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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04181827




Registration number
NCT04181827
Ethics application status
Date submitted
27/11/2019
Date registered
2/12/2019

Titles & IDs
Public title
A Study Comparing JNJ-68284528, a CAR-T Therapy Directed Against B-cell Maturation Antigen (BCMA), Versus Pomalidomide, Bortezomib and Dexamethasone (PVd) or Daratumumab, Pomalidomide and Dexamethasone (DPd) in Participants With Relapsed and Lenalidomide-Refractory Multiple Myeloma
Scientific title
A Phase 3 Randomized Study Comparing JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against BCMA, Versus Pomalidomide, Bortezomib and Dexamethasone (PVd) or Daratumumab, Pomalidomide and Dexamethasone (DPd) in Subjects With Relapsed and Lenalidomide-Refractory Multiple Myeloma
Secondary ID [1] 0 0
68284528MMY3002
Secondary ID [2] 0 0
CR108695
Universal Trial Number (UTN)
Trial acronym
CARTITUDE-4
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Cilta-cel
Treatment: Drugs - Pomalidomide
Treatment: Drugs - Bortezomib
Treatment: Drugs - Dexamethasone
Treatment: Drugs - Daratumumab

Experimental: Arm A: PVd or DPd (Standard Therapy) - Participants will receive either PVd or DPd as a standard therapy. In PVd treatment, participants will receive oral pomalidomide 4 mg on Days 1 to 14 in each cycle; bortezomib 1.3 mg/meter square (m\^2) SC on Days 1, 4, 8 and 11 (Cycles 1 to 8) and on Days 1 and 8 (Cycle 9 onwards) and oral dexamethasone 20 mg on Days 1, 2, 4, 5, 8, 9, 11 and 12 (Cycles 1 to 8) and Days 1, 2, 8 and 9 (Cycle 9 onwards). Each cycle will consist of 21 days. In DPd treatment, participants will receive daratumumab SC 1800 mg weekly on Days 1, 8, 15, and 22 (Cycles 1 and 2), every 2 weeks on Days 1 and 15 (Cycles 3 to 6) and every 4 weeks on Day 1 (Cycle 7 onwards); oral pomalidomide 4 mg on Days 1 to 21 (Cycle 1 onwards); dexamethasone 40 mg oral or IV weekly on Days 1, 8, 15, and 22 (Cycle 1 onwards). Each cycle will consist of 28 days. Participants will continue to receive PVd or DPd until confirmed PD, death, intolerable toxicity, withdrawal of consent, or end of the study, whichever occurs earlier.

Experimental: Arm B: (Ciltacabtagene Autoleucel [Cilta-cel]) - Participants will receive at least one cycle of bridging therapy (PVd or DPd) and additional cycles of bridging therapy may be considered based on participant's clinical status and timing of availability of cilta-cel along with conditioning regimen (cyclophosphamide 300 milligram \[mg\]/m\^2 intravenous \[IV\] and fludarabine 30 mg/m\^2 IV daily, for 3 days), and cilta-cel infusion 0.75 \* 10\^6 chimeric antigen receptor (CAR)-positive viable T cells/ kilogram (kg).


Treatment: Drugs: Cilta-cel
Cilta-cel infusion will be administered at a target dose of 0.75 \* 10\^6 CAR-positive viable T cells/kilogram (kg).

Treatment: Drugs: Pomalidomide
Pomalidomide 4 mg will be administered orally.

Treatment: Drugs: Bortezomib
Bortezomib 1.3 milligram per meter square (mg/m\^2) will be administered subcutaneously (SC).

Treatment: Drugs: Dexamethasone
Dexamethasone 20 mg/day (10mg/day for participants \>75 years of age) (on bortezomib treatment days and the days following bortezomib treatment) will be administered orally in PVd treatment; and orally or intravenous (IV) at 40 mg weekly (20mg weekly for participants \>75 years of age) in DPd treatment.

Treatment: Drugs: Daratumumab
Daratumumab 1800 mg will be administered SC.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival (PFS)
Assessment method [1] 0 0
PFS is defined as the time from the date of randomization to the date of first documented disease progression as defined in the IMWG criteria, or death due to any cause, whichever occurs first.
Timepoint [1] 0 0
Until end of the study (up to 6 years)
Secondary outcome [1] 0 0
Complete Response (CR) or Stringent Complete Response (sCR) Rate
Assessment method [1] 0 0
CR or sCR rate is defined as percentage of participants who achieve a CR or sCR response according to the International Myeloma Working Group (IMWG) criteria.
Timepoint [1] 0 0
Until end of the study (up to 6 years)
Secondary outcome [2] 0 0
Overall Minimal Residual Disease (MRD) Negative Rate
Assessment method [2] 0 0
Overall MRD negativity is defined as the percentage of participants who achieve MRD negativity at any time after the date of randomization before initiation of subsequent therapy.
Timepoint [2] 0 0
Until end of the study (up to 6 years)
Secondary outcome [3] 0 0
MRD Negativity Rate in Participants with CR or sCR at 12 Months +/-3 Months
Assessment method [3] 0 0
MRD negativity rate in participants with CR or sCR at 12 months +/-3 months is defined as the percentage of participants who achieve MRD-negative status and are in CR or sCR within time window.
Timepoint [3] 0 0
Until end of the study (up to 6 years)
Secondary outcome [4] 0 0
Sustained MRD Negative Rate
Assessment method [4] 0 0
Sustained MRD negativity rate is defined as the percentage of participants who achieve MRD negativity, confirmed minimum 1 year apart and without any examination showing MRD positive status in between.
Timepoint [4] 0 0
Until end of the study (up to 6 years)
Secondary outcome [5] 0 0
Overall Survival (OS)
Assessment method [5] 0 0
OS is measured from the date of randomization to the date of the participant's death. If the participant is alive or the vital status is unknown, then the participant's data will be censored at the date the participant was last known to be alive.
Timepoint [5] 0 0
Until end of the study (up to 6 years)
Secondary outcome [6] 0 0
Overall response rate (ORR)
Assessment method [6] 0 0
ORR is defined as the percentage of participants who achieve a partial response (PR) or better according to the IMWG criteria.
Timepoint [6] 0 0
Until end of the study (up to 6 years)
Secondary outcome [7] 0 0
Time to Worsening of Symptoms
Assessment method [7] 0 0
Time to worsening of symptoms is measured as the interval from the date of randomization to the start date of worsening in the Multiple Myeloma Symptom and Impact Questionnaire (MySIm-Q) total symptom score. The MySIm-Q is a disease-specific PRO assessment complementary to the EORTC-QLQ-C30. It includes 17 items resulting in a symptom subscale and an impact subscale. The recall period is the "past 7 days" and responses are reported on a 5 point verbal rating scale.
Timepoint [7] 0 0
Until end of the study (up to 6 years)
Secondary outcome [8] 0 0
Progression Free Survival on next-line therapy (PFS2)
Assessment method [8] 0 0
PFS2 is defined as the time interval between the date of randomization and date of event, which is defined as progressive disease as assessed by investigator that starts after the next line of subsequent therapy, or death from any cause, whichever occurs first.
Timepoint [8] 0 0
Until end of the study (up to 6 years)
Secondary outcome [9] 0 0
Incidence and Severity of Adverse Events (AEs)
Assessment method [9] 0 0
Incidence and severity of AEs will be reported.
Timepoint [9] 0 0
Until end of the study (up to 6 years)
Secondary outcome [10] 0 0
Systemic Cytokine Concentrations
Assessment method [10] 0 0
Serum or plasma proteomic profiling of cytokines (such as interleukin \[IL\] 6, IL-15, and IL 10) concentrations will be measured for biomarker assessment.
Timepoint [10] 0 0
Until end of the study (up to 6 years)
Secondary outcome [11] 0 0
Levels of CAR-T Cell Activation Markers
Assessment method [11] 0 0
CAR-T cell activation markers including, but not limited to, CD4+, CD8+, CD25+, central memory, effector memory cells will be reported. An evaluation of cell populations may be performed by flow cytometry or cytometry by time of flight (CyTOF) or both and correlated with response.
Timepoint [11] 0 0
Until end of the study (up to 6 years)
Secondary outcome [12] 0 0
Levels of JNJ-68284528 T Cell Expansion (proliferation), and Persistence
Assessment method [12] 0 0
Levels of JNJ-68284528 T cell expansion (proliferation), and persistence via monitoring CAR-T positive cell counts and CAR transgene level will be reported.
Timepoint [12] 0 0
Until end of the study (up to 6 years)
Secondary outcome [13] 0 0
Number of Participants with Anti-JNJ-68284528 Antibodies
Assessment method [13] 0 0
Number of participants exhibiting anti-drug antibodies for JNJ-68284528 will be reported.
Timepoint [13] 0 0
Until end of the study (up to 6 years)
Secondary outcome [14] 0 0
Change from Baseline in Health-Related Quality of Life (HRQoL) as Assessed by European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC-QLQ-C30) Scale Score
Assessment method [14] 0 0
The EORTC QLQ-C30 includes 30 items in 5 functional scales, 1 global health status scale, 3 symptom scales, and 6 single symptom items. The responses are reported using a verbal rating scale. The item and scale scores are transformed to a 0 to 100 scale. A higher score represents greater HRQoL, better functioning, and more (worse) symptoms.
Timepoint [14] 0 0
Until end of the study (up to 6 years)
Secondary outcome [15] 0 0
Change from Baseline in Health-Related Quality of Life as Assessed by MySIm-Q Scale Sore
Assessment method [15] 0 0
The MySIm-Q is a disease-specific PRO assessment complementary to the EORTC-QLQ-C30. It includes 17 items resulting in a symptom subscale and an impact subscale. The recall period is the "past 7 days" and responses are reported on a 5 point verbal rating scale.
Timepoint [15] 0 0
Until end of the study (up to 6 years)
Secondary outcome [16] 0 0
Change from Baseline in Health-Related Quality of Life as Assessed by European Quality of Life - 5 Dimensions-5 Levels (EQ-5D-5L) Scale Score
Assessment method [16] 0 0
The EQ-5D-5L is a generic measure of health status. The EQ-5D-5L is a 5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression plus a visual analog scale rating "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).
Timepoint [16] 0 0
Until end of the study (up to 6 years)
Secondary outcome [17] 0 0
Change from Baseline in Health-Related Quality of Life as Assessed by Patient Global Impression of Symptom Severity (PGIS) Scale Score
Assessment method [17] 0 0
The PGIS is a single item to assess the participant's perception in the severity of their overall health status using a 5-point verbal rating scale. Score ranges from 1 (None) to 5 (Very Severe).
Timepoint [17] 0 0
Until end of the study (up to 6 years)
Secondary outcome [18] 0 0
Frequency in Health-Related Quality of Life as Assessed by The Patient-reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Item
Assessment method [18] 0 0
Frequency distributions of the PRO-CTCAE is an item library of common adverse events experienced by people with cancer that are appropriate for self-reporting. Each symptom selected for inclusion can be rated by up to 3 attributes characterizing the presence/frequency, severity, and/or interference of the adverse event. A 5-point verbal rating scale is used for participants to select their experience based on the last 7 days.
Timepoint [18] 0 0
Until end of the study (up to 6 years)

Eligibility
Key inclusion criteria
* Measurable disease at screening as defined by any of the following: (a) Serum monoclonal paraprotein (M-protein) level greater than or equal to (>=) 0.5 gram per deciliter (g/dL) or urine M-protein level >=200 milligram (mg)/24 hours; or (b) Light chain multiple myeloma without measurable M-protein in the serum or the urine: Serum free light chain >=10 mg/dL and abnormal serum free light chain ratio
* Have received 1 to 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD)
* Have documented evidence of PD by International Myeloma Working Group (IMWG) criteria based on investigator's determination on or within 6 months of their last regimen
* Be refractory to lenalidomide per IMWG consensus guidelines (failure to achieve minimal response or progression on or within 60 days of completing lenalidomide therapy). Progression on or within 60 days of the last dose of lenalidomide given as maintenance will meet this criterion. For participants with more than 1 prior line of therapy, there is no requirement to be lenalidomide refractory to the most recent line of prior therapy. However, participants must be refractory to lenalidomide in at least one prior line
* Have clinical laboratory values meeting the following criteria during the Screening Phase (re testing is allowed but the below criteria must be met in the latest test prior to randomization):

1. Hemoglobin >=8 gram per deciliter (g/dL) (without prior RBC transfusion within 7 days before the laboratory test; recombinant human erythropoietin use is permitted);
2. Absolute neutrophil count (ANC) >=1 * 10^9 per liter (L) (without recombinant human granulocyte colony-stimulating factor [G-CSF] within 7 days and without pegylated G-CSF within 14 days of the laboratory test);
3. Platelet count >=75 * 10^9/L (without prior platelet transfusion within 7 days before the laboratory test) in participants in whom less than (<) 50 percent (%) of bone marrow nucleated cells are plasma cells; platelet count >=50 * 10^9/L (without prior platelet transfusion within 7 days before the laboratory test) in participants in whom >=50% of bone marrow nucleated cells are plasma cells;
4. Lymphocyte count >=0.3 * 10^9/L;
5. Aspartate aminotransferase (AST) less than or equal to (<=)3 * upper limit of normal (ULN);
6. Alanine aminotransferase (ALT) <=3 * ULN;
7. Total bilirubin <=2.0 * ULN; except in participants with congenital bilirubinemia, such as Gilbert syndrome (in which case direct bilirubin <=1.5 * ULN is required);
8. Estimated glomerular filtration rate >=40 milliliter per minute (mL/min) per 1.73 meter square (m^2) (to be calculated using the Modification of Diet in Renal Disease [MDRD] formula)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Prior treatment with chimeric antigen receptor T-cell (CAR-T) therapy directed at any target
* Any previous therapy that is targeted to B-cell maturation antigen (BCMA)
* Ongoing toxicity from previous anticancer therapy that has not resolved to baseline levels or to Grade 1 or less; except for alopecia
* Participants with Grade 1 peripheral neuropathy with pain or Grade 2 or higher peripheral neuropathy will not be permitted to receive pomalidomide, bortezomib, and dexamethasone (PVd) as standard therapy or bridging therapy; however, participants may receive daratumumab, pomalidomide, and dexamethasone (DPd) as standard therapy or bridging therapy
* Received a cumulative dose of corticosteroids equivalent to >=70 mg of prednisone within the 7 days prior to randomization
* Monoclonal antibody treatment within 21 days
* Cytotoxic therapy within 14 days
* Proteasome inhibitor therapy within 14 days
* Immunomodulatory drug (IMiD) therapy within 7 days

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/06/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/06/2027
Actual
Sample size
Target
Accrual to date
Final
419
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [3] 0 0
Royal Brisbane and Womens Hospital - Herston
Recruitment hospital [4] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [5] 0 0
Alfred Health - Melbourne
Recruitment hospital [6] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
2050 - Camperdown
Recruitment postcode(s) [3] 0 0
4029 - Herston
Recruitment postcode(s) [4] 0 0
3000 - Melbourne
Recruitment postcode(s) [5] 0 0
3004 - Melbourne
Recruitment postcode(s) [6] 0 0
6150 - Murdoch
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Iowa
Country [8] 0 0
United States of America
State/province [8] 0 0
Kansas
Country [9] 0 0
United States of America
State/province [9] 0 0
Maryland
Country [10] 0 0
United States of America
State/province [10] 0 0
Minnesota
Country [11] 0 0
United States of America
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Missouri
Country [12] 0 0
United States of America
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New Jersey
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New York
Country [14] 0 0
United States of America
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North Carolina
Country [15] 0 0
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Ohio
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Utah
Country [17] 0 0
United States of America
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Wisconsin
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Belgium
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Antwerp
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Belgium
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Gent
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Belgium
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Leuven
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Belgium
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Liege
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Denmark
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Copenhagen
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France
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LILLE Cedex
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France
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Montpellier
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France
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Nantes
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Paris cedex 10
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France
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Pierre Benite cedex
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France
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Poitiers
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France
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Toulouse cedex 9
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Germany
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Dresden
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Germany
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Hamburg
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Germany
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Koeln
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Germany
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Leipzig
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Germany
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Tubingen
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Wuerzburg
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Greece
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Athens
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Israel
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Jerusalem
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Israel
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Ramat Gan
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Israel
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Tel Aviv
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Italy
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Bologna
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Milano
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Italy
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Roma
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Italy
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Turin
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Japan
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Fukuoka
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Japan
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Kanazawa
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Kyoto
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Nagoya
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Okayama
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Sapporo
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Sendai
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Japan
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Shibuya
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Korea, Republic of
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Seoul
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Netherlands
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Amsterdam
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Groningen
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Rotterdam
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Utrecht
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Poland
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Gdansk
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Gliwice
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Poznan
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Warszawa
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Spain
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Badalona
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Barcelona
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Madrid
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Pamplona
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Salamanca
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Sevilla
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Sweden
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Lund
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Stockholm
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Sweden
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Uppsala
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United Kingdom
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Birmingham
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Bristol
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Cardiff
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London
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Manchester
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United Kingdom
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Newcastle Upon Tyne

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Janssen Research & Development, LLC
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 0 0
Janssen Research & Development, LLC Clinical Trial
Address 0 0
Janssen Research & Development, LLC
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04181827