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Belantamab Mafodotin, Lenalidomide, and Daratumumab for the Treatment of Relapsed, Refractory, or Previously Untreated Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT04892264
Recruitment Status : Recruiting
First Posted : May 19, 2021
Last Update Posted : June 13, 2022
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

Brief Summary:
This phase I/II trial studies the best dose and effect of belantamab mafodotin given together with lenalidomide and daratumumab in treating patients with multiple myeloma that has come back (relapsed), does not respond to treatment (refractory) or for which the patient has not received treatment in the past (previously untreated). Belantamab mafodotin is a monoclonal antibody, called belantamab, linked to a chemotherapy drug, called mafodotin. Belantamab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as BCMA receptors, and delivers mafodotin to kill them. Lenalidomide is an immunomodulatory drug (altering the immune effects on the tumor cell). Daratumumab is a drug that is a monoclonal antibody that is directed towards a protein on the myeloma cell. Giving belantamab mafodotin together with lenalidomide and daratumumab may kill more cancer cells.

Condition or disease Intervention/treatment Phase
Plasma Cell Myeloma Recurrent Plasma Cell Myeloma Refractory Plasma Cell Myeloma Biological: Belantamab Mafodotin Biological: Daratumumab Drug: Dexamethasone Drug: Lenalidomide Other: Quality-of-Life Assessment Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Phase 1 / 2 Trial of Belantamab Mafodotin, Lenalidomide, and Daratumumab in Relapsed or Newly Diagnosed Multiple Myeloma Patients
Actual Study Start Date : June 4, 2021
Estimated Primary Completion Date : May 15, 2025
Estimated Study Completion Date : May 15, 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: Arm A (belantamab mafodotin, lenalidomide, daratumumab)

INDUCTION: Patients receive belantamab mafodotin IV over 30 minutes on day 1 of odd number cycles, lenalidomide PO QD on days 1-21, and daratumumab IV over 90 minutes on days 1, 8, 15, and 22 of cycles 1 and 2, days 1 and 15 of cycles 3-6, and day 1 of subsequent cycles. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Beginning cycle 13, patients receive belantamab mafodotin IV over 30 minutes on day 1 of odd number cycles (starting cycle 13), lenalidomide PO QD on days 1-21, and daratumumab IV over 90 minutes on day 1. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

Biological: Belantamab Mafodotin
Given IV
Other Names:
  • Belantamab Mafodotin-blmf
  • Blenrep
  • GSK2857916
  • J6M0-mcMMAF

Biological: Daratumumab
Given IV
Other Names:
  • Anti-CD38 Monoclonal Antibody
  • Darzalex
  • HuMax-CD38
  • JNJ-54767414

Drug: Lenalidomide
Given PO
Other Names:
  • CC-5013
  • CC5013
  • CDC 501
  • Revlimid

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Experimental: Arm B (belantamab mafodotin, lenalidomide, daratumumab, Dxevo)

INDUCTION: Patients receive belantamab mafodotin IV over 30 minutes on day 1 of cycles 2, 4, 6, 8, 10, and 12, lenalidomide PO QD on days 1-21, daratumumab IV over 90 minutes on days 1, 8, 15, and 22 of cycles 1 and 3, and days 1 and 15 on cycles 5, 7, 9, and 11. Patients also receive dexamethasone PO on days 1, 8, 15 and 22. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Beginning cycle 13, patients receive belantamab mafodotin IV over 30 minutes on day 1 of even numbered cycles, lenalidomide PO QD on days 1-21, and daratumumab IV over 90 minutes on day 1 of odd numbered cycles. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

Biological: Belantamab Mafodotin
Given IV
Other Names:
  • Belantamab Mafodotin-blmf
  • Blenrep
  • GSK2857916
  • J6M0-mcMMAF

Biological: Daratumumab
Given IV
Other Names:
  • Anti-CD38 Monoclonal Antibody
  • Darzalex
  • HuMax-CD38
  • JNJ-54767414

Drug: Dexamethasone
Given PO
Other Names:
  • Aacidexam
  • Adexone
  • Aknichthol Dexa
  • Alba-Dex
  • Alin
  • Alin Depot
  • Alin Oftalmico
  • Amplidermis
  • Anemul mono
  • Auricularum
  • Auxiloson
  • Baycadron
  • Baycuten
  • Baycuten N
  • Cortidexason
  • Cortisumman
  • Decacort
  • Decadrol
  • Decadron
  • Decadron DP
  • Decalix
  • Decameth
  • Decasone R.p.
  • Dectancyl
  • Dekacort
  • Deltafluorene
  • Deronil
  • Desamethasone
  • Desameton
  • Dexa-Mamallet
  • Dexa-Rhinosan
  • Dexa-Scheroson
  • Dexa-sine
  • Dexacortal
  • Dexacortin
  • Dexafarma
  • Dexafluorene
  • Dexalocal
  • Dexamecortin
  • Dexameth
  • Dexamethasone Intensol
  • Dexamethasonum
  • Dexamonozon
  • Dexapos
  • Dexinoral
  • Dexone
  • Dinormon
  • Dxevo
  • Fluorodelta
  • Fortecortin
  • Gammacorten
  • Hemady
  • Hexadecadrol
  • Hexadrol
  • Lokalison-F
  • Loverine
  • Methylfluorprednisolone
  • Millicorten
  • Mymethasone
  • Orgadrone
  • Spersadex
  • TaperDex
  • Visumetazone
  • ZoDex

Drug: Lenalidomide
Given PO
Other Names:
  • CC-5013
  • CC5013
  • CDC 501
  • Revlimid

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment




Primary Outcome Measures :
  1. Maximum tolerated dose (MTD) of belantamab in combination with daratumumab and lenalidomide in patients with relapsed and/or refractory multiple myeloma (Phase I) [ Time Frame: Up to 28 days ]
    The MTD will be determined by the dose limiting toxicities (DLTs) seen in cycle 1 of the therapy in the phase I portion. The phase II portion will be based on the determined MTD. MTD is defined as the dose level below the lowest dose that induces dose limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients).

  2. Complete response rate with belantamab, daratumumab, and lenalidomide, OR alternating cycles of daratumumab, lenalidomide, dexamethasone and belantamab, lenalidomide and dexamethasone, when used as initial therapy (Phase II) [ Time Frame: Up to 336 days (induction therapy cycles 1-12/each cycle 28 days) ]
    A confirmed response is defined as a patient who has achieved a stringent complete response (sCR) or CR (as defined by the International Myeloma Working Group criteria) and maintained it on two consecutive evaluations at least 2 weeks apart.


Secondary Outcome Measures :
  1. Incidence of toxicity (Phase I) [ Time Frame: Up to 3 years ]
    Defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment. Non-hematologic toxicities will be evaluated via the ordinal Common Terminology Criteria (CTC) standard toxicity grading. Hematologic toxicity measures of thrombocytopenia, neutropenia, and leukopenia will be assessed using continuous variables as the outcome measures (primarily nadir) as well as categorization via CTC standard toxicity grading. Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.

  2. Overall response rate [ Time Frame: Up to 3 years ]
    Will be estimated by the number of patients with each response category (e.g: sCR, CR, VGPR, partial response [PR], etc) divided by the total number of evaluable patients.

  3. Greater than or equal to very good partial response (VGPR) rate [ Time Frame: Up to 3 years ]
    Will be estimated by the number of patients with each response category (e.g: sCR, CR, VGPR, PR, etc) divided by the total number of evaluable patients.

  4. Overall survival [ Time Frame: From registration to death due to any cause, assessed up to 3 years ]
    Will be estimated using the method of Kaplan-Meier.

  5. Progression-free survival [ Time Frame: From registration to the earliest date of documentation of disease progression or relapse or death due to any cause, assessed up to 3 years ]
    Will be estimated using the method of Kaplan-Meier.

  6. Time to response [ Time Frame: Time between the date of first dose and the first documented evidence of a partial response or better, assessed up to 3 years ]
    Descriptive statistics will be estimated.

  7. Incidence of adverse events [ Time Frame: Up to 30 days post treatment ]
    The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.



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:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age >= 18 years
  • Phase I: Relapsed or refractory multiple myeloma with at least one prior line of therapy that includes a proteasome inhibitor and an immunomodulatory drug. Patient should be refractory to lenalidomide
  • Phase II: Previously untreated multiple myeloma (diagnosed by International Myeloma Working Group [IMWG] criteria) or have received no more than one cycle of Standard of Care treatment regimen
  • Note: Prior radiation therapy for the treatment of solitary plasmacytoma is permitted. Prior therapy with clarithromycin, dehydroepiandrosterone (DHEA), anakinra, pamidronate or zoledronic acid is permitted. Any additional agents not listed must be approved by the principal investigator
  • Measurable disease

    • Note: Phase I patients can enter trial with M spike >= 0.5 g/dl
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
  • Hemoglobin >= 9.0 g/dL (obtained =< 14 days prior to registration)
  • Absolute neutrophil count (ANC) >= 1200/mm^3 (obtained =< 14 days prior to registration)
  • Platelet count >= 100,000/mm^3 (obtained =< 14 days prior to registration)
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) (obtained =< 14 days prior to registration)
  • Alanine aminotransferase (ALT) and aspartate transaminase (AST) =< 2.5 x ULN (=< 5 x ULN for patients with liver involvement) (obtained =< 14 days prior to registration)
  • Prothrombin time (PT)/International Normalized Ratio (INR)/activated partial thromboplastin time (aPTT) =< 1.5 x ULN OR if patient is receiving anticoagulant therapy and INR or aPTT is within target range of therapy (obtained =< 14 days prior to registration)
  • Calculated creatinine clearance >= 30 ml/min using the Cockcroft-Gault formula (obtained =< 14 days prior to registration)
  • Female participants: Female participant is eligible to participate if she is not pregnant or breast feeding, and at least one of the following conditions applies:

    • Is not a woman of childbearing potential (WOCBP) OR
    • Due to lenalidomide being a thalidomide analogue with risk for embryofetal toxicity and prescribed under a pregnancy prevention/controlled distribution program, and bortezomib having the potential to cause fetal harm, WOCBP participants will be eligible if they commit to either:

      • Abstain continuously from heterosexual sexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR
      • To use birth control as follows:

        • Two methods of reliable birth control (one method that is highly effective and one additional effective (barrier) method), beginning 4 weeks prior to initiating treatment with lenalidomide, during therapy, during dose interruptions and continuing for 4 weeks following discontinuation of lenalidomide treatment. Thereafter, WOCBP participants must use one method of reliable birth control that is highly effective for a further 4 months following discontinuation of belantamab mafodotin or a further 2 months after discontinuation of daratumumab. WOCBP must also agree not to donate eggs (ova, oocytes) for the purpose of reproduction during treatment, during dose interruptions and for 28-days following the last dose of lenalidomide, or 4 months following discontinuation of belantamab mafodotin treatment, whichever is longer.

          • Note: 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 an early undetected pregnancy
  • Male participants: Male participants are eligible to participate if they agree to the following from the time of first dose of study treatment until 28-days after the last dose of lenalidomide, or 6 months after the last dose of belantamab mafodotin, whichever is longer, 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 as when having sexual intercourse with a woman of childbearing potential (including pregnant females)
  • Ability to understand the study procedures and provide written informed consent
  • Negative hepatitis B test (defined by a negative test for hepatitis B surface antigen [HBsAg], or antibodies to hepatitis B surface and/or core antigens [antiHBs or antiHBc])

    • Note: Participants with serologic findings suggestive of HBV vaccination (antiHBs positivity as the only serologic marker) AND a known history of prior hepatitis B virus (HBV) vaccination do not need to be tested for HBV deoxyribonucleic acid (DNA) by polymerase chain reaction (PCR). Those who are PCR positive will be excluded from the study
  • Participant agrees not to use contact lenses while participating in the study
  • Willingness to provide mandatory bone marrow and blood specimens for research
  • Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)
  • 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

Exclusion Criteria:

  • Monoclonal gammopathy of undetermined significance or smoldering multiple myeloma
  • Major surgery =< 28 days prior to registration
  • Plasmapheresis =< 14 days prior to registration
  • Diagnosed or treated for another malignancy =< 2 years prior to registration or previously diagnosed with another malignancy and have any evidence of residual disease

    • Note: Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection
    • Note: If there is a history of prior malignancy, they must not be receiving other specific treatment (hormone therapy, chemotherapy, or immunotherapy) for their cancer
  • Receiving any other concurrent chemotherapy, systemic steroids, any ancillary therapy considered investigational for treatment of multiple myeloma, or receiving radiotherapy =< 14 days or five half-lives, whichever is shorter, prior to first dose of study treatment. Note: Bisphosphonates are considered to be supportive care rather than therapy and are thus allowed while on protocol treatment
  • Known to be human immunodeficiency virus (HIV) positive
  • Presence of positive hepatitis C antibody test result or positive hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study treatment

    • 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
  • Uncontrolled intercurrent illness including, but not limited to:

    • Ongoing or active infection (defined as infection undergoing treatment)
    • Active mucosal or internal bleeding
    • Social situations that would limit compliance with study requirements.
    • Corneal epithelial disease (except for mild changes in the corneal epithelium)
    • Known gastrointestinal disease (including difficulty swallowing) or gastrointestinal procedure that could interfere with the oral absorption or tolerance of lenalidomide or dexamethasone
    • Unstable liver or biliary disease defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. Note: Stable non-cirrhotic chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) or hepatobiliary involvement of malignancy is acceptable if otherwise meets entry criteria
    • Active renal condition (infection, requirement for dialysis or any other condition that could affect participant's safety). Note: Participants with isolated proteinuria resulting from MM are eligible, provided they fulfill inclusion criteria
  • Evidence of cardiovascular disease risk, as defined by any of the following:

    • Evidence of current clinically significant uncontrolled arrhythmias, including clinically significant electrocardiogram (ECG) abnormalities such as 2nd degree (Mobitz 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 =< 90 days prior to registration
    • Class III or IV heart failure as defined by the New York Heart Association functional classification system
    • Uncontrolled hypertension
  • History of myocardial infarction, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
  • Known allergies, hypersensitivity, or intolerance to corticosteroids, monoclonal antibodies or human proteins, or their excipients (refer to respective package inserts or Investigator's Brochure) or known sensitivity to belantamab mafodotin or drugs chemically related to belantamab mafodotin, or any of the components of the study treatment

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): NCT04892264


Locations
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United States, Minnesota
Mayo Clinic in Rochester Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Referral Office    855-776-0015    mayocliniccancerstudies@mayo.edu   
Principal Investigator: Shaji K. Kumar, M.D.         
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Shaji K Kumar Mayo Clinic in Rochester
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Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT04892264    
Other Study ID Numbers: MC1989
NCI-2021-03479 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MC1989 ( Other Identifier: Mayo Clinic in Rochester )
P30CA015083 ( U.S. NIH Grant/Contract )
First Posted: May 19, 2021    Key Record Dates
Last Update Posted: June 13, 2022
Last Verified: June 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
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
Dexamethasone acetate
Lenalidomide
Daratumumab
Ichthammol
BB 1101
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