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Multiple MyelomaPhase 1/2NCT04822337

Study of Carfilzomib, Lenalidomide, Dexamethasone and Belantamab Mafodotin in Multiple Myeloma

A Phase 1/2 study testing Carfilzomib, Lenalidomide, Dexamethasone, Belantamab Mafodotin in people with Multiple Myeloma, run by Wake Forest University Health Sciences at 2 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

This research study is being done to learn if the study drug belantamab mafodotin, in combination with other standard medications, can improve multiple myeloma. This study will also help determine what effects, good and/or bad, this combination of study drugs have on subjects and their cancer, and to evaluate the… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma
What is being tested?
Carfilzomib, Lenalidomide, Dexamethasone, Belantamab Mafodotin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
70 participants
Where
2 sitesUnited States
Study dates
19 May 2021to Nov 2032
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Written informed consent and HIPAA authorization for release of personal health information signed by the subject or his/her legally authorized representative. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
  • Age greater than or equal to 18 years at the time of consent. Because no dosing or adverse event data are currently available on the use of belantamab mafodotin as a single agent or in combination with KRd in subjects less than 18 years of age, children are excluded from this study.
  • ECOG Performance Status of less than or equal to 2
  • Demonstrate adequate organ function
  • Adequate cardiac function as defined by a greater than 40% left ventricular ejection fraction (LVEF) by ECHO, cardiac MRI or MUGA
  • Note for subjects in phase II: if a cycle of pre-study induction therapy containing a PI or anthracycline was administered, assessment of the LVEF must be repeated.
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  • For those with symptomatic pulmonary disease with Grade 2 or higher symptoms (e.g. COPD, asthma) or other signs / symptoms of pulmonary disease, adequate pulmonary function as defined by a FEV1 greater than or equal to 50% of predicted and DLCO/VA greater than or equal to 50% of predicted
  • Females of childbearing potential (FCBP) must have two negative serum pregnancy tests during screening: the first within 10-14 days prior to first dose of study treatment and the second within 24 hours prior to first dose of study treatment. NOTE: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), are amenorrhoeic for less than 2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation; or are postmenopausal (at least 12 consecutive months with no menses without an alternative medical cause).
  • FCBP must be willing to use 2 effective contraceptive methods (at least one that is highly effective) or abstinence starting from the time of informed consent, while on belantamab mafodotin and lenalidomide. If either drug is discontinued, 2 effective forms of contraception should be continued until at least 4 weeks after the last dose of lenalidomide, and 1 form of effective contraception should be continued until 4 months post last dose of belantamab mafodotin. FCBP should use effective contraception or abstinence from consent until 30 days after last treatment with carfilzomib, and males with a partner of childbearing potential must use effective contraception or abstinence for at least 90 days post last dose of carfilzomib.
  • Male subjects must agree to the following from the first dose of study treatment until 6 months after the last dose of belantamab mafodotin, to allow for clearance of 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 c. Must agree to use effective contraception/barrier as detailed below: Agree to use a male condom, even if they have undergone a successful vasectomy, and female partner of reproductive potential to use an additional highly effective contraceptive method with a failure rate of less than 1% per year
  • FCBP must agree not to donate eggs (ova, oocytes) for the purpose of reproduction during the intervention period and for at least 4 months after the last dose of study intervention belantamab mafodotin, at least 30 days after the last dose of carfilzomib, and at least 4 weeks after the last dose of lenalidomide.
  • As determined by the enrolling physician, ability of the subject to understand and adhere with study procedures for the entire length of the study
  • Ability to swallow oral medications
  • Willing to refrain from using contact lenses while participating in this study
  • INCLUSION CRITERIA - Phase I treatment for Relapsed or Relapsed/Refractory MM:
  • Subjects with Relapsed or Relapsed/Refractory MM who have had at least 1 line of prior therapy.
  • Refractory is defined as less than 25% reduction in M-protein or progression of disease during treatment or within 60 days after cessation of treatment b. A line of therapy is defined as one or more cycles of a planned treatment program. This may consist of one or more planned cycles of single-agent therapy or combination therapy, as well as a sequence of treatments administered in a planned manner. A new line of therapy starts when a planned course of therapy is modified to include other treatment agents (alone or in combination) as a result of disease progression, relapse, or toxicity. A new line of therapy also starts when a planned period of observation off therapy is interrupted by a need for additional treatment for the disease.
  • Subjects must have measurable disease, as defined by at least one of the following:
  • Serum monoclonal protein level greater than or equal to 0.5 g/dL b. 24-hour urinary M-protein greater than or equal to 200 mg c. Involved free light chain level greater than or equal to 10 mg/dL, along with an abnormal free light chain ratio (defined as less than 0.26 or greater than 1.65).
  • Subject must have not progressed on full dose lenalidomide previously (25 mg on days 1-21 of a 28-day cycle or its dosing equivalent based on renal function at the time of progression)
  • Prior to enrollment:
  • There should be a washout period of ≥14 days from any prior chemotherapy AND
  • The subject must have adequate recovery from toxicity of prior chemotherapy as defined by the following:
  • Hematologic lab results within parameters noted in Table 3.2.1 ii. Non-hematologic toxicity resolved to grade 1 or baseline with the following exceptions:
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  • Subjects who have started a course of antibiotic therapy for infection and symptoms have improved to baseline or grade 1, but remain on antibiotic therapy are eligible
  • Subjects with ≤grade 2 fatigue are eligible
  • Subjects with ≤grade 2 hyperglycemia are eligible, even if pharmacologic treatment was required
  • Subjects with ≤grade 2 electrolyte abnormalities are eligible, even if pharmacologic treatment was required
  • Subjects with ≤grade 2 nausea, constipation or diarrhea are eligible, even if pharmacologic treatment was required
  • Subjects with less than grade 2 peripheral neuropathy
  • INCLUSION CRITERIA - Phase II treatment for high-risk newly diagnosed MM:
  • Active, newly diagnosed multiple myeloma with CRAB features or a myeloma-defining event per the IMWG 2014 criteria. Note: It is acceptable to include subjects who have had one cycle of emergent treatment for multiple myeloma.
  • High-risk disease at diagnosis, as defined by at least one of the following:
  • Monoallelic del(1p) along with +1q, or biallelic del(1p) ii. One of those translocations [t(4;14), t(14;16) or t(14;20)]- co-occurring with a +1q and/or del(1p) iii. del(17p)* and/or TP53 mutation iv. High β2M (>5.5 mg/L) with normal creatinine (Note: Both must be performed no more than +/- 7 days apart.) v. Primary plasma cell leukemia: peripheral blood plasma cell percentage >5% as assessed by pathology review of the peripheral smear vi. Presence of extramedullary disease
  • Measurable disease by 1 or more of the following:
  • Serum monoclonal protein level greater than or equal to 0.5 g/dL b. 24-hour urinary M-protein greater than or equal to 200 mg c. Involved free light chain level greater than or equal to 10 mg/dL (100 mg/L), along with an abnormal free light chain ratio (defined as less than 0.26 or greater than 1.65).
  • Note: for subjects who have received a prior cycle of non-protocol therapy, measurable disease will be based on the serum and urine monoclonal protein and serum free light chain levels prior to the cycle of non-protocol therapy
  • No more than one prior cycle of non-protocol therapy will be allowed, recognizing that high-risk multiple myeloma subjects frequently require immediate therapy at initial diagnosis even before risk assessment is complete. For those subjects who receive a cycle of non-protocol induction therapy:
  • There should be a washout period of ≥14 days from the last dose of pre-study therapy AND
  • The subject must have adequate recovery from toxicity of pre-study therapy as defined by the following:
  • Hematologic lab results within parameters ii. Non-hematologic toxicity resolved to grade 1 or baseline with the following exceptions:
  • <!-- -->
  • Subjects who have started a course of antibiotic therapy for infection and symptoms have improved to baseline or grade 1, but remain on antibiotic therapy are eligible
  • Subjects with less than or equal to grade 2 fatigue are eligible
  • Subjects with less than or equal to grade 2 hyperglycemia are eligible, even if pharmacologic treatment was required
  • Subjects with less than or equal to grade 2 electrolyte abnormalities are eligible, even if pharmacologic treatment was required
  • Subjects with less than or equal to grade 2 nausea, constipation or diarrhea are eligible, even if pharmacologic treatment was required
  • Subjects with less than grade 2 peripheral neuropathy

Who cannot join

  • Active infection requiring systemic therapy. NOTE: at the discretion of the treating investigator, subjects who have started antibiotic therapy for subjects who had symptoms present, symptoms must have improved to baseline or grade 1 in severity may start treatment prior to completion of their course of antibiotic therapy.
  • Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study.)
  • Subjects cannot have other prior or concomitant malignancies except for:
  • Curatively treated non-melanoma skin cancer b. Other cancer for which the subject has been medically stable for at least 2 years and/or, in the opinion of the Site Principal Investigators, will not affect the evaluation of the effects of clinical trial treatments on the currently targeted malignancy
  • Active central nervous system (CNS) involvement
  • Concomitant AL amyloidosis or POEMS syndrome
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  • Treatment with any investigational drug within 14 days or five half-lives, whichever is shorter, prior to first dose of study treatment.
  • Medical, psychiatric, or other condition/disorder (including lab abnormalities) which, in the opinion of the treating physician, would make this protocol treatment unreasonably hazardous for the subject, or could interfere with obtaining informed consent or compliance to the study procedures
  • Significant cardiac disease, including any of the following:
  • Greater than or equal to Class 3 New York Heart Association (NYHA) congestive heart failure (see Appendix B) b. ECG evidence of acute ischemia c. Unstable angina d. Myocardial infarction, Coronary angioplasty, stenting, or bypass grafting within three months prior to day 1 of treatment e. Clinically significant uncontrolled and/or untreated arrhythmias or conduction block, including clinically significant ECG abnormalities such as 2nd degree Mobitz Type ll or 3rd degree atrioventricular (AV)block. However, PACs, PVCs, rate controlled atrial fibrillation, sinus arrhythmia, asymptomatic sinus bradycardia or sinus tachycardia and 1st degree heart block are not considered clinically significant.
  • Greater than or equal to Grade 2 QTcF prolongation (i.e. >480 msec)
  • Chronic uncontrolled hypertension, defined as a systolic blood pressure of greater than or equal 160 mmHg or a diastolic blood pressure of greater than or equal 90 mmHg based on at least two readings on two or more separate occasions, ideally over 1-4 weeks. Isolated or situational blood pressure elevations may be acceptable at the treating investigator's discretion.
  • Grade greater than or equal to 2 peripheral neuropathy
  • Psychiatric illness/social situation that would limit compliance with study requirements as determined by the investigator
  • Known immediate or delayed hypersensitivity or allergic reaction to any components of, or related to, protocol therapy (e.g. during exposure to carfilzomib, lenalidomide or dexamethasone as part of a pre-study cycle of therapy).
  • History of erythema multiforme to lenalidomide or other IMID
  • Discontinuation of prior carfilzomib, lenalidomide or dexamethasone due to treatment toxicity
  • Major surgery within 4 weeks prior to day 1 of treatment
  • Radiation within 14 days prior to day 1 of treatment. Note: palliative XRT to less than 5% of the total marrow volume as assessed by the treating investigator is allowed within 14 days prior to day 1 of treatment
  • Current corneal epithelial disease except mild changes in corneal epithelium
  • Positive hepatitis C antibody test result (this test preferable) or positive hepatitis C RNA test result at screening or within 3 months prior to first dose of study treatment
  • NOTE: Subjects with positive Hepatitis C antibody due to prior eradicated disease can be enrolled if a confirmatory negative Hepatitis C RNA test is obtained b. Positive hepatitis C antibody test result or positive hepatitis C RNA test result at screening or within 3 months before first dose of study treatment unless the participant can meet the following criteria: i. RNA test negative ii. Successful antiviral treatment (usually 8 weeks duration) is required, followed by a negative HCV RNA test after a washout period of at least 4 weeks.
  • NOTE: Hepatitis RNA testing is optional and participants with a negative hepatitis C antibody test are not required to also undergo hepatitis C RNA testing
  • A known diagnosis of HIV
  • Is seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Subjects with resolved infection (i.e. subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Subjects who are PCR positive will be excluded. Subjects with Hepatitis B surface antibodies and previous Hepatitis B vaccination will be eligible.
  • Has 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 non-cirrhotic chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) or hepatobiliary involvement of malignancy is acceptable if otherwise meets entry criteria
  • Participant must not have presence of active renal condition (infection, requirement for dialysis or any other condition that could affect participant's safety). Participants with isolated proteinuria resulting from MM are eligible, provided they fulfill inclusion criteria
  • Participant must not have had plasmapheresis within 7 days prior to first dose of study treatment
  • Any evidence of active mucosal or internal bleeding
  • Participant must not be simultaneously enrolled in any therapeutic clinical trial
  • Administration of live or live-attenuated vaccines within 30 days prior to the first dose of study treatment a. Exception: Monkeypox vaccine may be given if there are at least 3 days between the vaccine and initiation of study treatment.
  • 28. Prior treatment with a monoclonal antibody within 30 days of receiving the first dose of study drug.
  • 29. Transplant ineligible per institutional guidelines (Phase II)

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Kelly Bumgarner, RN contact

704-403-2520

kelly.bumgarner@atriumhealth.org

Shebli Atrash, MD, MS contact

704-774-9322

Shebli.Atrash@atriumhealth.org

United States2 sites, 2 recruiting

  • Levine Cancer Institute

    Charlotte, North Carolina, 28204

    Shelby Clark, RN, 980-442-2341, Shelby.Clark@advocatehealth.org

    Recruiting

  • Atrium Health Wake Forest Baptist Comprehensive Cancer Center

    Winston-Salem, North Carolina, 27157

    John McKay, DO, (336) 713-5440, John.Mckay@wfusm.edu

    John McKay, DO

    Recruiting

Other trials in United States

About this study

Official title: A Phase I/II Study of Carfilzomib, Lenalidomide, Dexamethasone and the Anti-B-Cell Maturation Antigen (BCMA) Antibody Drug Conjugate Belantamab Mafodotin in Multiple Myeloma

This research study is being done to learn if the study drug belantamab mafodotin, in combination with other standard medications, can improve multiple myeloma. This study will also help determine what effects, good and/or bad, this combination of study drugs have on subjects and their cancer, and to evaluate the overall response to this study treatment combination.

Read the detailed description

This is a phase I dose escalation and expansion study in RMM and RRMM followed by a single arm phase II expansion in high risk, NDMM. The phase I portion of the protocol will utilize a standard 3+3 dose escalation design to determine the maximum tolerated dose (MTD) and RP2D of the KRd-belantamab mafodotin combination. The phase II portion of the trial is a two-stage design that will assess the efficacy and safety of the combination in newly diagnosed, high-risk MM patients.

Being tested
Carfilzomib, Lenalidomide, Dexamethasone, Belantamab Mafodotin
Keywords
Plasma Cell Neoplasms, BCMA
Medical subject headings
Multiple Myeloma, Neoplasms, Plasma Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Carfilzomib, Lenalidomide, Dexamethasone, Belantamab MafodotinDrug

    Phase I - Chemotherapy multiple agents systemic Phase II - Maximum Tolerated Dose from Phase I

Study groups in NCT04822337
Study groupRoleWhat they receive
Phase IExperimentalCarfilzomib, Lenalidomide, Dexamethasone, Belantamab Mafodotin
Receives: Drug: Carfilzomib, Lenalidomide, Dexamethasone, Belantamab Mafodotin
Phase IIExperimentalCarfilzomib, Lenalidomide, Dexamethasone, Belantamab Mafodotin
Receives: Drug: Carfilzomib, Lenalidomide, Dexamethasone, Belantamab Mafodotin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Establish Maximum Tolerated Dose (MTD)

    DLTs will be determined for each subject enrolled in Phase I as a binary variable indicating whether the subject experienced a DLT during Cycle 1 of belantamab mafodotin-containing protocol directed induction therapy.

    Measured: time to complete Cycle 1 (28 days)

  2. Evaluate Complete Response (CR)

    CR will be determined for each subject as a binary variable indicating whether the achieved a best overall response to induction therapy of CR or better.

    Measured: up to 5 years

Secondary outcomes (11)

  1. Complete Response (CR)

    CR will be determined for each subject as a binary variable indicating whether the achieved a best overall response to induction therapy of CR or better

    Measured: Up to 5 years

  2. Best Response

    The best overall response will be determined as an ordered categorial variable indicating the subject's best response at any point along the treatment continuum.

    Measured: Up to 5 years

  3. Very Good Partial Response (VGPR)

    will be determined for each subject as a binary variable indicating whether the achieved a best overall response to induction therapy of VGPR or better.

    Measured: up to 5 year

  4. Overall Response

    The best overall response will be determined as an ordered categorial variable indicating the subject's best response at any point along the treatment continuum

    Measured: up to 5 years post treatment discontinuation

  5. MRD Negative

    . Minimal residual disease (MRD) (via NGF 10-5 and 10-6) will be determined for each subject after suspected CR for Phase I subjects and at the following timepoints for Phase II subjects: after induction therapy, after ASCT, and after 12 cycles of maintenance therapy (post Cycle 18visit) and every 12 months post Cycle 18 sample.

    Measured: Up to 5 years

  6. Time to First Response (TTFR)

    TTFR will be calculated for all subjects achieving an sCR, CR, VGPR, or PR. This will be defined as the time from initiation of belantamab mafodotin-containing protocol directed induction therapy to the time of first disease assessment indicating either sCR, CR, VGPR or PR

    Measured: up to 30 days post treatment discontinuation

  7. Time to Best Response (TTBR)

    Time to best response will be calculated for all subjects achieving an sCR, CR, VGPR or PR. This will be defined as the time from initiation of belantamab mafodotin-containing protocol directed induction therapy to the time of best disease assessment indicating either sCR, CR, VGPR or PR.

    Measured: up to 30 days post treatment discontinuation

  8. Time to Progression (TTP)

    TTP is defined as the duration of time from enrollment to the study (treatment start date) to first occurrence of progressive disease

    Measured: Up to 5 years

  9. Duration of Response (DoR)

    DoR will be calculated for each subject achieving a PR or better and will be calculated from the time of the first assessment that identified response until disease progression or death.

    Measured: Up to 5 years post treatment response

  10. Overall Survival (OS)

    OS is defined as the duration from enrollment to the study (treatment start date) to the date of death from any cause.

    Measured: Up to 8 years

  11. Progression Free Survival (PFS)

    PFS is defined as the duration of time from enrollment to the study (treatment start date) to first occurrence of either progressive disease or death (from any cause), whichever comes first.

    Measured: Up to 8 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Mar 2021
  2. Study start19 May 2021
  3. Primary completionApr 2029 (estimated)
  4. Study completionNov 2032 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
70 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04822337
Sponsor's protocol ID
IRB00081609
Other IDs
Pro00050160, LCI-HEM-NDMYE-KRDB-001
Status last verified
Oct 2026
First submitted
26 Mar 2021
Last updated
26 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Atrash S, Symanowski J, Robinson M, Flynn C, Norek S, Cox R, Plott M, Bumgarner K, Rhinehardt D, Begic X, Ndiaye A, Robinson J, Friend R, Paul B, Varga C, Ferreri C, Pineda-Roman M, Foureau D, Bhutani M, Voorhees P. Belantamab mafodotin, carfilzomib, lenalidomide, and dexamethasone for relapsed or refractory multiple myeloma. Blood Adv. 2026 May 12;10(9):2925-2936. doi: 10.1182/bloodadvances.2025019050.

    PubMed 41719502

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Carfilzomib, Lenalidomide, Dexamethasone, Belantamab Mafodotin in people with Multiple Myeloma, run by Wake Forest University Health Sciences at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 52 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 26 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Kelly Bumgarner, RN (704-403-2520, kelly.bumgarner@atriumhealth.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Establish Maximum Tolerated Dose (MTD) (time frame: time to complete Cycle 1 (28 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04822337, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2026.

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