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Trial record 1 of 1 for:    GEM-BELA-VRd
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Belantamab Mafodotin in Newly Diagnosed Transplant Eligible Multiple Myeloma Patients

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ClinicalTrials.gov Identifier: NCT04802356
Recruitment Status : Recruiting
First Posted : March 17, 2021
Last Update Posted : December 6, 2021
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
PETHEMA Foundation

Brief Summary:

This is a multicenter, open label clinical trial evaluating the safety of the combination of belantamab mafodotin + the combination treatment VRd (bortezomib, lenalidomide, dexamethasone) in newly diagnosed (ND) transplant eligible multiple myeloma (MM) patients.

Eligible patients will be included in the study and they will receive three induction cycles with belantamab mafodotin (8-week cycles) and six induction cycles with VRd (4-week cycles). Immediately after the fourth VRd cycle, and in the absence of progression or unacceptable toxicity, mobilization of hematopoietic stem cells with G-CSF and subsequent apheresis will take place. Then, patients will receive one additional induction cycle with belantamab mafodotin (8-week cycle) and two additional induction cycles with VRd (4-week cycles) followed by intensification with high-dose melphalan (200mg/m2) and the autologous stem cell transplant. Three months after transplantation, and as long as clinical and hematological conditions allow, patients will receive one cycle of consolidation with belantamab mafodotin (8-week cycle) and two additional cycles of consolidation with VRd (4-week cycles) at the same doses as during induction and, subsequently, patients will receive maintenance treatment with lenalidomide (continuously until disease progression, patient withdrawal, unacceptable toxicity, loss to follow up, end of study or death) and belantamab mafodotin (for 2 years).


Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Belantamab mafodotin Drug: Bortezomib Drug: Lenalidomide Drug: Dexamethasone Procedure: Autologous stem cell transplant (ASCT) Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: This is a multicenter, open label, non-randomized single arm clinical trial
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Label, Multicenter, Phase II Study of Belantamab Mafodotin in Combination With VRd for the Treatment of Newly Diagnosed Transplant Eligible Multiple Myeloma Patients
Actual Study Start Date : April 7, 2021
Estimated Primary Completion Date : March 2025
Estimated Study Completion Date : July 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma
Drug Information available for: Belantamab

Arm Intervention/treatment
Experimental: Multiple Myeloma experimental arm
Combination of belantamab mafodotin + the combination treatment VRd (bortezomib, lenalidomide, dexamethasone)
Drug: Belantamab mafodotin

Dose of 2.5 mg/kg/every 8 weeks on day 1, intravenously, Induction: three induction cycles with belantamab mafodotin in combination with VRd.

Consolidation: one cycle after 90 days of transplantation with belantamab mafodotin in combination with VRd.

Maintenance: belantamab mafodotin in combination with lenalidomide until disease progression, patients withdrawal, death or up to two years, whichever occurs first

Other Name: Blenrep

Drug: Bortezomib
Dose of 1.3 mg/m2, on days: 1, 4, 8 and 11 of every 28-day cycle. Subcutaneous administration Induction: 6 cycles Consolidation: 2 cycles

Drug: Lenalidomide
Dose of 25 mg/day on days 1-21 of every 28-day cycle. Oral administration. Induction: 6 cycles Consolidation: 2 cycles Maintenance: 10 mg/day on days 1-21 continuously (may increase up to 15 mg/day) until disease progression, patients withdrawal, death, whichever occurs first

Drug: Dexamethasone
Dose of 20 mg on days: 1, 2, 4, 5, 8, 9, 11 and 12 of every 28-day cycle. Oral administration Induction: 6 cycles Consolidation: 2 cycles

Procedure: Autologous stem cell transplant (ASCT)
High-dose melphalan (200 mg/m2) and ASCT will be performed as per routine practice




Primary Outcome Measures :
  1. Incidence of deaths [ Time Frame: Throughout the study period. Approximately 48 months ]
    Number of patients that are exitus after start of the study treatment

  2. Incidence of adverse events (AEs) [ Time Frame: Throughout the study period. Approximately 48 months ]
    Number of patients experiencing AEs, either treatment or non-treatment related, classified according to severity and graded according to NCTCAE V4.0

  3. Incidence of analytical alterations [ Time Frame: Throughout the study period. Approximately 48 months ]
    Changes in laboratory analytes from the hematology and blood chemistry panel after start of the study experimental treatment

  4. Incidence of ocular events [ Time Frame: Throughout the study period. Approximately 48 months ]
    Number of patients experiencing ocular alterations after start of the study experimental treatment.


Secondary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: Throughout the study period. Approximately 48 months ]
    The percentage of participants with a confirmed partial response (PR) or better (PR, Very good partial response (VGPR), Complete response (CR), stringent complete response (sCR)). Assessed Q4W during induction, three months after ASCT, after consolidation, q4W during maintenance until PD, unacceptable toxicity, death, withdrawal of consent, loss to follow-up or end of the study.

  2. Complete Response Rate (CRR) [ Time Frame: Throughout the study period. Approximately 48 months ]
    The percentage of participants with a confirmed complete response (CR) or better (stringent complete response (CR, sCR)). Assessed Q4W during induction, three months after ASCT, after consolidation, q4W during maintenance until PD, unacceptable toxicity, death, withdrawal of consent, loss to follow-up or end of the study.

  3. Minimal Residual Disease (MRD) negativity rate [ Time Frame: Throughout the study period. Approximately 48 months ]
    The percentage of participants who are MRD negative by next-generation flow cytometry (NGF). MRD will be evaluated after each phase of treatment (induction, autologous stem cell transplant, consolidation and once a year during maintenance). If there is suspect of CR at any time different of those previously specified, the MRD should be evaluated at the suspicion of CR. Assessed Q4W during induction, three months after ASCT, after consolidation, q4W during maintenance until PD, unacceptable toxicity, death, withdrawal of consent, loss to follow-up or end of the study.

  4. Time to Response (TTR) [ Time Frame: Throughout the study period. Approximately 48 months ]
    The time from the date of inclusion and the first documented evidence of response (PR or better) among participants who achieve confirmed PR or better.

  5. Duration of Response (DoR) [ Time Frame: Throughout the study period. Approximately 48 months ]
    The time from first documented evidence of PR or better until progressive disease (PD) or death due to PD among participants who achieved PR or better.

  6. Progression-Free Survival (PFS) [ Time Frame: Throughout the study period. Approximately 48 months ]
    The time from the date of inclusion until the earliest date of documented disease progression or death due to any cause.

  7. Progression-Free Survival 2 (PFS2) [ Time Frame: Throughout the study period. Approximately 48 months ]
    The time from inclusion to disease progression after initiation of new anti-cancer therapy or death from any cause, whichever is earlier. If disease progression after new anti-cancer therapy cannot be measured, a PFS event is defined as the date of discontinuation of new anti-cancer therapy, or death from any cause, whichever is earlier.

  8. Overall Survival (OS) [ Time Frame: Throughout the study period. Approximately 48 months ]
    Defined as the time from the date of inclusion until the date of death due to any cause.

  9. Efficiency of hematopoietic stem cell collection [ Time Frame: After cycle 4 of induction, 4 months after inclusion. ]
    Number of CD34 cells collected after 2 induction cycles of treatment of belantamab mafodotin + 4 induction cycles of treatment of VRd.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Participant must have Newly diagnosed multiple myeloma. Newly diagnosed subjects must have symptomatic disease following the IMWG updated criteria (Rajkumar Lancet 2014, Appendix 6).
  2. Participant must have a measurable secretory disease defined as either serum monoclonal protein of ≥ 0,5 g/dl or urine monoclonal (light chain) protein ≥ 200mg/24h.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.
  3. Newly diagnosed participants must be eligible for stem cell transplant at investigator criteria.
  4. Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
  5. Participant must be ≥ 18 years of age
  6. Participant must have adequate organ function, defined as follows:

    System Laboratory Values 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); 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 ≥30 mL/min/ 1.73 m2 Spot urine (albumin/creatinine ratios (spot urine) <500 mg/g (56 mg/mmol)

  7. 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 and agree to use a highly effective method of contraception during the study and for 4 months after the last dose of belantamab mafodotin. Additional requirements for pregnancy testing during and after 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.
  8. 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 for at least 6 months:

    • 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 4.0 (must be ≤ Grade 1 at the time of enrolment except for alopecia).

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

Exclusion Criteria:

Patients that present any of the following exclusion criteria cannot be included in the trial:

  1. 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.
  2. 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.
  3. Participant has meningeal involvement of multiple myeloma.
  4. Pregnant or breastfeeding females.
  5. Participant is simultaneously enrolled in other interventional clinical trial.
  6. Participant must has used an investigational drug within 14 days or five half-lives, whichever is shorter, preceding the first dose of study drug.
  7. 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.
  8. Participant who have received prior treatment with a monoclonal antibody within 30 days of receiving the first dose of study drugs.
  9. Participant has a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to: belantamab mafodotin, lenalidomide, boronic acid (bortezomib), dexamethasone or any of the components of the study treatment.
  10. Participant who have had major surgery ≤ 4 weeks prior to initiating protocol therapy.
  11. Participant who have current corneal epithelial disease except mild punctate keratopathy
  12. Participant has peripheral neuropathy or neuropathic pain grade ≥2, as defined by the National Cancer Institute Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0 (APPENDIX 4).
  13. Participant is unable or unwilling to undergone antithrombotic prophylactic treatment
  14. Participant evidence of cardiovascular risk including any of the following:

    • Evidence of current clinically significant uncontrolled 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
  15. Incidence of gastrointestinal disease that may significantly alter the absorption of Lenalidomide.
  16. 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
  17. 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
  18. Participant who use contact lenses while participating in this study, except if contact lenses are removed during participation in the study
  19. Participant who have had plasmapheresis within 7 days prior to first dose of study treatment.
  20. Evidence of active mucosal or internal bleeding.
  21. Any serious medical condition or psychiatric illness that would interfere in understanding of the informed consent form.
  22. 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).
  23. Patients with acute diffuse infiltrative pulmonary disease and/or pericardial disease.
  24. Patients with severe chronic obstructive pulmonary disease (COPD) or asthma with forced expiratory volume in the first minute (FEV1) less than 50%.
  25. 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 a positive test for the surface antigen of hepatitis C [HCsAg] or positive quantification of HCV RNA 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.


Information from the National Library of Medicine

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): NCT04802356


Contacts
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Contact: Carmen López-Carrero 0034 699 835 437 carmen@fundacionpethema.es
Contact: Roberto Maldonado 0034 683 15 66 87 roberto.maldonado@fundacionpethema.es

Locations
Show Show 18 study locations
Sponsors and Collaborators
PETHEMA Foundation
GlaxoSmithKline
Investigators
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Study Chair: Maria Victoria Mateos Manteca, M.D.; Ph.D. Hospital Universitario de Salamanca (Salamanca)
Study Chair: Jesus San Miguel Izquierdo, M.D.; Ph.D. Clínica Universidad de Navarra (Pamplona)
Publications:

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Responsible Party: PETHEMA Foundation
ClinicalTrials.gov Identifier: NCT04802356    
Other Study ID Numbers: GEM-BELA-VRd
2020-002050-24 ( EudraCT Number )
First Posted: March 17, 2021    Key Record Dates
Last Update Posted: December 6, 2021
Last Verified: December 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by PETHEMA Foundation:
NEWLY DIAGNOSED
TRANSPLANT ELEGIBLE
BELANTAMAB MAFODOTIN
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
Lenalidomide
Bortezomib
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Immunologic Factors
Angiogenesis Inhibitors