction within 2 years of enrollment
• New York Heart Association (NYHA) Class III or IV heart failure
• Evidence of uncontrolled cardiovascular conditions, including cardiac arrhythmias,congestive heart failure (CHF), angina, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities

Sponsors & Collaborators

• Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea: lead
• Takeda: collaborator

Study Sites (15)

Institut Català d'Oncologia, Hospital Germans Trias i Pujol

Badalona, Barcelona, Spain

Location

Institut Català d'Oncologia, Hospital Duran i Reynals

L'Hospitalet de Llobregat, Barcelona, Spain

Location

Hospital Costa del Sol

Marbella, Málaga, Spain

Location

Hospital Clinic i Provincial de Barcelona

Barcelona, Spain

Location

Hospital Vall d'Hebron

Barcelona, Spain

Location

Hospital de Basurto

Bilbao, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Hospital Universitario La Paz

Madrid, Spain

Location

Hospital Son Llatzer

Palma de Mallorca, Spain

Location

Hospital Universitario de Salamanca

Salamanca, Spain

Location

Hospital Universitario Donostia - Arantzazu

San Sebastián, Spain

Location

Hospital Universitario Marqués de Valdecilla

Santander, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, Spain

Location

Related Publications (18)

• Evens AM, Sweetenham JW, Horning SJ. Hodgkin lymphoma in older patients: an uncommon disease in need of study. Oncology (Williston Park). 2008 Nov 15;22(12):1369-79.

  PMID: 19086599 BACKGROUND

• Proctor SJ, Wilkinson J, Sieniawski M. Hodgkin lymphoma in the elderly: a clinical review of treatment and outcome, past, present and future. Crit Rev Oncol Hematol. 2009 Sep;71(3):222-32. doi: 10.1016/j.critrevonc.2008.12.007.

  PMID: 19179093 BACKGROUND

• Evens AM, Helenowski I, Ramsdale E, Nabhan C, Karmali R, Hanson B, Parsons B, Smith S, Larsen A, McKoy JM, Jovanovic B, Gregory S, Gordon LI, Smith SM. A retrospective multicenter analysis of elderly Hodgkin lymphoma: outcomes and prognostic factors in the modern era. Blood. 2012 Jan 19;119(3):692-5. doi: 10.1182/blood-2011-09-378414. Epub 2011 Nov 23.

  PMID: 22117038 BACKGROUND

• Engert A, Ballova V, Haverkamp H, Pfistner B, Josting A, Duhmke E, Muller-Hermelink K, Diehl V; German Hodgkin's Study Group. Hodgkin's lymphoma in elderly patients: a comprehensive retrospective analysis from the German Hodgkin's Study Group. J Clin Oncol. 2005 Aug 1;23(22):5052-60. doi: 10.1200/JCO.2005.11.080. Epub 2005 Jun 13.

  PMID: 15955904 BACKGROUND

• Ballova V, Ruffer JU, Haverkamp H, Pfistner B, Muller-Hermelink HK, Duhmke E, Worst P, Wilhelmy M, Naumann R, Hentrich M, Eich HT, Josting A, Loffler M, Diehl V, Engert A. A prospectively randomized trial carried out by the German Hodgkin Study Group (GHSG) for elderly patients with advanced Hodgkin's disease comparing BEACOPP baseline and COPP-ABVD (study HD9elderly). Ann Oncol. 2005 Jan;16(1):124-31. doi: 10.1093/annonc/mdi023.

  PMID: 15598949 BACKGROUND

• Halbsguth TV, Boll B, Borchmann P, Diehl V. The unique characteristics and management of patients over 60 years of age with classic Hodgkin lymphoma. Curr Hematol Malig Rep. 2011 Sep;6(3):164-71. doi: 10.1007/s11899-011-0089-7.

  PMID: 21553348 BACKGROUND

• Proctor SJ, Rueffer JU, Angus B, Breuer K, Flechtner H, Jarrett R, Levis A, Taylor P, Tirelli U. Hodgkin's disease in the elderly: current status and future directions. Ann Oncol. 2002;13 Suppl 1:133-7. doi: 10.1093/annonc/13.s1.133.

  PMID: 12078895 BACKGROUND

• Halbsguth TV, Nogova L, Mueller H, Sieniawski M, Eichenauer DA, Schober T, Nisters-Backes H, Borchmann P, Diehl V, Engert A, Josting A. Phase 2 study of BACOPP (bleomycin, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone) in older patients with Hodgkin lymphoma: a report from the German Hodgkin Study Group (GHSG). Blood. 2010 Sep 23;116(12):2026-32. doi: 10.1182/blood-2009-11-253211. Epub 2010 Jun 15.

  PMID: 20551376 BACKGROUND

• Boll B, Bredenfeld H, Gorgen H, Halbsguth T, Eich HT, Soekler M, Markova J, Keller U, Graeven U, Kremers S, Geissler M, Trenn G, Fuchs M, von Tresckow B, Eichenauer DA, Borchmann P, Engert A. Phase 2 study of PVAG (prednisone, vinblastine, doxorubicin, gemcitabine) in elderly patients with early unfavorable or advanced stage Hodgkin lymphoma. Blood. 2011 Dec 8;118(24):6292-8. doi: 10.1182/blood-2011-07-368167. Epub 2011 Sep 13.

  PMID: 21917759 BACKGROUND

• Levis A, Anselmo AP, Ambrosetti A, Adamo F, Bertini M, Cavalieri E, Gavarotti P, Genua A, Liberati M, Pavone V, Pietrasanta D, Ricetti MM, Scalabrini DR, Salvi F, Vitolo U, Angelucci E, Boccadoro M, Gallo E, Mandelli F; Intergruppo Italiano Linfomi (IIL). VEPEMB in elderly Hodgkin's lymphoma patients. Results from an Intergruppo Italiano Linfomi (IIL) study. Ann Oncol. 2004 Jan;15(1):123-8. doi: 10.1093/annonc/mdh012.

  PMID: 14679131 BACKGROUND

• Proctor SJ, Wilkinson J, Jones G, Watson GC, Lucraft HH, Mainou-Fowler T, Culligan D, Galloway MJ, Wood KM, McNally RJ, James PW, Goodlad JR. Evaluation of treatment outcome in 175 patients with Hodgkin lymphoma aged 60 years or over: the SHIELD study. Blood. 2012 Jun 21;119(25):6005-15. doi: 10.1182/blood-2011-12-396556. Epub 2012 May 10.

  PMID: 22577177 BACKGROUND

• Francisco JA, Cerveny CG, Meyer DL, Mixan BJ, Klussman K, Chace DF, Rejniak SX, Gordon KA, DeBlanc R, Toki BE, Law CL, Doronina SO, Siegall CB, Senter PD, Wahl AF. cAC10-vcMMAE, an anti-CD30-monomethyl auristatin E conjugate with potent and selective antitumor activity. Blood. 2003 Aug 15;102(4):1458-65. doi: 10.1182/blood-2003-01-0039. Epub 2003 Apr 24.

  PMID: 12714494 BACKGROUND

• Okeley NM, Miyamoto JB, Zhang X, Sanderson RJ, Benjamin DR, Sievers EL, Senter PD, Alley SC. Intracellular activation of SGN-35, a potent anti-CD30 antibody-drug conjugate. Clin Cancer Res. 2010 Feb 1;16(3):888-97. doi: 10.1158/1078-0432.CCR-09-2069. Epub 2010 Jan 19.

  PMID: 20086002 BACKGROUND

• Cerveny CG, Law CL, McCormick RS, Lenox JS, Hamblett KJ, Westendorf LE, Yamane AK, Petroziello JM, Francisco JA, Wahl AF. Signaling via the anti-CD30 mAb SGN-30 sensitizes Hodgkin's disease cells to conventional chemotherapeutics. Leukemia. 2005 Sep;19(9):1648-55. doi: 10.1038/sj.leu.2403884.

  PMID: 16049514 BACKGROUND

• Wahl AF, Klussman K, Thompson JD, Chen JH, Francisco LV, Risdon G, Chace DF, Siegall CB, Francisco JA. The anti-CD30 monoclonal antibody SGN-30 promotes growth arrest and DNA fragmentation in vitro and affects antitumor activity in models of Hodgkin's disease. Cancer Res. 2002 Jul 1;62(13):3736-42.

  PMID: 12097283 BACKGROUND

• Younes A, Bartlett NL, Leonard JP, Kennedy DA, Lynch CM, Sievers EL, Forero-Torres A. Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N Engl J Med. 2010 Nov 4;363(19):1812-21. doi: 10.1056/NEJMoa1002965.

  PMID: 21047225 BACKGROUND

• Younes A, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, Ramchandren R, Bartlett NL, Cheson BD, de Vos S, Forero-Torres A, Moskowitz CH, Connors JM, Engert A, Larsen EK, Kennedy DA, Sievers EL, Chen R. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin's lymphoma. J Clin Oncol. 2012 Jun 20;30(18):2183-9. doi: 10.1200/JCO.2011.38.0410. Epub 2012 Mar 26.

  PMID: 22454421 BACKGROUND

• Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials. 1989 Mar;10(1):1-10. doi: 10.1016/0197-2456(89)90015-9.

  PMID: 2702835 BACKGROUND

MeSH Terms

Conditions

Hodgkin Disease

Interventions

Cyclophosphamide; Procarbazine; Prednisone; Etoposide; Mitoxantrone

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Benzamides; Amides; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Glucosides; Glycosides; Carbohydrates; Anthraquinones; Anthrones; Anthracenes; Quinones

Study Officials

• FRANCESC BOSCH, MD Phd

  Hospital Vall d'Hebron

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: April 26, 2018
• First Posted: July 3, 2018
• Study Start: August 8, 2018
• Primary Completion: October 30, 2023
• Study Completion: October 30, 2024
• Last Updated: February 26, 2024

Record last verified: 2024-02

Locations

ES (15)