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

Arbeitsgemeinschaft medikamentoese Tumortherapie

Status and phase

Terminated

Phase 2

Phase 1

Conditions

ALK+ Anaplastic Large Cell Lymphoma

Treatments

Drug: Imatinib

Drug: Brentuximab vedotin

Study type

Interventional

Funder types

Other

Identifiers

NCT02462538

AGMT_ALCL1

Details and patient eligibility

About

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.

Full description

Patients will be included in this trial if they have relapsed or refractory ALK+ ALCL after at least one line of conventional chemotherapy or if they are ineligible for conventional chemotherapy.

Imatinib will be given continuously starting from day 1 of the first cycle at an oral dose of 100mg daily. The dose will be increased to 200mg daily starting from day 1 of the second cycle if no DLT occurs during the first cycle. BV will be given 3 weekly starting on day 1 at a dose of 1.8 mg/kg body weight. In the absence of a dose limiting toxicity (DLT) i.e. haematological toxicity ≥ grade 2, non- haematological toxicity ≥ grade 3, after 3 weeks of therapy, and in the presence of a clinical response (CR or PR) after cycle 1, the BV dose will continue every 3 weeks for 48 weeks. Dose modifications and stopping rules will be introduced as described in chapter 6. In case of progression at any time during the study the patient will go off trial and receive salvage treatment.

Enrollment

3 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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.

Exclusion criteria

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
- Recent evidence (within 6 months before first dose of study drug) of a left-ventricular ejection fraction <50%
Any active systemic viral, bacterial, or fungal infection requiring systemic antibiotics within 2 weeks prior to first study drug dose
Diagnosed or treated for another malignancy within 3 years before the first dose or previously diagnosed with another malignancy and have evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.