Frailty Score-guided Dosing of Lenalidomide, Dexamethasone and Daratumumab Induction Therapy

NCT04223661 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: CTO-IUSCC-0719
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine if using a subject's baseline frailty score to guide the dosing of lenalidomide in a combination with dexamethasone and daratumumab (DRd lite).

Conditions

Multiple Myeloma

Keywords

multiple myeloma

Outcome Measures

Primary Outcomes (5)

• Response Rate

  Based on the International Myeloma Working group criteria

  3 months

• Response Rate

  Based on the International Myeloma Working group criteria

  6 months

• Response Rate

  Based on the International Myeloma Working group criteria

  12 months

• Response Rate

  Based on the International Myeloma Working group criteria

  Best response achieved (up to but no longer than 2 years)

• Side Effects

  Evaluated based on CTCAE version 5.0

  up to 730 days

Secondary Outcomes (5)

• Time on therapy

  up to 730 days

• Progression free survival

  up to 730 days

• Time to the next line of therapy

  up to 730 days

• European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire

  Monthly (months 1-6), then every 3 months until treatment end (up to but no longer than 2 years)

• Quality of Life- Myeloma

  Monthly (months 1-6), then every 3 months until treatment end (up to but no longer than 2 years)

Study Arms (2)

Frailty score 1

EXPERIMENTAL

Starting dose of lenalidomide in subjects who are intermediately fit (frailty score of 1) will be 10 mg day 1-21 of 28 day cycle and escalate to 15 mg All subjects will receive 20mg Dexamathasone weekly (split dosing is allowed) and 16mg Daratumumab (cycle 1-2 on days 1,8,15 and 22. Cycles 3-6 on days 1 and 15. Cycle 7 and beyond on day 1) during the course of the trial.

Drug: Lenalidomide Pill; Drug: Dexamethasone; Drug: Daratumumab

Frailty Score 2 or above

EXPERIMENTAL

Starting dose of lenalidomide in frail subjects (frailty score of 2 or higher) will be 5 mg day 1-21 of 28 day cycle, and escalate to 10 mg. All subjects will receive 20mg Dexamathasone weekly (split dosing is allowed) and 16mg Daratumumab (cycle 1-2 on days 1,8,15 and 22. Cycles 3-6 on days 1 and 15. Cycle 7 and beyond on day 1) during the course of the trial.

Drug: Lenalidomide Pill; Drug: Dexamethasone; Drug: Daratumumab

Interventions

Lenalidomide Pill DRUG

Lenalidomide will be administered PO on Days 1 through 21 of each 28 day cycle at the dose according to the frailty score and creatinine clearance.

Frailty Score 2 or above; Frailty score 1

Dexamethasone DRUG

Dexamethasone will be administered at 20 mg per week. During weeks when the subject receives an infusion of daratumumab, dexamethasone will be administered on infusion days at a dose of 20 mg IV before the infusion.

Frailty Score 2 or above; Frailty score 1

Daratumumab DRUG

Daratumumab (1800 mg) will be administered by SC injection by manual push over approximately 3 - 5 minutes in the abdominal subcutaneous tissues in the left/right locations, alternating between individual doses. The volume of the SC solution will be 15 mL for the 1800 mg dose

Frailty Score 2 or above; Frailty score 1

Eligibility Criteria

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

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Newly diagnosed, symptomatic MM who have frailty score of 1 or higher; patients age ≥ 75 or younger patients with comorbidities (\<75):
• Frailty score takes into account age, as well as the geriatric assessments incorporating 3 tools: the Katz Activity of Daily Living (ADL), the Lawton Instrumental Activity of Daily Living (IADL), and the Charlson Comorbidity Index (CCI)-see detailed tables in Appendix A.
• Score calculation tool: www.myelomafrailtyscorecalculator.net
• ECOG (Eastern Cooperative Oncology Group) Performance Status of 0-2 within 14 days prior to registration.
• Measurable disease according to the International Myeloma Working Group criteria:
• Serum M-protein ≥1 g/dL
• Urine M-protein ≥200 mg/24 h, or
• Serum FLC (free light-chain) assay: involved FLC level ≥10 mg/dL provided serum FLC ratio is abnormal
• Clonal bone marrow plasma cells ≥ 10%
• No prior systemic therapy for myeloma is allowed. Surgery such as vertebroplasty or intramedullary rod placements, and local palliative radiation are allowed as long as subjects have no residual AEs (adverse events) from prior therapies at the time of screening
• Life expectancy of \>3 months as determined by the treating physician.
• Demonstrate adequate organ function as defined in the table below; all screening labs to be obtained within 14 days prior to registration.
• System Laboratory Value Hematological\* Absolute Neutrophil Count (ANC) ≥ 1.0 K/mm3 Platelet ≥ 50 K/mm3 Hemoglobin (Hgb) ≥ 8 g/dL Renal Calculated creatinine clearance ≥ 30 mL/min using 24 hour urine creatinine clearance Hepatic Bilirubin ≤ 2 × upper limit of normal (ULN) Aspartate aminotransferase (AST) ≤ 2 × ULN Alanine aminotransferase (ALT) ≤ 2 × ULN Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT) ≤ 2 × ULN
• Females of childbearing potential must have a negative serum pregnancy test within 14 days prior to registration. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months

You may not qualify if:

• Prior or concurrent exposure to any of the following:
• To daratumumab or other anti-CD-38 therapies
• Maximum of 40 mg dexamethasone (or equivalent) daily for a maximum of 4 days consecutively up to 21 days of 1st dose
• Exposure to investigational drug (including investigational vaccines) or invasive investigational medical device for any indication within 4 weeks or 5 pharmacokinetic half-lives, whichever is longer, before enrollment \[Cycle 1, Day 1 / Randomization\]
• Focal radiation therapy within 14 days prior to enrollmentrandomization with the exception of palliative radiotherapy for symptomatic management but not on measurable extramedullary plasmacytoma. Radiotherapy within 14 days prior to enrollmentrandomization on measurable extramedullary plasmacytoma is not permitted even in the setting of palliation for symptomatic management.
• Known allergies, hypersensitivity, or intolerance to any of the study drugs, hyaluronidase, mannitol, sorbitol or, corticosteroids, monoclonal antibodies, human proteins, or their excipients.
• Active infection requiring systemic therapy
• Poorly controlled reactive airway diseases including COPD (chronic obstructive pulmonary disease) or asthma. In subjects with underlying disease of COPD or asthma, spirometric analysis is recommended. Subjects with FEV1 (forced expiratory volume at one second) \< 50% is excluded.
• Other medical conditions interfering with the administration of and compliance to treatments such as Cardiac disease (such as myocardial infarction within past 6 months, uncontrolled cardiac arrhythmia, congestive cardiac failure), major surgeries within past 2 weeks, plasmapheresis within past 28 days
• Plasma cell leukemia or amyloidosis
• Pregnant or breastfeeding
• Known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the subject has been disease-free for at least five years.
• Active central nervous system (CNS) involvement by MM
• Contraindication to receive antiplatelet or anticoagulant prophylaxis
• Subject is:

Sponsors & Collaborators

• Attaya Suvannasankha: lead
• Janssen Scientific Affairs, LLC: collaborator
• Indiana Institute for Medical Research: collaborator

Study Sites (1)

VA Roudebush Medical Center

Indianapolis, Indiana, 46202, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Lenalidomide; Dexamethasone; daratumumab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Attaya Suvannasankha, MD

  Indiana University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Model Details: Starting dose of lenalidomide in subjects who are intermediately fit (frailty score of 1) will be 10 mg day 1-21 of 28 day cycle and escalate to 15 mg, and in frail subjects (frailty score of 2 or higher) will be 5 mg, and escalate to 10 mg. All subjects will receive 20mg Dexamathasone and 1800mg Daratumumab during the course of the trial.

Study Record Dates

• First Submitted: December 3, 2019
• First Posted: January 10, 2020
• Study Start: December 6, 2021
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2023
• Last Updated: December 8, 2022

Record last verified: 2022-12

Locations

US (1)