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BCD With or Without Doxycycline in Mayo Stage II-III Light Chain Amyloidosis Patients

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ClinicalTrials.gov Identifier: NCT03401372
Recruitment Status : Recruiting
First Posted : January 17, 2018
Last Update Posted : July 18, 2019
Sponsor:
Collaborators:
Peking University First Hospital
Chinese PLA General Hospital
Beijing Chao Yang Hospital
West China Hospital Affiliated with Sichuan University
Tongji Hospital Affiliated with Tongji Medical College of HUST
Union Hospital Affiliated with Tongji Medical College of HUST
Shanghai Changzheng Hospital
Nanfang Hospital of Southern Medical University
Information provided by (Responsible Party):
Jian Li, Peking Union Medical College Hospital

Brief Summary:
Survival of intermediate and high-risk primary light chain amyloidosis (pAL) remains poor due to high mortality within 3-6 months of diagnosis. Rapidly effective regimens such as bortezomib, cyclophosphamide and dexamethasone (BCD) still failed to overcome the poor prognosis in very advanced pAL amyloidosis patients. Recently, doxycycline was demonstrated to induce disruption of fibril formation and reduce the number of intact fibrils in transgenic mouse model of pAL amyloidosis. Furthermore, case-control study suggested that adjuvant oral doxycycline could improve response and survival in cardiac pAL amyloidosis, which necessities further confirmation through a randomized trial. Therefore, we designed a multi-center randomized open-label controlled study to investigate the efficacy and safety of co-administration of oral doxycycline with BCD regimen in treatment-naïve patients with Mayo stage II-III pAL amyloidosis. The primary outcome progression-free survival, and secondary endpoints including overall survival, hematologic response, organ response and toxicity of doxycycline will be evaluated.

Condition or disease Intervention/treatment Phase
Amyloidosis; Systemic Drug: Doxycycline Drug: Bortezomib Drug: Cyclophosphamide Drug: Dexamethasone Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 140 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Comparison of Bortezomib-Cyclophosphamide-Dexamethasone Chemotherapy With or Without Doxycycline in Newly Diagnosed Mayo Stage II-III Light Chain Amyloidosis Patients: A Multi-center Randomized Controlled Trial
Actual Study Start Date : April 21, 2018
Estimated Primary Completion Date : April 20, 2020
Estimated Study Completion Date : April 20, 2020


Arm Intervention/treatment
Experimental: Doxycycline/BCD chemotherapy
Doxycycline combined with bortezomib-cyclophosphamide-dexamethasone chemotherapy
Drug: Doxycycline
Oral doxycycline 100mg twice daily

Drug: Bortezomib
1.3mg/m2 of intravenous bortezomib on days 1, 8, 15 and 22 of a 35-day cycle

Drug: Cyclophosphamide
300mg/m2 cyclophosphamide on days 1, 8 and 15 of a 35-day cycle

Drug: Dexamethasone
40mg of dexamethasone on days 1, 8, 15 and 22 of a 35-day cycle

Active Comparator: BCD chemotherapy
Bortezomib-cyclophosphamide-dexamethasone chemotherapy
Drug: Bortezomib
1.3mg/m2 of intravenous bortezomib on days 1, 8, 15 and 22 of a 35-day cycle

Drug: Cyclophosphamide
300mg/m2 cyclophosphamide on days 1, 8 and 15 of a 35-day cycle

Drug: Dexamethasone
40mg of dexamethasone on days 1, 8, 15 and 22 of a 35-day cycle




Primary Outcome Measures :
  1. Progression-free survival [ Time Frame: 2 years ]
    The patients are assessed after each cycle of chemotherapy following treatment initiation until progression, relapse, death or study closure at 24-month follow-up.


Secondary Outcome Measures :
  1. Overall survival [ Time Frame: 2 years ]
    The patients are assessed after each cycle of chemotherapy following treatment initiation until progression, relapse, death or study closure at 24-month follow-up. If the primary endpoint has reached, patients will also be followed up every 3 months thereafter until death or study closure.

  2. Hematologic response [ Time Frame: 2 years ]
    The patients are assessed after each cycle of chemotherapy following treatment initiation until progression, relapse, death or study closure at 24-month follow-up. If the primary endpoint has reached, patients will also be followed up every 3 months thereafter until death or study closure.

  3. Organ response [ Time Frame: 2 years ]
    The patients are assessed after each cycle of chemotherapy following treatment initiation until progression, relapse, death or study closure at 24-month follow-up. If the primary endpoint has reached, patients will also be followed up every 3 months thereafter until death or study closure.

  4. Adverse events [ Time Frame: up to 2 years ]
    Adverse events are collected until 30 days after last dose of doxycycline.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • ≥18 years old adults.
  • Biopsy proved treatment-naïve pAL amyloidosis.
  • Mayo 2004 stage II-III.
  • dFLC > 40mg/L.
  • Patient must provide informed consent.

Exclusion Criteria:

  • Co-morbidity of uncontrolled infection.
  • Co-morbidity of grade 2 or 3 atrioventricular block.
  • Co-morbidity of sustained or recurrent nonsustained ventricular tachycardia.
  • Co-morbidity of other active malignancy.
  • Co-diagnosis of multiple myeloma or waldenstrom macroglobulinemia.
  • Grade 2 or higher neuropathy according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0.
  • Allergic history of doxycycline.
  • Neutrophil <1×10E9/L,hemoglobin < 7g/dL,or platelet < 75×10E9/L.
  • Severely compromised hepatic or renal function: ALT or AST > 2.5 × ULN, total bilirubin > 1.5mg/dL,or eGFR < 60mL/min.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03401372


Contacts
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Contact: Jian Li, MD +86-18610852525 lijian@pumch.cn
Contact: Kaini Shen, MD +86-13693339884 shenkaini3@sina.com

Locations
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China
Peking Union Medical College Hospital Recruiting
Beijing, China, 100730
Contact: Jian Li, MD         
Sponsors and Collaborators
Jian Li
Peking University First Hospital
Chinese PLA General Hospital
Beijing Chao Yang Hospital
West China Hospital Affiliated with Sichuan University
Tongji Hospital Affiliated with Tongji Medical College of HUST
Union Hospital Affiliated with Tongji Medical College of HUST
Shanghai Changzheng Hospital
Nanfang Hospital of Southern Medical University
Investigators
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Study Director: Jian Li, MD Peking Union Medical College Hospital

Publications of Results:

Other Publications:
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Responsible Party: Jian Li, Professor, Peking Union Medical College Hospital
ClinicalTrials.gov Identifier: NCT03401372     History of Changes
Other Study ID Numbers: PUMCH-AL2017
First Posted: January 17, 2018    Key Record Dates
Last Update Posted: July 18, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Jian Li, Peking Union Medical College Hospital:
Primary light chain amyloidosis
Doxycycline
Bortezomib
Prognosis
Progression-free survival
Overall survival
Organ response
Additional relevant MeSH terms:
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Immunosuppressive Agents
Amyloidosis
Proteostasis Deficiencies
Metabolic Diseases
Doxycycline
Dexamethasone
Dexamethasone acetate
Cyclophosphamide
Bortezomib
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Anti-Bacterial Agents