Daratumumab for the Treatment of Patients With AL Amyloidosis

NCT ID: NCT02841033

Last Updated: 2021-05-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-20
• Study Completion Date: 2020-07-17

Brief Summary

Participants with AL Amyloidosis will receive the drug daratumumab by IV infusion once weekly for two months, then every 2 weeks for four months, then once each month. Study treatment may continue until disease progression, unacceptable toxicity, or decision to withdraw from the trial. Disease evaluations will be performed every three months until disease progression.

Detailed Description

This Phase I/II study is intended to evaluate the safety and tolerability of infusion of daratumumab in AL amyloidosis, specifically with respect to infusion reactions. In addition, the investigators would like to assess organ response with respect to cardiac biomarkers and proteinuria, as well as hematologic response and time to next treatment. Participants with AL Amyloidosis will receive the drug daratumumab by IV infusion once weekly for two months, then every 2 weeks for four months, then once each month. Study treatment may continue until disease progression, unacceptable toxicity, or decision to withdraw from the trial. Disease evaluations will be performed every three months until disease progression.

Conditions

AL Amyloidosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Daratumumab

Daratumumab, 16mg/kg body weight in 1000 mL for the first dose, followed by 500mL for subsequent doses, once weekly for two months, then every 2 weeks for four months, then once each month.

Group Type: EXPERIMENTAL

daratumumab

Intervention Type: DRUG

Daratumumab by IV infusion once weekly for two months, then every 2 weeks for four months, then once each month until progression or inability to tolerate.

Interventions

daratumumab

Daratumumab by IV infusion once weekly for two months, then every 2 weeks for four months, then once each month until progression or inability to tolerate.

Intervention Type: DRUG

Other Intervention Names

Darzalex

Eligibility Criteria

Inclusion Criteria

• Histological diagnosis of primary systemic (AL) amyloidosis:

1. At least one tissue demonstrating positive Congo Red staining with characteristic apple green birefringence AND

2. Evidence of a clonal plasma cell dyscrasia:

i. Monoclonal protein in the serum and/or urine by immunofixation electrophoresis AND/OR ii. Abnormal serum free light chain assay AND/OR iii. Clonal plasma cell population in the bone marrow demonstrated by immunohistochemistry, flow cytometry or in situ hybridization AND

c. Evidence of organ involvement other than carpal tunnel syndrome. Confirmation of tissue diagnosis at all sites of organ dysfunction is encouraged, but not required.

• Must have relapsed after or been refractory to at least one prior treatment regimen of proven efficacy in the treatment of AL amyloidosis
• Must be > 18 years of age.
• Must have a performance status of 0-2 by Eastern Cooperative Oncology Group (ECOG) criteria
• Must have adequate hepatic function as evidenced by serum bilirubin values < 2.0 mg/dL; alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) < 3x upper limit of normal (ULN).
• Must have an absolute neutrophil count ≥1000/mm3, hemoglobin ≥7.5 g/dL, and platelet count ≥50×109/L

Exclusion Criteria

• • Renal Insufficiency (CrCL <20mL/min), calculated by Cockcroft-Gault Equation Creatinine Clearance = Sex * ((140 - Age) / (SerumCreat)) * (Weight / 72) Equation parameters such as sex have two or more discrete values that may be used in the calculation. The numbers in the parentheses, e.g. (1), represent the values that will be used. The default unit of measure for weight is kilograms. Please verify that the correct unit of measure has been selected.

• Mayo clinic cardiac biomarker stage IIIb
• Evidence of significant cardiovascular conditions as specified below:
• B-type Natriuretic Peptide; N-terminal pro b-type Natriuretic Peptide (NT-ProBNP) > 8500 ng/L (Mayo Stage IIIb patients are excluded)
• New York Heart Association (NYHA) classification IIIB or IV heart failure
• Unstable Angina, Arrhythmia, prolonged corrected QT (QTc) interval, symptomatic orthostatic hypotension, or supine systolic blood pressure < 90 mm Hg.
• left ventricular ejection fraction (LVEF) <40%

• Overt multiple myeloma (>30% bone marrow plasmacytosis, extensive (>2) lytic lesions, or hypercalcemia).
• Plan for autologous stem cell transplant in the six months prior to study drug (stem cell collection is permitted during the first six months of study treatment)
• Any form of secondary or familial (ATTR) amyloidosis
• The presence or history of another malignancy is not allowed except for the following:

• adequately treated basal cell or squamous cell skin cancer,
• in situ cervical cancer,
• adequately treated Stage I or II cancer from which the patient is currently in complete remission, any other cancer from which the patient has been disease-free for 5 years.
• Known to be Human Immunodeficiency Virus (HIV) positivity.
• Pregnant or nursing women. Women and men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
• Known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume at one second (FEV1) <50% of predicted normal. Note that forced expiratory volume at one second FEV1 testing is required for patients suspected of having COPD.
• Known moderate or severe persistent asthma within the past 2 years or currently has uncontrolled asthma of any classification

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Boston Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vaishali Sanchorawala, MD

Role: PRINCIPAL_INVESTIGATOR

Boston Medical Center

Locations

Boston Medical Center

Boston, Massachusetts, United States

Countries

United States

References

Sanchorawala V, Sarosiek S, Schulman A, Mistark M, Migre ME, Cruz R, Sloan JM, Brauneis D, Shelton AC. Safety, tolerability, and response rates of daratumumab in relapsed AL amyloidosis: results of a phase 2 study. Blood. 2020 Apr 30;135(18):1541-1547. doi: 10.1182/blood.2019004436.

Reference Type: DERIVED

PMID: 31978210 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://reference.medscape.com/calculator/creatinine-clearance-cockcroft-gault

creatinine clearance cockcroft-gault formula

Other Identifiers

54767414AMY2002

Identifier Type: OTHER

Identifier Source: secondary_id

H-35360

Identifier Type: -

Identifier Source: org_study_id