A Study of an Accelerated Infusion Rate of Daratumumab in Patients With Relapsed and Refractory Multiple Myeloma

NCT03697629 | Completed Phase 2 DMC

• 1 other identifier: CMRG 009
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 6

Brief Summary

Primary objective: To determine the incidence of infusion related reactions (IRR's) in the first 6 months of daratumumab administration.

Conditions

Multiple Myeloma in Relapse

Keywords

Multiple Myeloma; Relapse; Refractory; Daratumumab; Accelerated Infusion

Outcome Measures

Primary Outcomes (1)

• Incidence of infusion related reactions (IRRs)

  For an accelerated infusion schedule compared to the approved schedule

  First 6 months of daratumumab administration

Secondary Outcomes (2)

• Overall response rate (ORR)

  6 months of daratumumab administration

• Safety (adverse events) of study treatment

  6 months of daratumumab administration

Study Arms (1)

Daratumumab

EXPERIMENTAL

Increased infusion rate daratumumab monotherapy

Drug: Daratumumab

Interventions

Daratumumab DRUG

Patients will receive daratumumab, in the following schedule: Daratumumab 8mg/kg in 500 mL over 4 hours Cycle 1 Day 1, Daratumumab 16mg/kg in 500 mL over 90 minutes (20% of dose given in first 30 minutes and remaining 80% of dose given over 60 minutes) Cycle 1 Days 8, 15 and 22; Cycle 2 Days 1, 8, 15, and 22, and on Days 1 and 15 for Cycles 3-6.

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:

• Males or females, age 18 years or older.
• ECOG performance status score of 0, 1 or 2.
• Life expectancy of at least 3 months
• Measurable disease according to the IMWG criteria defined below (These baseline laboratory studies for determining eligibility must be obtained during the screening period within 28 days prior to start of study drug):
• Serum monoclonal paraprotein (M-protein) ≥ 10 g/L (if IgG) or ≥5g/L (if IgA, D, E or M).
• Urine M-protein ≥ 200 mg/24 h.
• Serum free light chains (FLC) assay: Involved FLC level ≥ 100 mg/L and an abnormal serum free light chain ratio (\< 0.26 or \> 1.65)
• Received at least 3 prior lines of therapy including a proteasome inhibitor (≥2 cycles or 2 months of treatment) and an IMiD (≥2 cycles or 2 months of treatment) in any order or in combination during the course of treatment or subjects whose disease is double refractory to a PI and an IMiD. For subjects who have received more than 1 type of PI, their disease must be refractory to the most recent one. Similarly, for those who have received more than 1 type of IMID, their disease must be refractory to the most recent one.
• \*\*A single line of therapy may consist of 1 or more agents, and may include induction, hematopoietic stem cell transplantation, and maintenance therapy (refer to Appendix 2). Radiotherapy, bisphosphonate, or a single short course of steroids (i.e. less than or equal to the equivalent of dexamethasone 40 mg/day for 4 days) would not be considered prior lines of therapy.
• Have achieved at least a minimal response (MR) or better to at least one previous line of therapy as per IMWG response criteria.
• The following laboratory results must be met within 10 days of first study drug administration:
• ANC ≥ 1.0 x 109/L
• Hemoglobin ≥ 80 g/L
• Platelets ≥ 70 x 109/L (or ≥50 x 109/L if ≥ 50% plasmacytosis in bone marrow)
• Calculated or measured CrCl ≥ 30 mL/min

You may not qualify if:

• Prior exposure to daratumumab (or other anti-CD38 monoclonal antibody).
• History of prior allogeneic stem cell transplantation and showing evidence of active graft-versus-host disease or graft-versus-host disease that requires immunosuppressive therapy.
• Chemotherapy or other anti-myeloma therapy within 14 days prior to the first dose of study drug.
• Treatment-related toxicity that has not recovered ≤Grade 1 unless deemed to be irreversible (an example of an irreversible toxicity would include steroid induced cataracts).
• Subjects who have received steroids within 2 weeks prior to starting study treatment or who have not recovered from side effects of such therapy. Concomitant therapy medications that include corticosteroids are allowed if subject receive ≤ 10 mg of prednisone per day, or equivalent, as indicated for other medical conditions, or up to 100 mg of hydrocortisone as pre-medication for administration of certain medications or blood products prior to enrolment in this study.
• Subjects who have received any investigational agents within 28 days or 5 half-lives (whichever is shorter, however the minimum allowed timeframe is 14 days) of the first dose (Cycle 1 Day 1).
• Prior history of malignancies, other than MM, unless the subject has been free of the disease for 3 years or longer. Exceptions include the following:
• Basal or squamous cell carcinoma of the skin
• Carcinoma in situ of the cervix or breast
• Adenocarcinoma of the prostate (TNM stage of T1a or T1b)
• Other concurrent severe and/or uncontrolled medical conditions (i.e. uncontrolled diabetes, active or uncontrolled infection, acute diffuse pulmonary disease, pericardial disease, uncontrolled thyroid dysfunction) including abnormal laboratory values, that could cause unacceptable safety risks or compromise compliance with the protocol.
• Known chronic obstructive pulmonary disease (COPD), defined as a FEV1 \< 50% predicted value.
• Known moderate or severe persistent asthma within the last 2 years, or currently has uncontrolled asthma of any classification.
• History of or current uncontrolled cardiovascular disease including:
• Unstable angina, myocardial infarction, or known congestive heart failure Class III/IV (Appendix 4) within the preceding 12 months

Sponsors & Collaborators

• Canadian Myeloma Research Group: lead

Study Sites (6)

Kingston Health Sciences Centre

Kingston, Ontario, K7L 2V7, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Hôpital Maisonneuve-Rosemont

Montreal, Quebec, H1T 2M4, Canada

Location

McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada

Location

Hôpital de l'Enfant-Jésus

Québec, Quebec, G1J 1Z4, Canada

Location

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, S7N 4H4, Canada

Location

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

Interventions

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; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 2, 2018
• First Posted: October 5, 2018
• Study Start: December 3, 2018
• Primary Completion: July 21, 2020
• Study Completion: December 20, 2021
• Last Updated: February 15, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (6)