Brentuximab Vedotin Plus DHAP in Relapsed or Refractory Hodgkin's Lymphoma

Brentuximab Vedotin Plus Cisplatin, Cytarabine, and Dexamethasone in Patients With Relapsed or Refractory Hodgkin's Lymphoma Who Are Eligible for Transplant

< STUDY DESIGN > This study is a multi-center phase II trial in patients with relapsed or refractory Hodgkin's lymphoma after first-line treatment.

< Treatment Schedule >

1. Induction phase

   • Patients who sign the informed consent form (ICF) receive BV-DHAP induction therapy within 21 days.
   • Tumor response is evaluated following 2 cycles of induction therapy. As a result of tumor response evaluation, PD (progressive disease) means a withdrawal from the study; and CR (complete response), PR (partial response), or SD (stable disease) requires peripheral blood stem cell collection (PBSCC) followed by additional one cycle of induction therapy.
   • Following a total of 3 cycles of induction therapy, tumor response is evaluated again. If the result turns out to be CR or PR, treatment goes on to autologous stem cell transplant (ASCT). SD or PD means a withdrawal from the study.
2. Consolidation phase - ASCT is performed in accordance with a protocol based on the relevant site's policy.

Study Overview

• Status: Recruiting
• Conditions: Relapsed/Refractory Classical Hodgkin Lymphoma
• Intervention / Treatment: Drug: Brentuximab vedotin

Detailed Description

< STUDY DESIGN > This study is a multi-center phase II trial in patients with relapsed or refractory Hodgkin's lymphoma after first-line treatment.

< Treatment Schedule >

1. Induction phase

   - Patients who sign the informed consent form (ICF) receive BV-DHAP induction therapy within 21 days.

   Study Drug Dosage will be as follows; Brentuximab vedotin: 1.8 mg/kg IV over 30 minutes D1 Cisplatin* 100 mg/m2 + NS 1000 mL CIV over 24 hours D1 Cytarabine* 2.0 g/m2 + 5% DW 250 mL IV over 3 hours twice a day D2 Dexamethasone 40 mg IV or PO D1-4

   *If baseline or on treatment creatinine clearance is less than 60 mL/min, 25% dose reduction should strongly be considered (cisplatin 75 mg/m2, cytarabine 1.5 g/m2)

   • Tumor response is evaluated following 2 cycles of induction therapy. As a result of tumor response evaluation, PD (progressive disease) means a withdrawal from the study; and CR (complete response), PR (partial response), or SD (stable disease) requires peripheral blood stem cell collection (PBSCC) followed by additional one cycle of induction therapy.
   • Following a total of 3 cycles of induction therapy, tumor response is evaluated again. If the result turns out to be CR or PR, treatment goes on to autologous stem cell transplant (ASCT). SD or PD means a withdrawal from the study.
   • Each cycle is implemented at an interval of 21 days (± 3 days).

2. Consolidation phase

   • ASCT is performed in accordance with a protocol based on the relevant site's policy.
   • Conditioning regimen will be determined by the attending physician. For example, BEAM, BuCyEtopo, BeEAM (Bendamustine+EAM), etc.
   • Other conservative managements will be carried out according to the policy of participating site

< Follow-Up Schedule >

• Patients will be recruited up to 3 years from the start date of this study.
• Primary analysis and reporting will be carried out at the completion of ASCT of the last patient.
• PFS and OS will be followed up for up to 2 years from the completion of ASCT of the last patient. Final analysis will be reported at this point.
• After completion of ASCT, a patient will be followed up at an interval of 3 months for 2 years

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hyeon-Seok Eom, MD, PhD; Phone Number: +82-31-920-2402; Email: hseom@ncc.re.kr

Study Locations

• Korea, Republic of
  • Gyeonggi-do
    • Goyang, Gyeonggi-do, Korea, Republic of, 10408
      • Recruiting
      • Hyeon-Seok Eom
      • Contact: Hyeon-Seok Eom; Phone Number: 0319201505; Email: hseom@ncc.re.kr
      • Contact: Jun-Ho Yi; Email: xuno@daum.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histologically confirmed diagnosis of classical Hodgkin's lymphoma. CD30 has to be positive

2. Refractory to the first-line treatment or relapse after the first-line treatment (radiologically confirmed)

   • Deauville score 5 as a result of the restaging PET-CT after 2 to 3 cycles of ABVD treatment
   • Deauville score 4 to 5 even after the completion of ABVD treatment or radiotherapy and are not candidates for ISRT (involved site radiation therapy)
   • Radiologically confirmed relapsed after achieving CR

3. At least one measurable lesion(s)

   • nodal lesion longest transverse diameter (LDi) ≥ 1.5 cm
   • extranodal lesion LDi ≥ 1.0 cm)
4. Age 19 to 70 years
5. ECOG PS 0 - 2
6. Appropriate organ functions to tolerate the protocol treatment and ASCT Absolute Neutrophil Count (ANC) ≥ 1.5 x 10^9/L Platelets ≥ 75 x 10^9/L Hemoglobin ≥ 8.0 g/dL Serum Creatinine ≤ 1.5 x upper limit normal (ULN) Serum Bilirubin ≤ 1.5 x ULN AST and ALT ≤ 3 x ULN Corrected diffusing capacity for carbon monoxide (DLCO) ≥50 percent
7. Female patient is either post-menopausal for at least 1 year before the screening visit or surgically sterile or if of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 6 months after the last dose of study drug, or agrees to completely abstain from heterosexual intercourse.
8. Male patients, even if surgically sterilized, (i.e., status post vasectomy) agree to practice effective barrier contraception during the entire study period and through 6 months after the last dose of study drug, or agrees to completely abstain from heterosexual intercourse.
9. Written informed consent

Exclusion Criteria:

1. Non-Hodgkin's lymphoma or nodular lymphocyte predominant Hodgkin's lymphoma
2. 2 or more prior lines of treatment (Palliative radiotherapy or high-dose steroid therapy for symptom control are allowed)
3. Known cerebral or meningeal disease (HL or any other etiology), including signs or symptoms of PML
4. Confirmed CNS involvement and/or symptomatic neurologic disease compromising normal activities of daily living or requiring medications
5. Patients who cannot tolerate high-dose therapy followed by ASCT described in the inclusion criteria 6.
6. Patients with severe or uncontrolled medical conditions, abnormal laboratory findings, or psychiatric disorders. For example, i. severely impaired pulmonary function as defined as spirometry and DLCO (diffusing capacity of the lung for carbon monoxide) that is 50% or less of the normal predicted value and/or O2 saturation that is 90% or less at rest on room air ii. any active (acute or chronic) or uncontrolled infection/disorders that impair the ability to evaluate the patient or for the patient to complete the study iii. nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by this study drug, such as severe hypertension that is not controlled with medical management and thyroid abnormalities when thyroid function cannot be maintained in the normal range by medication iv. creatinine clearance < 30 mL/min
7. Known history of any of the following cardiovascular conditions i. Myocardial infarction within 2 years of enrollment ii. New York Heart Association (NYHA) Class III or IV heart failure iii. Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure (CHF), angina, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities iv. Recent evidence (within 6 months before first dose of study drug) of a left-ventricular ejection fraction <50%
8. Synchronous or metachronous malignant tumor other than HL within 5 years (except for adequately treated basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) of the skin, carcinoma in situ of the uterine cervix, adequately resected differentiated thyroid cancer, intraepithelial carcinoma of the neck or breast, or prostate cancer that can be monitored for progress status without any treatment).
9. Hypersensitivity to the investigational products.
10. Peripheral neuropathy ≥ Grade 2
11. Pregnant or nursing women
12. Human immunodeficiency virus (HIV)-positive
13. Active hepatitis B or hepatitis C infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Brentuximab vedotin and DHAP; A clinical study of safety and efficacy of treatment with Brentuximab vedotin and DHAP in patients with relapsed/refractory Hodgkin lymphoma	Drug: Brentuximab vedotin; 3 cycles of Brentuximab vedotin and DHAP; Other Names: Adcetris

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response rate	Tumor response is evaluated following 3 cycles (each cycle is 21 days) of BV + DHAP induction therapy	up to 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	PFS after BV + DHAP induction treatment & ASCT	up to 24 months
Overall survival	PFS after BV + DHAP induction treatment & ASCT	up to 24 months
Overall response rate	Tumor response is evaluated following 3 cycles (each cycle is 21 days) of BV+ DHAP induction therapy	up to 3 months
Safety profiles	Frequency of grade 3 or higher treatment-related adverse events by CTCAE 5.0	up to 3 months

Collaborators and Investigators

• Sponsor: National Cancer Center, Korea
• Investigators: Principal Investigator: Hyeon-Seok Eom, MD, PhD, National Cancer Center

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2022
• Primary Completion (Anticipated): February 28, 2024
• Study Completion (Anticipated): March 31, 2026

Study Registration Dates

• First Submitted: January 2, 2022
• First Submitted That Met QC Criteria: February 12, 2022
• First Posted (Actual): February 17, 2022

Study Record Updates

• Last Update Posted (Actual): February 17, 2022
• Last Update Submitted That Met QC Criteria: February 12, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Hodgkin Disease; Antineoplastic Agents; Antineoplastic Agents, Immunological; Brentuximab Vedotin
• Other Study ID Numbers: NCC2020-0293

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No