An Open Label, Multicenter, Phase I/II Study of Belantamab Mafodotin in Combination With Kd for the Treatment of Relapsed Myeloma Patients, Refractory to Lenalidomide.

Who is this study for? Patients with Relapsed Multiple Myeloma
What treatments are being studied? Belantamab Mafodotin+Carfilzomib+Dexamethasone
Status: Recruiting
Location: See all (15) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 1/Phase 2
SUMMARY

This is a phase I-II open-label, multicenter, non-randomized study aiming to evaluate the efficacy and safety of belantamab mafodotin in combination with carfilzomib (Kyprolis®) and dexamethasone (Kd). Since this is the first time that this combination is being evaluated in a clinical trial, a first dose escalation part will be developed following the classic 3+3 design, to establish the maximum tolerated dose (MTD) of the combination. Once the MTD will be defined, a dose expansion phase will be open to recruit up to 60 patients. Patients will receive treatment with belantamab-mafodotin + Kd, until unacceptable toxicity, disease progression, patient withdrawal, loss to follow-up, end of study, or death.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

⁃ Participant must be able to understand the study procedures

• Patient is, in the investigator's opinion, willing and able to comply with the protocol requirements.

• Patient has given voluntary written informed consent before performance of any study-related procedure nor part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.

• Relapse multiple myeloma patients that have received at least 1 and no more than 3 prior lines of therapy. Induction, intensification with high-dose melphalan and stem cell transplant and maintenance is considered one line of treatment.

• Patients must be refractory to lenalidomide. Refractoriness is defined as progression while receiving lenalidomide or in the first 60 days after the last dose of lenalidomide.

• Refractoriness would be defined regardless of the dose of lenalidomide received, and the schedule or whether it was given alone or in combination.

• Patients can have received prior treatment with proteasome inhibitors. Patients with prior bortezomib treatment are eligible regardless of refractory status. Prior carfilzomib treatment is allowed, provided that the patients achieve at least a partial response to prior carfilzomib, and that there is a treatment free interval of at least 6 months.

• Participant must have a measurable secretory disease defined as either serum monoclonal protein of ≥ 0,5 g/dl or urine monoclonal (light chain) protein ≥ 200 mg/24 h. For patients whose disease is only measurable by serum FLC, the involved FLC should be ≥ 10mg/L (100 mg/dl), with an abnormal serum FLC ratio.

• Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2

• Participant must be ≥ 18 years of age

• Participant must have adequate organ function. Laboratory values that define adequate organ function for inclusion in study are as follow:

• HEMATOLOGIC Absolute neutrophil count (ANC) ≥1.5 X 109/L Hemoglobin ≥8.0 g/dL (prior red blood cell (RBC) transfusion or recombinant human erythropoietin use is permitted) Platelets ≥75 x 109/L for subjects in whom \<50% of bone marrow nucleated cells are plasma cells; otherwise platelet count \>50 × 10\*9/L (prior platelet transfusion is permitted up to 7 days before the screening phase) Calcium corrected serum calcium \<14 mg/dL (\<3.5 mmol/L); or free ionized calcium \<6.5 mg/dL (\<1.6 mmol/L); HEPATIC Total bilirubin ≤1.5X ULN (Isolated bilirubin ≥1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%) ALT ≤2.5 X ULN AST ≤2.5 X ULN

• RENAL eGFRa ≥40 mL/min/ 1.73 m2 Spot urine (albumin/creatinine ratios) \<500 mg/g (56 mg/mmol) OR Negative/trace (if ≥1+ only eligible if confirmed ≥ 500 mg/g (56 mg/mmol) by albumin/creatinine ratio (spot urine from first void) Urine Dipstick

• CARDIAC LVEF (echo) ≥ 40%

⁃ Female participants: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:

∙ Is not a woman of childbearing potential (WOCBP) OR

‣ Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of \<1% per year), preferably with low user dependency, during the intervention period and for at least 4 months after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention.

⁃ A WOCBP must have a negative highly sensitive serum pregnancy test (as required by local regulations) within 72 hours before the first dose of study intervention.

⁃ The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with a nearly undetected pregnancy.

⁃ Nonchildbearing potential is defined as follows (by other than medical reasons):

‣ ≥45 years of age and has not had menses for \>1 year

‣ Patients who have been amenorrhoeic for \>2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation

‣ Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation.Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure.

⁃ Male participants: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

⁃ Male participants are eligible to participate if they agree to the following from the time of first dose of study until 6 months after the last dose of belantamab mafodotin to allow for clearance of any altered sperm:

⁃ \- Refrain from donating sperm

⁃ PLUS either:

‣ Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR

‣ Must agree to use contraception/barrier as detailed below:

• Agree to use a male condom, even if they have undergone a successful vasectomy and female partner to use an additional highly effective contraceptive method with a failure rate of \<1% per year when having sexual intercourse with a WOCBP (including pregnant females).

⁃ All prior treatment-related toxicities (defined by National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 4.0 must be ≤ Grade 1 at the time of enrolment except for alopecia

⁃ Participant must be able to understand the study procedures and agree to participate in the study by providing written informed consent

Locations
Other Locations
Spain
Hospital Germans Trias i Pujol (ICO BADALONA)
RECRUITING
Badalona
Hospital Clinic
NOT_YET_RECRUITING
Barcelona
ICO Hospitalet
RECRUITING
Bellvitge
H. Gregorio Marañón
NOT_YET_RECRUITING
Madrid
Hospital Universitario 12 de Octubre
NOT_YET_RECRUITING
Madrid
H. Morales Meseguer
RECRUITING
Murcia
HUCA
RECRUITING
Oviedo
H. Son Llatzer
RECRUITING
Palma De Mallorca
Clínica Universidad de Navarra (CUN)
RECRUITING
Pamplona
Hospital Universitario de Salamanca
RECRUITING
Salamanca
H. Universitario de Canarias
NOT_YET_RECRUITING
Santa Cruz De Tenerife
H. Universitario Marqués de Valdecilla
NOT_YET_RECRUITING
Santander
Complejo Hospitalario Santiago (CHUS)
RECRUITING
Santiago De Compostela
Complejo Hospitalario Virgen del Rocío
RECRUITING
Seville
H.U. La Fe
RECRUITING
Valencia
Contact Information
Primary
Carmen López-Carrero
carmen@fundacionpethema.es
0034 699 835 437
Backup
Roberto Maldonado
roberto.maldonado@fundacionpethema.es
0034 683 15 66 87
Time Frame
Start Date: 2021-12-20
Estimated Completion Date: 2028-05-30
Participants
Target number of participants: 60
Treatments
Experimental: Belantamab-Mafodotin + Carfilzomib+ dexametasona
In the phase 1 of the study, aiming to establish the recommended phase 2 dose (RP2D), patients will be included following the classic 3 + 3 design.~Once the DLT assessment period is completed and the MTD is defined, the recruitment will continue in the expansion phase 2.~Combination treatment will be administered at the recommended Phase 2 dose (RP2D) based on the results of the phase 1 dose escalation part of the study:~* Belantamab mafodotin on day 1 at the RP2D, every 8 weeks, intravenously (IV).~* Carfilzomib will be given at the RP2D weekly IV on days: 1, 8, and 15 of every 4-week cycle (Q4W).~* Dexamethasone will be given at the dose of 40 mg (or 20 mg if patient \> 75 years old) on days: 1, 8, 15 and 22 Q4W.~From month 13 onwards carfilzomib treatment will be given on day 1 and 15 of every 4-weeks cycles. Belantamab will be given at the RP2D every 8 weeks and Dexamethasone 40mg on days 1, 8, and 15 of every 4-week cycle.
Related Therapeutic Areas
Sponsors
Leads: PETHEMA Foundation
Collaborators: Adknoma Health Research

This content was sourced from clinicaltrials.gov

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