Study of SubQ Dara With Dose-Attenuated Bortezomib, Lenalidomide, Dexamethasone in Elderly NDMM
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|ClinicalTrials.gov Identifier: NCT04052880|
Recruitment Status : Recruiting
First Posted : August 12, 2019
Last Update Posted : October 29, 2019
|Condition or disease||Intervention/treatment||Phase|
|Newly Diagnosed Multiple Myeloma||Drug: Daratumumab Drug: Bortezomib Drug: Lenalidomide Drug: Dexamethasone Drug: Ixazomib||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||38 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||All subjects will receive initial therapy with 12 cycles of daratumumab in combination with dose-attenuated bortezomib, lenalidomide and dexamethasone (VRd). Maintenance treatment cycles are 28 days in duration with daratumumab and either lenalidomide or ixazomib. The choice of maintenance therapy will be based on cytogenetic risk status at diagnosis. For patients with high-risk MM defined by FISH with t(4;14) only; maintenance therapy will consist of daratumumab with ixazomib. For all other patients, maintenance therapy will consist of daratumumab with lenalidomide. All subjects will continue maintenance treatment until disease progression, except maintenance daratumumab will be discontinued after 2 years if subjects remain on maintenance treatment at that time.|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2 Study of Subcutaneous Daratumumab in Combination With Dose-Attenuated Bortezomib, Lenalidomide, and Dexamethasone in Elderly Newly Diagnosed Multiple Myeloma Patients|
|Actual Study Start Date :||October 24, 2019|
|Estimated Primary Completion Date :||August 2021|
|Estimated Study Completion Date :||December 2021|
Experimental: Daratumumab with dose-attenuated VRd
SubQ Daratumumab with Dose-Attenuated VRd
Daratumumab 1800 mg will be delivered by subcutaneous injection given through a syringe and needle by a manual push over approximately 3 to 5 minutes. Doses will be administered at alternating locations on the abdomen. Daratumumab will be administered weekly during treatment in Cycles 1 to 2, every 2 weeks during cycles 3-6, and every 4 weeks thereafter.
Subjects will receive 1.3 mg/m2 bortezomib as a subcutaneous infusion on Days 1, 8, and 15 during the 28-day cycles.
In Cycles 1 through 12, lenalidomide will be self-administered at a dose of 15 mg orally each day on Days 1 through 21 of each 28-day cycle.
For subjects with CrCl 30-60mL/min, lenalidomide will be reduced to 10mg daily, and for subjects with CrCl 15-30 mL/min, lenalidomide will be reduced to 5mg daily.
In maintenance phase: lenalidomide will be administered at one dose level below Cycles 1-12 dosing ie 10 mg orally daily.
In maintenance, for subjects with CrCl 30-60 mL/min, lenalidomide will be reduced to 5 mg daily during maintenance treatment, and for subjects with CrCl 15-30 mL/min, lenalidomide will be reduced to 5 mg every other day during maintenance treatment.
Dexamethasone will be self-administered orally at a total dose of 20 mg weekly during cycles.
However, the dexamethasone 20 mg oral or IV (only if oral is not available) dose administered as a preinfusion medication on daratumumab infusion days replaces the oral dexamethasone dose for that day. Dexamethasone will be administered until the subject experiences disease progression or unacceptable toxicity.
In the maintenance phase, dexamethasone/steroid premedications may be tapered or discontinued in the absence of daratumumab related infusion reactions/based on patient tolerance. In the event of persistent daratumumab related infusion reactions, the least amount of steroid premedications needed to prevent the same may be used.
During maintenance treatment, if choice of maintenance therapy includes ixazomib, ixazomib will be administered at 3 mg orally daily on Days 1,8, and 15 of each cycle. For subjects with CrCl 15-30 mL/min, ixazomib will be reduced to 2.3 mg once per week during maintenance treatment.
- Responses: VGPR or better [ Time Frame: At the end of cycle 8, each cycle is 28 days ]≥ VGPR rate after 8 cycles of therapy, defined as the proportion of subjects who have achieved VGPR or better, according to the IMWG criteria.
- Overall Response Rates [ Time Frame: Within a year ]ORR (≥PR), CBR (≥SD), ≥CR, and sCR rates defined as the proportion of subjects who achieve each of these response categories (or better response category) according to the IMWG criteria
- Duration of ORR (≥PR), ≥VGPR, ≥CR, and sCR [ Time Frame: Within two years ]Defined as the duration from the date of initial attainment of a response category (or better response category), according to the IMWG criteria, to the date of first documented evidence of relapse from CR (or sCR) or progressive disease (PD)
- Time to Overall Response Rate [ Time Frame: Within a year ]Defined as the duration from the date of initial therapy to the date of attainment of a response category and was subsequently confirmed by a repeated measurement as required by the IMWG criteria
- Time to Progression [ Time Frame: Within 2 years ]Defined as the duration from the date of initial therapy to the date of first documented evidence of progressive disease according to the IMWG criteria
- Progression Free Survival [ Time Frame: Within 5 years ]Defined as the duration from the date of initial therapy to the date of first documented evidence of PD or death, whichever comes first
- Overall Survival [ Time Frame: Within 5 years ]Defined as the duration from the date of initial therapy to the date of the subject's death.
- Number of Adverse Events [ Time Frame: Within 5 years ]To assess safety and tolerability using the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE Version 4.03)
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): NCT04052880
|Contact: Ajai Chari, MDemail@example.com|
|Contact: Lisa La, MSfirstname.lastname@example.org|
|United States, New York|
|Icahn School of Medicine at Mount Sinai||Recruiting|
|New York, New York, United States, 10029|
|Contact: Lisa La, MS 212-241-8615 email@example.com|
|Contact: Katarzyna Zarychta, MS 212-241-2495 firstname.lastname@example.org|
|Principal Investigator: Ajai Chari, MD|
|Principal Investigator:||Ajai Chari, MD||Icahn School of Medicine at Mount Sinai|
|Study Director:||Sundar Jagannath, MBBS||Icahn School of Medicine at Mount Sinai|