As described above, the survival rate of patients with relapsed or refractory Hodgkin's lymphoma has been increasing with the recent development of new drugs. However, due to limitations in the Korean health care system, there is a lack of research on the role of these drugs or combinations of these drugs in Korean patients with Hodgkin's lymphoma.
As already mentioned, DHAP is a salvage therapy that has been used for a long time for the treatment of lymphoma patients and is considered to have proven safety and clinical efficacy. In addition, this combination is deemed to be versatile in actual administration to patients as it is a combination of relatively low-cost drugs belonging to the group 1 anticancer drug combinations in the health insurance system. The combination of DHAP and BV has been proved for its safety and effectiveness in a study by a Western research group, but further research is needed to verify whether similar levels of safety and effectiveness can be secured in Korean patient with Hodgkin's lymphoma, who belong to a different race group.
Among the other main issues are whether patients with relapsed or refractory Hodgkin's lymphoma can achieve a PET-negative CR with the BV-DHAP combination at a higher probability; whether they can thus maintain a long-term survival after ASCT at a higher probability; and whether this can lead to the reduced need for follow-up treatment that requires more expensive drugs.
Therefore, the investigators propose a phase II trial in which induction therapy is conducted with pre-transplant the BV-DHAP combination for patients with relapsed or refractory Hodgkin's lymphoma.

Treatment

[Induction phase]
① Primary evaluation after 2 cycles of induction therapy (BV-DHAP)
- CR, PR, or SD : after PBSCC, treatment goes on to the next stage.
- PD : withdrawal
② Secondary evaluation after additional 1 cycle of induction therapy (BV-DHAP) (a total of 3 cycles)
    - CR or PR : ASCT 
    - SD or PD : withdrawal
③ Dosing schedule
Brentuximab vedotin , IV, 1.8mg/kg, D1			
Cisplatin , IV, 100mg/m2,  D1			
Cytarabine, IV, 2g/m2, D2 	            	
Dexamethasone ,IV or PO, 40mg, D1-D4         	

[Consolidation phase]
autologous stem cell transplant (ASCT) is performed in accordance with a protocol as per the site’s policy.		

Arm Label

Target Number of Participant

Arm Type

Arm Description

[Induction phase]
① Primary evaluation after 2 cycles of induction therapy (BV-DHAP)
- CR, PR, or SD : after PBSCC, treatment goes on to the next stage.
- PD : withdrawal
② Secondary evaluation after additional 1 cycle of induction therapy (BV-DHAP) (a total of 3 cycles)
    - CR or PR : ASCT 
    - SD or PD : withdrawal
③ Dosing schedule
Brentuximab vedotin , IV, 1.8mg/kg, D1			
Cisplatin , IV, 100mg/m2,  D1			
Cytarabine, IV, 2g/m2, D2 	            	
Dexamethasone ,IV or PO, 40mg, D1-D4	

[Consolidation phase]
autologous stem cell transplant (ASCT) is performed in accordance with a protocol as per the site’s policy.		

Gender

Age

Description

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

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

CR rate

after induction treatment

PFS, OS, ORR (after induction treatment & ASCT), rate of successful PBSCC, safety profile

after induction treatment & ASCT