Clinical trial NCT03474133: Brentuximab Vedotin as Alternative to the Autologous Stem Cell Transplantation in Relapsed and Refractory Classical Hodgkin's Lymphoma (BASALT)
Official title: Brentuximab Vedotin as Alternative to the Autologous Stem Cell Transplantation in Relapsed and Refractory Classical Hodgkin's Lymphoma (BASALT)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Hodgkin's Lymphoma
Keywords: Hodgkin's lymphoma
Hodgkin lymphoma
relapsed
refractory
brentuximab vedotin
autologous stem cell transplantation
Lead sponsor: Federal Research Institute of Pediatric Hematology, Oncology and Immunology
Sponsor class: OTHER
First posted: 2018-03-22
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study evaluate possibility of brentuximab vedotin, administered after first treatment failure (no response or relapse after I line therapy) of Hodgkin's lymphoma, to induce durable response or cure without autologous stem cell transplantation.

Detailed description: Brentuximab vedotin (BV) can induce durable response or cure in some patients with relapsed or refractory Hodgkin's lymphoma (RR HL) after autologous stem cell transplantation (ASCT) failure. It is expecting that BV alone administered earlier (after first treatment failure, without any additional treatment) can cure some RR HL patients and spare them from ASCT-associated risks and toxicity. Therefore in this study full course of BV which confirmed its curative potential in post-ASCT setting will be applicated to the potentially transplant-eligible RR HL patients immediately after first treatment failure, with a aim to assess curative potential of BV in this setting.

Eligibility criteria: Inclusion Criteria:

1. Male or female patients 18 years or older
2. Voluntary written informed consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
3. 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.
4. 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.
5. Patients must have a diagnosis of a morphologically confirmed cluster of differentiation antigen 30 {CD30)-positive classical Hodgkin's lymphoma with primary refractory course or relapse after adequate first-line chemotherapy (with morphologically confirmation of vital tumor)
6. PET-positive measurable disease (at least one lesion with Deauville score of \>3 and at \>1.5 cm on CT scan)
7. Performance status Eastern Cooperative Oncology Group (ECOG) \<3
8. Patients potentially eligible for subsequent ASCT according treating physician decision
9. Clinical laboratory values as specified below within 7 days before the first dose of study drug:

   * Absolute neutrophil count ≥ 1,500/µL unless there is known hematologic/solid tumor marrow involvement
   * Platelet count ≥ 75,000/ µL unless there is known marrow involvement of the disease
   * Total bilirubin must be \< 1.5 x the upper limit of the normal (ULN) unless the elevation is known to be due to Gilbert syndrome.
   * ALT or aspartate aminotransferase (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 HL tumor in liver.
   * Serum creatinine must be \< 2.0 mg/dL and/or creatinine clearance or calculated creatinine clearance \> 40 mL/minute.
   * Hemoglobin must be ≥ 8g/dL.

Exclusion Criteria:

1. More than one line of chemotherapy due to Classical Hodgkin's lymphoma (any salvage treatment)
2. Previous treatment with brentuximab vedotin
3. Female patient who are both lactating and breast-feeding or have a positive serum pregnancy test during the screening period
4. Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to the protocol.
5. Known cerebral or meningeal disease (HL or any other etiology), including signs or symptoms of progressive multifocal leukoencephalopathy (PML)
6. Symptomatic neurologic disease compromising normal activities of daily living or requiring medications
7. Any sensory or motor peripheral neuropathy greater than or equal to Grade 2
8. 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 (see appendix #1)
   * 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
   * Recent evidence (within 6 months before first dose of study drug) of a left-ventricular ejection fraction \<50%
9. Any active systemic viral, bacterial, or fungal infection requiring systemic antibiotics within 2 weeks prior to first study drug dose
10. Patients that have received other investigational agents within at least 5 half-lives of last dose of that prior treatment
11. Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of brentuximab vedotin.
12. Known human immunodeficiency virus (HIV) positive
13. Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection
14. Diagnosed or treated for another malignancy. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.

Primary outcomes:
measure: Continuous complete response (CCR) rate
timeFrame: 3 years
Secondary outcomes:
measure: Additional therapy-free survival (ATFS)
timeFrame: 3 years
measure: Overall survival
timeFrame: 3 year
measure: Incidence AE according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 [Safety]
timeFrame: 1 year
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: City clinical hospital №40
city: Saint Petersburg
country: Russian Federation
facility: R. Gorbacheva Research Institute of Pediatric Hematology and Transfusiology; Pavlov State Medical University of Saint-Petersburg
Study officials:
affiliation: Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology
name: Nikolay Zhukov, MD, Phd
role: PRINCIPAL_INVESTIGATOR
References: