Phase II Multicenter Study of Belantamab Mafodotin with VRd in Newly Diagnosed Transplant-Eligible Multiple Myeloma Patients
- Trial ID
- 2024-516130-35-00
- Protocol
- GEM-BELA-VRd
- Sponsor
- Fundacion PETHEMA
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **safety** and tolerability of belantamab mafodotin when administered in combination with VRd (bortezomib, lenalidomide, and dexamethasone) in patients with newly diagnosed, transplant-eligible multiple myeloma. This is clinically relevant as it aims to determine the potential risks and adverse effects associated with this combination therapy, which is crucial for ensuring patient safety and optimizing treatment protocols.
Secondary objectives include:
- Assessing the efficacy of belantamab mafodotin in combination with VRd in terms of efficacy outcomes in participants with newly diagnosed multiple myeloma who are transplant eligible.
- Evaluating the efficiency of collection of CD34 cells after two induction cycles of belantamab mafodotin and four induction cycles with VRd.
Participants
The clinical trial involves participants diagnosed with **multiple myeloma**, specifically those who are newly diagnosed and eligible for stem cell transplant. The study population includes both male and female subjects aged 18 years and older. Participants must have a measurable secretory disease and meet specific health criteria, such as an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less and adequate organ function. The trial does not specify the total number of participants, as this information was not provided by the sponsor. Participants are required to adhere to contraceptive guidelines consistent with local regulations, and lifestyle considerations such as diet and physical activity are not explicitly mentioned. The trial includes a vulnerable population, and participants must provide written informed consent to partake in the study.
Plans and Procedures
The clinical trial is designed as an open-label, multicenter, phase II study to evaluate the safety and tolerability of **belantamab mafodotin** in combination with VRd (bortezomib, lenalidomide, and dexamethasone) for the treatment of newly diagnosed, transplant-eligible patients with **multiple myeloma**. The trial is not randomized or double-blind, allowing for direct observation of the treatment effects. The estimated duration of the trial is from April 26, 2021, to May 31, 2025, encompassing a comprehensive evaluation period.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, performance status, and organ function. The primary inclusion criteria require participants to have newly diagnosed symptomatic multiple myeloma, measurable secretory disease, and eligibility for stem cell transplant. The study will include six treatment cycles during the induction therapy phase, with follow-up visits scheduled to monitor adverse events, hematology, and clinical chemistry parameters. The end-of-study visit will assess the overall response and progression-free survival.
The expected length of participant involvement is up to 36 months, depending on individual response and tolerability. Conditions that may lead to early termination from the study include the occurrence of unacceptable adverse events, disease progression, or withdrawal of consent. Participants will be monitored for adverse events, changes in hematology and clinical chemistry parameters, and ocular findings throughout the study. The trial aims to provide valuable insights into the efficacy and safety of the treatment regimen for multiple myeloma patients.
Treatment
The clinical trial involves the administration of several experimental medications, each with specific pharmaceutical forms, dosages, and routes of administration. **Lenalidomide Biocon 10 mg hard capsules** are administered orally. The maximum daily dose is 25 mg, with a total treatment period of up to 36 weeks. The active substance, **lenalidomide**, is of chemical origin and is provided by BIOCON PHARMA MALTA I LIMITED. The capsules are not formulated for pediatric use.
**Lenalidomide Biocon 15 mg hard capsules** are also administered orally, with the same maximum daily dose and treatment period as the 10 mg capsules. The active substance remains **lenalidomide**, and the formulation is identical in terms of origin and provider.
**Lenalidomide 25 mg hard capsules** are similarly administered orally, with a maximum daily dose of 25 mg and a treatment period of 36 weeks. The active substance is **lenalidomide**, provided by WOCKHARDT UK LTD, and is of chemical origin.
**Belantamab mafodotin** is provided as a powder for solution for injection, administered intravenously. The maximum daily dose is 100 mg/kg, with a treatment period of up to 32 weeks. This protein-based substance is supplied by GLAXOSMITHKLINE and is classified as an antineoplastic agent, specifically a monoclonal antibody.
**Melphalan Tillomed 50 mg powder and solvent for solution for injection/infusion** is administered via intravenous injection. The maximum daily dose is 200 mg, with a treatment period of 36 weeks. The active substance, **melphalan**, is of chemical origin and provided by TILLOMED PHARMA GMBH. It is a bifunctional alkylating antineoplastic agent with immunosuppressive properties.
**Dexamethasone 20 mg tablets** are administered orally, with a maximum daily dose of 20 mg and a treatment period of 8 weeks. The active substance, **dexamethasone**, is of chemical origin and provided by KRKA, D.D., NOVO MESTO. It is classified as a corticosteroid.
**Bortezomib Biotech Pharma Limited 3.5 mg powder for solution for injection** is administered via subcutaneous injection. The maximum daily dose is 1.3 mg/m², with a treatment period of 8 weeks. The active substance, **bortezomib**, is of chemical origin and provided by BIO TECH PHARMA LIMITED. It functions as a proteasomal inhibitor.
Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed treatment regimens. The trial does not include any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments.
Efficacy
The efficacy of the clinical trial will be assessed using a combination of primary and secondary endpoints. Primary endpoints include the number of participants with adverse events during the induction therapy, changes from baseline in hematology parameters such as absolute white blood cell count, basophils, eosinophils, lymphocytes, monocytes, platelet count, and neutrophils, as well as changes in clinical chemistry parameters including Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), and others. Additionally, the number of participants with abnormal ocular findings and symptomatic adverse effects measured by the Ocular Surface Disease Index (OSDI) will be evaluated during the six treatment cycles.
Secondary endpoints will focus on the Complete Response Rate (CRR), Progression-free survival (PFS), PFS2, Overall survival (OS), Overall response rate (ORR), Duration of response (DoR), Time to response (TTR), Time to progression (TTP), and the rate of Minimal Residual Disease (MRD) negativity. These parameters will be measured and analyzed according to the International Myeloma Working Group (IMWG) Response Criteria. The trial will utilize validated scales and laboratory tests to ensure accurate and reliable data collection throughout the study period.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Participant must have Newly diagnosed multiple myeloma. Newly diagnosed subjects must have symptomatic disease following the IMWG updated criteria (Rajkumar Lancet 2014, Appendix 6).
- 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 ≥ 100mg/L (10 mg/dl), with an abnormal serum free light chain ratio (<0.26 or >1.65)ratio.
- Newly diagnosed participants must be eligible for stem cell transplant at investigator criteria.
- 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, defined as follows: System Hematologic*: Absolute neutrophil count (ANC):≥1.5 X 109/L, Hemoglobin: ≥8.0 g/dL, Platelets: ≥75 x 109/L for subjects in whom <50% of bone marrow nucleated cells are plasma cells; otherwise platelet count >50 × 109/L, Calcium: corrected serum calcium <14 mg/dL (<3.5 mmol/L); or free ionized calcium <6.5 mg/dL (<1.6 mmol/L); System Hepatic: Total bilirubin: ≤1.5X ULN (Isolated bilirubin > 1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%), ALT ≤2.5 X ULN, AST ≤2.5 X ULN; System Renal: eGFRa: ≥30 mL/min/ 1.73 m2, Spot urine (albumin/creatinine ratios (spot urine) ACR: <500 mg/g (56 mg/mmol) or Urine dipstick- Negative/trace (if ≥1+ only eligible if confirmed ≤500 mg/g (56 mg/mmol) by albumin/creatinine ratio (spot urine from first void) <500 mg/g (56 mg/mmol) * Without growth factor support, blood transfusion or platelet stimulating agents for the past 14 days, excluding erythropoietin.
- 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. In this case, 2 blood tests will be. The first pregnancy test must be performed within 10 to 14 days prior to the start of treatment and the second pregnancy test must be performed within 24 hours prior to the start of treatment. After, pregnancy testThe pregnancy tests must be negative throughout the study (every week for the first 4 weeks, after that, before to receive study treatments. A urine or blood test can be used during the rest of the study. A WOCBP must agree to use a highly effective method of contraception during the study and for 4 months after the last dose of belantamab mafodotin. 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 during the intervention period and 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 and female partner to use an additional highly effective contraceptive method with a failure rate of <1% per year as when having sexual intercourse with a woman of childbearing potential (including pregnant females). All prior treatment-related toxicities (defined by National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 5.0 (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.
Exclusion Criteria
- Participant has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), plasma cell leukemia or active POEMS syndrome at the time of screening.
- Participant who have had major surgery ≤ 4 weeks prior to initiating protocol therapy.
- Participant who have current corneal epithelial disease except mild punctate keratopathy
- Participant has peripheral neuropathy or neuropathic pain grade ≥2, as defined by the National Cancer Institute Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0 (APPENDIX 4).
- Participant is unable or unwilling to undergone antithrombotic prophylactic treatment
- Participant evidence of cardiovascular risk including any of the following: ● Evidence of current clinically significant uncontrolled/untreated arrhythmias, including clinically significant ECG abnormalities such as 2nd degree (Type II) or 3rd degree atrioventricular (AV) block. ● History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within three months of Screening. ● Class III or IV heart failure as defined by the New York Heart Association functional classification system [NYHA, 1994] ● Uncontrolled hypertension
- Incidence of gastrointestinal disease that may significantly alter the absorption of Lenalidomide.
- Participant must not have current unstable liver or biliary disease defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. Note: Stable chronic liver disease (including Gilbert’s syndrome or asymptomatic gallstones) or hepatobiliary involvement of malignancy is acceptable if otherwise meets entry criteria
- Presence of active renal condition (infection, requirement for dialysis or any other condition that could affect patient’s safety). Participants with isolated proteinuria resulting from MM are eligible, provided they fulfil inclusion criteria
- Participant who use contact lenses while participating in this study, except if contact lenses are removed during participation in the study
- Participant who have had plasmapheresis within 7 days prior to first dose of study treatment.
- Participant has malignancies other than disease under study, except for any other malignancy from which the participant has been disease-free for more than 2 years and, in the opinion of the principal investigators, will not affect the evaluation of the effects of this clinical trial treatment on the currently targeted malignancy. Participants with curatively treated non-melanoma skin cancer may be enrolled.
- Evidence of active mucosal or internal bleeding.
- Any serious medical condition or psychiatric illness that would interfere in understanding of the informed consent form.
- Uncontrolled endocrine diseases (i.e. diabetes mellitus, hypothyroidism or hyperthyroidism) (i.e. requiring relevant changes in medication within the last month, or hospital admission within the last 3 months).
- Patients with acute diffuse infiltrative pulmonary disease and/or pericardial disease.
- Patients with severe chronic obstructive pulmonary disease (COPD) or asthma with forced expiratory volume in the first minute (FEV1) less than 50%.
- The subject is seropositive for human immunodeficiency virus (HIV) or presence of active hepatitis B infection (documented by a positive test for hepatitis B surface antigen [HBsAg], or hepatitis C (documented by Positive hepatitis C antibody test result or positive quantification of HCV RNA). Note: presence of Hep B surface antibody (HBsAb) indicating previous vaccination will not exclude a participant. Presence of HbcAb with negative hepatitis B PCR will not exclude and then, appropriate prophylaxis should be administered to avoid virus reactivation. If patients with HbcAb with negative hep B PCR included, it is necessary to do HBV- DNA testing prior to the start of study treatment and subsequently every 3 months, or if LFT elevations requiring increased monitoring or stopping criteria occur, or for any clinical suspicion of hepatitis reactivation Note: Participants with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained. Note: Hepatitis RNA testing is optional and participants with negative Hepatitis C antibody test are not required to also undergo Hepatitis C RNA testing.
- Participant has meningeal involvement of multiple myeloma.
- Pregnant or breastfeeding females.
- Participant is simultaneously enrolled in other interventional clinical trials.
- Participant must have used an investigational drug within 14 days or five half-lives, whichever is shorter, preceding the first dose of study drug.
- Participant has used of any anti-myeloma drug therapy, except for steroid pulses in case of emergency (40 mg of dexamethasone for 4 days), the administration of bisphosphonates or antialgic radiotherapy or due to the presence of plasmacytomas requiring some emergency.
- Participant who has received prior treatment with a monoclonal antibody within 30 days of receiving the first dose of study drugs. Note: Monoclonal antibodies used for serious conditions unrelated to MM, such as COVID, may be permitted but need to be discussed with the MD.
- Participant has a known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to drugs chemically related to belantamab mafodotin, or any other components of the study treatment.
- Active infection requiring treatment
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Spain | Not Recruiting | 26 Apr 2021 | 50 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Lenalidomide Biocon 10 mg harde capsules | Test | HARDE CAPSULES | ORAL | 25 | 36 | PRD10148084 |
Lenalidomide Biocon 15 mg harde capsules | Test | HARDE CAPSULES | ORAL | 25 | 36 | PRD10148089 |
Melphalan Tillomed 50 mg powder and solvent for solution for injection/infusion | Test | POWDER AND SOLVENT FOR SOLUTION FOR INJECTION/INFUSION | INTRAVENOUS INJECTION | 200 | 36 | PRD7929510 |
Lenalidomide 25mg hard capsules | Test | HARD CAPSULES | ORAL | 25 | 36 | PRD10184466 |
Dexamethasone 20 mg tablets | Test | TABLETS | ORAL | 20 | 8 | PRD4715842 |
Bortezomib Biotech Pharma Limited 3.5 mg powder for solution for injection | Test | POWDER FOR SOLUTION FOR INJECTION | SUBCUTANEOUS INJECTION | 1.3 | 8 | PRD10598160 |