Brentuximab Vedotin and Imatinib in Patients With Relapsed or Refractory ALK+ ALCL

NCT02462538 | Terminated Phase 1

• 1 other identifier: AGMT_ALCL1
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label pilot study of combining BV in a licensed indication with imatinib in patients with ALCL. It is intended as a "window of opportunity" trial in which the study drugs will be given as an initial substitute for conventional chemotherapy with the intention to achieve a remission enabling the patients to proceed to autologous or allogeneic stem cell transplantation, if eligible.

Conditions

ALK+ Anaplastic Large Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Safety of brentuximab vedotin and imatinib regime as measured by type, frequency and severity of adverse events (AEs) and their relationship to study treatment

  up to 6 years

Secondary Outcomes (4)

• Efficacy of brentuximab vedotin and imatinib regime as measured by proportion of patients responding to treatment

  up to 6 years

• Ability to receive further Treatment as measured by number of patients being able to receive transplantation

  up to 6 years

• Progression-free survival as measured by proportion of patients displaying progressive disease

  up to 6 years

• Overall survival as measured by documentation of deaths

  up to 6 years

Study Arms (1)

Brentuximab vedotin and Imatinib

EXPERIMENTAL

Brentuximab vedotin (every 3 weeks i.v., 1.8 mg/kg) and imatinib (200mg daily orally, escalated from 100mg daily) for up to 48 weeks

Drug: Brentuximab vedotin; Drug: Imatinib

Interventions

Brentuximab vedotin DRUG

Brentuximab vedotin is given in a 21 day cycle intravenously starting at 1.8 mg/kg on day 1 of the first cycle and will be administered by IV infusion given over approximately 30 minutes on day 1 of each 21-day cycle.

Also known as: Adcetris

Brentuximab vedotin and Imatinib

Imatinib DRUG

Imatinib will be given orally at a dose of 100mg daily starting from day 1 of the first cycle. The dose will be increased to 200mg daily starting from day 1 of the second cycle if no DLT occurs during the first cycle and will be continued at 200mg for 48 weeks.

Also known as: Glivec

Brentuximab vedotin and Imatinib

Eligibility Criteria

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

You may qualify if:

• Patients ≥ 18 years of age
• ALK+ ALCL
• Histologically confirmed relapse after having achieved a PR or CR with conventional therapy
• Refractoriness to conventional chemotherapy (SD or PD after conventional chemotherapy)
• Not able to receive conventional chemotherapy (e.g. due to comorbidities)
• Adequate organ function, defined as the following:
• 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 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 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.
• Written, voluntarily signed informed consent
• Female patient is either post-menopausal for at least 1 year before the screening visit or surgically sterile or if of childbearing potential, must practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent until 6 months after the last doses of BV and until last doses of imatinib, whatever occurs later, or agrees to completely abstain from heterosexual intercourse.
• 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 BV, or agrees to completely abstain from heterosexual intercourse.

You may not qualify if:

• Patient has received any other investigational treatment within 28 days before study entry
• Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of brentuximab vedotin or imatinib
• ECOG performance status ≥ 3
• Acute or chronic infections
• Female patients who are pregnant or breast-feeding
• Known diagnosis of HIV
• Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection
• Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to the protocol.
• Known cerebral or meningeal disease (HL or any other etiology), including signs or symptoms of PML
• Symptomatic neurologic disease compromising normal activities of daily living or requiring medications
• Any sensory or motor peripheral neuropathy greater than or equal to Grade 2
• Known history of any of the following cardiovascular conditions
• Myocardial infarction within 2 years of study entry
• New York Heart Association (NYHA) Class III or IV heart failure
• 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

Sponsors & Collaborators

• Arbeitsgemeinschaft medikamentoese Tumortherapie: lead

Study Sites (1)

Universitätsklinik f. Innere Medizin I, AKH Wien, Klinische Abteilung für Hämatologie und Hämostaseologie

Vienna, 1090, Austria

Location

MeSH Terms

Interventions

Brentuximab Vedotin; Imatinib Mesylate

Intervention Hierarchy (Ancestors)

Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Ulrich Jäger, MD

  Universitätsklinik für Innere Medizin I: Klinische Abteilung für Hämatologie und Hämostaseologie

  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: May 18, 2015
• First Posted: June 4, 2015
• Study Start: November 3, 2015
• Primary Completion: November 3, 2021
• Study Completion: November 3, 2021
• Last Updated: March 3, 2022

Record last verified: 2022-02

Locations

AU (1)