Daratumumab for the Treatment of Patients With AL Amyloidosis

NCT02841033 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: H-3536054767414AMY2002
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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.

Conditions

AL Amyloidosis

Keywords

Daratumumab

Outcome Measures

Primary Outcomes (1)

• Assess the Number of Patients Who Respond to Treatment

  Number of participants with response and ability to tolerate study treatment in each of these categories: Complete Response (CR), Very Good Partial Response (VGPR), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD). All participants were able to tolerate study treatment. Per protocol, overall response designations are a combination of hematologic response. A CR is defined as negative serum and urine immunofixation electrophoresis with normal serum free light chain ratio; a VGPR is reduction in the dFLC\* to \<40 mg/L, a PR is dFLC reduction by \>50%; SD is not meeting criteria for CR, VGPR, PR, or PD; and PD is an increase in FLC of 50% to \>100 mg/L. \* "dFLC" is difference in involved and uninvolved serum Free Light-Chain levels.

  3 months

Secondary Outcomes (3)

• Time to Next Treatment

  Up to 3 years

• Assess Hematologic Response Based on Blood and Urine Testing Using Standard Criteria

  3 months

• Assess Organ Responses Based on Standard Criteria Included in Protocol

  3 months

Study Arms (1)

Daratumumab

EXPERIMENTAL

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.

Drug: daratumumab

Interventions

daratumumab 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.

Also known as: Darzalex

Daratumumab

Eligibility Criteria

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

You may qualify if:

• Histological diagnosis of primary systemic (AL) amyloidosis:
• At least one tissue demonstrating positive Congo Red staining with characteristic apple green birefringence AND
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Boston Medical Center: lead
• Janssen Pharmaceuticals: collaborator

Study Sites (1)

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Related Publications (1)

• 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.

  PMID: 31978210 DERIVED

Related Links

• creatinine clearance cockcroft-gault formula

MeSH Terms

Conditions

Immunoglobulin Light-chain Amyloidosis

Interventions

daratumumab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Amyloidosis; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Paraproteinemias

Results Point of Contact

• Title: Vaishali Sanchorawala, MD
• Organization: Boston Medical Center

vaishali.sanchorawala@bmc.org

617-638-8213

Study Officials

• Vaishali Sanchorawala, MD

  Boston Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: June 14, 2016
• First Posted: July 21, 2016
• Study Start: March 20, 2017
• Primary Completion: May 28, 2020
• Study Completion: July 17, 2020
• Last Updated: May 7, 2021
• Results First Posted: May 7, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)