Phase II Randomized Trial of Population PK Dosed Melphalan With Interleukin-6 Blockade With Siltuximab Vesrus BSA Based Melphalan in Patients With Multiple Myeloma Over Age 60 Undergoing Autologous Stem Cell Transplantation

Status: Recruiting
Location: See all (7) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 2
SUMMARY

The purpose of this study is to see if siltuximab plus population pharmacokinetic (PK)-dosed melphalan works as well as the usual approach (body surface area \[BSA\]-dosed melphalan) in people with multiple myeloma (MM) who are receiving an autologous stem cell transplant (ASCT) as part of their standard treatment. The researchers will also see if siltuximab in combination with population PK-dosed melphalan works to decrease symptoms after an ASCT, and will study the safety of siltuximab. For the run-in, 15 patients will receive siltuximab, 11 mg/kg, seven days before and 14 days after autologous hematopoietic stem cell infusion (+/-2 day).

Eligibility
Participation Requirements
Sex: All
Minimum Age: 60
Healthy Volunteers: f
View:

• Histologically-confirmed symptomatic multiple myeloma undergoing autologous HCT with plan off study for melphalan 140 or 200 mg/m2 undergoing HCT within 12 months of diagnosis.

• At least 60 years of age

• Have at least 3 million x 10\^6 CD34+ cells/kg to be infused

• KPS performance status \>60% or ECOG Performance Status score of 0-2

∙ Within 6 weeks prior to enrollment:

• Diffusion capacity \>45% (adjusted for hemoglobin) as predicted by pulmonary function testing.

• LVEF \>45% by MUGA or rest ECHO

• Clinical laboratory values meeting the following criteria

‣ Platelet count ≥ 20 x 10\^9/L

⁃ ALT and AST ≤ 2.5 x ULN o Total bilirubin ≤ 2.5 x ULN; except if the elevation is due to Gilbert's syndrome

⁃ Calculated creatinine clearance \> 40 mL/min

• Before enrollment, all women are expected to be not of childbearing potential as they will be age 60+.

• A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control eg, either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men must also not donate sperm during the study and for 3 months after receiving the last dose of study drug

Locations
United States
New Jersey
Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
RECRUITING
Basking Ridge
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
RECRUITING
Middletown
Memorial Sloan Kettering Bergen (Limited Protocol Activities)
RECRUITING
Montvale
New York
Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)
RECRUITING
Commack
Memorial Sloan Kettering Westchester (Limited Protocol Activities)
RECRUITING
Harrison
Memorial Sloan Kettering Cancer Center (All protocol activities)
RECRUITING
New York
Memorial Sloan Kettering Nassau (Limited Protocol Activities)
RECRUITING
Uniondale
Contact Information
Primary
Gunjan Shah, MD
ABMTTrials@mskcc.org
646-608-3734
Backup
Heather Landau, MD
646-608-3740
Time Frame
Start Date: 2024-11-06
Estimated Completion Date: 2027-11
Participants
Target number of participants: 215
Treatments
Experimental: Siltuximab plus population PK-dosed melphalan
For patients randomized to Arm A, the siltuximab, 11 mg/kg, will be administered seven days before and 14 days after autologous hematopoietic stem cell infusion (+/-2 day). Patients will then receive 70mg/m2 of melphalan on Day -2. The melphalan will be infused over 30 minutes. Six peripheral blood samples of 5 ml in lithium heparin tubes will be collected at 5, 15, 30, 40, 75, and 150 minutes after the end of the melphalan infusion for PK testing. The first four time points are +/- 2 min and the last two time points are +/- 5 minutes. The population PK formula in the Insight Rx software will be used to calculate the melphalan dose for Day -1 to achieve a total target area under the curve (AUC) of 13 mg\*h/L (+/-1.5). The six PK samples will be collected again after the dose on Day -1 to confirm the total AUC. Patients will receive a minimum of the equivalent of 70mg/m2 and a maximum of the equivalent of 260mg/m2.
Active_comparator: Standard BSA-dosed melphalan
Patients randomized to Arm B with received Standard of care (SOC) BSA based melphalan dosing at 140 or 200mg/m2 per treating physician on Day -2 and will not receive the siltuximab. The melphalan will be infused over 30 minutes. Six peripheral blood samples of 5 ml in lithium heparin tubes will be collected at 5, 15, 30, 40, 75, and 150 minutes after the end of the melphalan infusion for PK testing. The first four time points are +/- 2 min and the last two time points are +/- 5 minutes.
Sponsors
Collaborators: RECORDATI GROUP
Leads: Memorial Sloan Kettering Cancer Center

This content was sourced from clinicaltrials.gov