Descartes-11 Consolidation Treatment in Patients With High-Risk Multiple Myeloma Who Have Residual Disease After Induction Therapy
Phase: PHASE2
Conditions: Multiple Myeloma
Sponsor: Cartesian Therapeutics

 
 
 
 
 
 
CLINICAL STUDY PROTOCOL 
 
 
TITLE: Descartes-11 Consolidation Treatment in Patients With High-Risk Multiple 
Myeloma Who Have Residual Disease After Induction Therapy 
 
 
Protocol number: 
DC11B 
IND number: 
 
 
Investigators: 
Multi-center 
 
Sponsor: 
Cartesian Therapeutics, Inc. 
 
Address: 
 
 
Phone: 
 
 
Website: 
www.cartesiantherapeutics.com 
 
e-mail: 
 
 
Study Product: 
Descartes-11 
Original Protocol Date: 
03-MAR-2020 
Current Version: 
1.0 

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INVESTIGATOR’S AGREEMENT 
I have received and read the investigator’s brochure for Descartes-11. I have read protocol and 
agree to conduct the study as outlined and in conformance with Good Clinical Practices (GCPs) 
and applicable regulatory requirements. I agree to maintain the confidentiality of all information 
received or developed in connection with this protocol. 
 
 
 
 
Printed Name of Investigator 
 
 
 
 
 
Signature of Investigator 
 
 
 
 
Date 

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TABLE OF CONTENTS 
SPONSOR SIGNATURE PAGE .......................................................................................... 2 
INVESTIGATOR’S AGREEMENT ..................................................................................... 3 
ABBREVIATIONS AND DICTIONARY OF TERMS......................................................... 7 
     INTRODUCTION ........................................................................................................... 9  
1.1 
Study Objectives .................................................................................................. 9 
1.1.1 
Primary Objective .................................................................................... 9 
1.1.2 
Secondary Objectives ............................................................................... 9 
1.1.3 
Exploratory Objectives ............................................................................. 9 
1.2 
Background and Rationale ................................................................................. 10 
1.2.1 
Epidemiology of High-Risk Multiple Myeloma ...................................... 10 
1.2.2 
Definition of High-Risk Multiple Myeloma ............................................ 10 
1.2.3 
Treatment of High-Risk Multiple Myeloma ............................................ 10 
1.2.4 
MRD as Clinical Outcome in Myeloma Patients ..................................... 11 
1.2.5 
CAR-T Therapy in Multiple Myeloma ................................................... 11 
1.2.6 
Rationale for Current Protocol ................................................................ 13 
1.2.7 
Rationale for use of MRD testing as Primary Endpoint ........................... 14 
1.3 
Study Drug ........................................................................................................ 14 
1.3.1 
Description ............................................................................................. 14 
1.3.2 
Route of Administration and Dosing Regimen........................................ 14 
1.3.3 
Nonclinical and Clinical Data ................................................................. 14 
ELIGIBILITY AND ENROLLMENT ........................................................................... 15 
2.1 
Eligibility Criteria .............................................................................................. 15 
2.1.1 
Inclusion Criteria.................................................................................... 15 
2.1.2 
Exclusion Criteria .................................................................................. 16 
2.2 
Screening, Evaluation and Enrollment ............................................................... 17 
2.2.1 
Recruitment of Patients .......................................................................... 17 
2.2.2 
Screening Evaluation.............................................................................. 17 
2.2.3 
Enrollment ............................................................................................. 17 
2.2.4 
Early Withdrawal of Subjects ................................................................. 17 
2.2.5 
Data Collection and Follow-Up of Early Withdrawals ............................ 17 
     STUDY DESIGN.......................................................................................................... 18  
3.1 
Study Schema .................................................................................................... 18 
3.2 
Study Implementation ........................................................................................ 19 
3.2.1 
Overall Treatment Design ...................................................................... 19 
3.2.2 
Delay of Cell Infusion ............................................................................ 19 

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3.3 
Drug Administration .......................................................................................... 20 
3.3.1 
Preparation and Administration of Study Drug ....................................... 20 
3.3.2 
Return or Destruction of Study Drug ...................................................... 20 
3.3.3 
Post-Infusion Observation ...................................................................... 21 
3.3.4 
Management of Toxicities ...................................................................... 21 
3.3.5 
Concomitant Medications ....................................................................... 22 
3.4 
Anti-Myeloma Treatment Following Descartes-11 ............................................. 23 
     PROTOCOL EVALUATION AND BIOSPECIMEN COLLECTION ............................. 24  
4.1 
Study Procedures ............................................................................................... 24 
4.1.1 
Baseline Evaluation (Day -60 to Day 0).................................................. 24 
4.1.2 
Descartes-11 Infusion (Days 1,4, 8, 11, 15, 18) ...................................... 25 
4.1.3 
Safety and Response Assessment Visit (Day 28 + 3 days) ...................... 25 
4.1.4 
Follow-up Months 1, 3, 6, 9, 12, 18, 24, 36 (+ 2 weeks) ......................... 26 
4.2 
Study Calendar .................................................................................................. 27 
4.3 
Biospecimen Collection for Exploratory Studies ................................................ 29 
4.3.1 
Explanation of Research Blood Assays ................................................... 29 
4.3.2 
Future Studies ........................................................................................ 29 
4.3.3 
Research Blood Sample and Remaining Study Drug Destruction Upon 
Protocol Completion .............................................................................. 30 
4.4 
Treatment Response Assessment........................................................................ 30 
4.5 
Criteria for Removal from Protocol Therapy and Off-Study Criteria .................. 32 
4.5.1 
Criteria for Removal from Descartes-11 Therapy ................................... 32 
4.5.2 
Criteria for Off-Study ............................................................................. 32 
     SAFETY, ADVERSE EVENTS, PROTOCOL DEVIATION AND STOPPING 
RULES ......................................................................................................................... 33 
5.1 
Definitions ......................................................................................................... 33 
5.1.1 
Adverse Events (AE) .............................................................................. 33 
5.1.2 
Suspected Adverse Reaction ................................................................... 33 
5.1.3 
Serious Unexpected Adverse Reaction (SUSAR) ................................... 33 
5.1.4 
Serious Adverse Event (SAE) ................................................................. 34 
5.1.5 
Protocol Deviation ................................................................................. 34 
5.2 
Recording of Adverse Events ............................................................................. 34 
5.2.1 
Adverse Event Recording Period ............................................................ 34 
5.2.2 
Hospitalization, Prolonged Hospitalization or Surgery ............................ 34 
5.2.3 
Pregnancies ............................................................................................ 35 
5.2.4 
Recording of Adverse Events ................................................................. 35 
5.2.5 
SAE and SUSAR Reporting ................................................................... 36 

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5.3 
Medical Monitor ................................................................................................ 38 
5.4 
Recording of Protocol Deviations ...................................................................... 38 
5.5 
Stopping Rules and Study Termination .............................................................. 38 
     STATISTICAL CONSIDERATIONS ........................................................................... 40  
     ETHICAL CONSIDERATIONS ................................................................................... 41  
7.1 
General Issues.................................................................................................... 41 
7.2 
Rationale for Subject Selection .......................................................................... 41 
7.3 
Evaluation of Benefits and Risks ....................................................................... 41 
7.4 
Recordkeeping ................................................................................................... 42 
7.4.1 
Source Data ............................................................................................ 42 
7.4.2 
Case Report Forms ................................................................................. 42 
7.4.3 
Confidentiality ....................................................................................... 42 
7.4.4 
Records Retention .................................................................................. 42 
     PHARMACEUTICAL INFORMATION ...................................................................... 43  
     REFERENCES ............................................................................................................. 44  
 
List of In-Text Tables 
Table 1. 
IMWG Response Criteria ................................................................................ 30 
Table 2. 
Relapse from sCR or MRD-negative Criteria .................................................. 31 
 
 
List of In-Text Figures 
Figure 1. 
Study Schema ................................................................................................. 18 
 
 
List of Appendices 
Appendix A 
Management Guidelines for CAR T-cell-related Toxicities ............................. 49 
Appendix B 
Cell Collection Protocol for the Manufacturing of Descartes Products ............. 51 

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ABBREVIATIONS AND DICTIONARY OF TERMS 
AE 
Adverse Event 
ALL 
Acute Lymphoblastic Leukemia 
ALT 
Alanine aminotransferase 
ASCT 
Autologous stem cell transplant 
ASH 
American Society of Hematology 
AST 
Aspartyl aminotransferase 
AUC 
Area Under the (time-concentration) Curve 
BCMA 
B-Cell Maturation Antigen 
BSC 
CA 
Biological Safety Cabinet 
Cytogenetic Abnormality 
CAR 
Chimeric Antigen Receptor 
CBC 
Complete blood count 
CDR 
Complementarity-Determining Regions 
CLL 
Chronic Lymphocytic Leukemia 
CMC 
Chemistry, Manufacturing, and Controls 
CNS 
Central Nervous System 
CR 
Complete Response 
CrCl 
Creatinine Clearance 
CRS 
Cytokine Release Syndrome 
CSF 
Cerebrospinal fluid 
CT 
Computed Tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
DMF 
Drug Master File 
DNA 
Deoxyribonucleic acid 
ECG 
Electrocardiogram 
FHCRC 
iFISH 
Fred Hutchinson Cancer Research Center 
Interphase Fluorescence In-Situ Hybridization 
FLC 
Free light chain 
GLP 
Good Laboratory Practice 
GM-CSF 
Granulocyte-Macrophage colony-stimulating factor 
GMP 
Good Manufacturing Practice 
GVHD 
Graft-versus-host disease 
HAMA 
Human anti-mouse antibody 
HAS 
Human Serum Albumin 
HBV 
Hepatitis B virus 
HCV 
Hepatitis C virus 
HIV 
Human immunodeficiency virus 
HPLC 
High Performance Liquid Chromatography 
HR 
Hazard Ratio 
IFN-γ 
Interferon-gamma 
IL 
Interleukin 
IMID 
Immunomodulatory drug 

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IMWG 
International Myeloma Working Group 
IND 
Investigational New Drug (application) 
IV 
Intravenous(ly) 
MFC 
Multi-parameter flow cytometry 
MHC 
Major histocompatibility complex 
MM 
Multiple Myeloma 
MOI 
Multiplicity of infection 
MRD 
Minimal Residual Disease 
MTD 
Maximal Tolerated Dose 
NCI 
National Cancer Institute 
NDMM 
Newly Diagnosed Multiple Myeloma 
NGS 
Next Generation Sequencing 
NOAEL 
No Observed Adverse Effect Level 
NSAID 
Non-steroidal anti-inflammatory drug 
MRD 
Minimal Residual Disease 
MRSD 
Maximum Recommended Starting Dose 
MSSD 
Maximum Safe Starting Dose 
NDA 
New Drug Application 
ODD 
Orphan Drug Designation (application) 
OS 
Overall Survival 
PFS 
Progression-Free Survival 
PI 
Proteasome inhibitor 
PK 
Pharmacokinetic 
PR 
Partial Response 
PRBC 
Packed Red Blood Cells 
PRES 
Posterior Reversible Encephalopathy Syndrome 
SAE 
Serious Adverse Event 
sCR 
Stringent Complete Response 
SEM 
Standard Error of the Mean 
SIFE 
Serum immunofixation electrophoresis 
SM 
Starting Materials 
SPEP 
Serum protein electrophoresis 
SPD 
Sum of the Products of the Maximal Perpendicular Diameters 
TK 
Toxicokinetic(s) 
TLS 
Tumor Lysis Syndrome 
TNF α 
Tumor-necrosis factor alpha 
UIFE 
Urine immunofixation electrophoresis 
UPEP 
Urine protein electrophoresis 
VGPR 
Very Good Partial Response 

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1.2 Background and Rationale 
1.2.1 
Epidemiology of High-Risk Multiple Myeloma 
In 2018, there were over 30,000 new cases of multiple myeloma (MM) and over 10,000 deaths 
from this disease.1 MM is the second most common hematological malignancy in adults after 
lymphoma, with a median survival diagnosis of about 10 years.2 A subgroup of myeloma patients 
carry features that confer poor risk and median survival is usually less than 4 years3. Historically, 
these poor-prognosis patients have been identified using clinical biomarkers such as 
β2-microglobulin and albumin. Based on these two markers, patients were classified into 3 risk- 
category groups in the International Staging System for Myeloma (ISS). With the advent of 
analytical methods that can diagnose chromosomal translocations, such as Fluorescence In Situ 
Hybridization (FISH), genomic changes were found to be independent risk factors for prognosis 
of multiple myeloma regardless of treatment. Based on the International Myeloma Working Group 
(IMWG) consensus, high-risk chromosomal instabilities include translocations of the IgH locus 
on chromosome 14 with an oncogene such as FGFR3/MMSET on chromosome 4 (t(4;14)) or c- 
MAF on chromosome 16 (t(14;16)) or MAFB on chromosome 20 (t(14;20)).3 These translocations 
are observed in 15%, 4% and 1% of the newly diagnosed multiple myeloma (NDMM) patients, 
respectively.4,5 Beside translocations, deletion of p53 on chromosome 17p, non-hyperdiploid 
karyotype, deletion 13 by karyotype, and gain 1q/loss of 1p (seen in 7%, 50% 44%, 30% of newly 
diagnosed multiple myeloma patients, respectively) are also associated with poor survival. 4,5 Each 
of these genomic aberrations has independently similar impact on the outcome of multiple 
myeloma patients while their combination further reduces overall survival. For example, the triple 
combination of an adverse IgH translocation, gain(1q), and del(17p) was associated with a median 
overall survival (OS) of 9.1 months.6 Chromosomal aberrations showing improved outcomes were 
also identified, such as trisomies 3 and 5.7,8 When both favorable and unfavorable cytogenetics 
coincide in the same patient, the unfavorable findings tend to dominate the clinical picture8,9. 
1.2.2 
Definition of High-Risk Multiple Myeloma 
High risk disease is defined by IMWG consensus.3 IMWG defines high-risk disease as either R-
ISS Stage III or by one or more high-risk cytogenetic abnormalities (CAs). 3 R-ISS Stage III is 
defined as serum β-microglobulin ≥5.5 mg/L and either high risk CA by iFISH or high LDH.10 
High–risk CAs are 1) t(4;14), t(14;16), t(14;20), del(17/17p), non-hyperdiploid karyotype, 
gain(1q), del 13, gain 1q, or a high-risk signature on gene expression profile (GEP). 
 
1.2.3 
Treatment of High-Risk Multiple Myeloma 
Bortezomib partly overcomes the adverse effect of t(4;14) and possibly del(17p) on CR, PFS, and 
OS.11-15 A meta-analysis of 4 randomized trials showed that the odds of post-transplantation deep 
response rate (VGPR or better) were similar in high-risk cytogenetics (del(17p) and t(4;14)) and 
standard risk cytogenetics when bortezomib was used in the induction treatment.13 An integrated 
analysis of phase III trials demonstrates PFS benefit in patients with t(4;14) but lacking del(17p) 
and in del(17p) lacking t(4;14) but not in patients carrying both abnormalities.16 Thus, a 
bortezomib-based induction regimen, and if patient is eligible followed by high dose 
therapy/ASCT, ideally shortly after completion of 6-8 cycles of initial therapy, is the recommended 
treatment in NDMM with high-risk features.3 Typically after 3-4 cycles of multi-drug induction 
regimen, treatment is paused briefly for stem cell collection and then treatment is completed to 6- 

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8 cycles. However, this regimen results in MRD-negativity in only 20% of patients17 and CR only 
in 30-35%18,19 of patients, and the median Event-Free Survival remains at 14-24 months depending 
on the cytogenetic abnormality.11 In patients who do not receive ASCT in frontline therapy but 
receive PI/lenalidomide based regimen, achieve 15% CR20 and with addition of cyclophosphamide 
35% CR with only half of them being MRD negative.21 Thus, there is clear need for intensifying 
the upfront treatment in this patient population. Despite this need, there is no consensus on the 
appropriate subsequent therapy for these patients. Prevailing approaches include proteasome 
inhibitor/immunomodulatory drug combination maintenance, a second autotransplant, or even an 
allotransplant.3,16,22 A meta-analysis of 4 European trials showed that double ASCT combined with 
a bortezomib-based treatment regimen partially abrogates poor PFS in patients carrying both 
t(4;14) and del(17p)16, and limited data with RVD maintenance given up to 3 years post-transplant 
suggests some benefit in a group with del p53, del 1p; (t(4;14) or t(14;16)) with an sCR rate of 
50%.23 Although long-term PFS can be achieved with allogeneic HSCT, the benefits of graft- 
versus-myeloma effect are limited by high treatment-related mortality (TRM), approaching 40% 
for myeloablative transplantations.24 Clinical trial enrollment for high-risk NDMM is therefore 
recommended by multiple expert groups.18,22 
1.2.4 
MRD as Clinical Outcome in Myeloma Patients 
MRD testing in NDMM patients following first-line therapy was originally developed using multi- 
color flow cytometry,25 which has been widely used in several trials for multiple myeloma.26,27 
Due to their superior sensitivity, genomic testing like Next Generation Sequencing (NGS) or IgH 
became the preferred method of MRD testing. Specifically, flow cytometry-based MRD assays 
can detect 1 myeloma cell in 100,000 bone marrow cells; current genetic MRD assays can detect 
1 myeloma cell in 1,000,000 bone marrow cells.28 This is important because the depth of MRD 
correlates with PFS.29,30,31,32 Data are limited in patients with high-risk myeloma but also show 
that MRD is an independent risk factor in high-risk myeloma.33 Therefore multiple expert reviews 
propose that MRD testing should and will become a primary regulatory efficacy endpoint.3,22,34 
1.2.5 
CAR-T Therapy in Multiple Myeloma 
B-cell maturation antigen (BCMA), also known as tumor necrosis factor receptor superfamily 
member 17 (TNFRSF17) or CD269, is consistently and selectively expressed on normal plasma 
and myeloma cells.35 For this reason, it is a preferred target antigen for CAR immunotherapy of 
MM. Upon engagement by its ligands, i.e., TNFSF13 (APRIL: a proliferation-inducing ligand; 
CD256) and TNFSF13B (BAFF: B cell-activating factor; also known as BLYS or CD257), BCMA 
supports survival of plasma cells.36 
A CAR construct against BCMA was originally developed at the National Cancer Institute (NCI) 
and was introduced into CD3+ cells using a viral transduction system that inserts the gene 
permanently into the genome of the T-cell. At the maximum tolerated dose (MTD) of 9x106 
cells/kg, 63% of the patients achieved very good partial response (VGPR) or better.37 Given the 
promising efficacy of the virally transduced anti-BCMA CAR T-cells, several other groups created 
permanently modified anti-BCMA CAR T-cells now in clinical testing. Bluebird Bio’s anti- 
BCMA-CAR T-cell construct has completed its phase II trial in relapsed refractory patients who 
progressed after at least 2 lines of therapy demonstrated an impressive 85% overall response rate 
(ORR) with 45% of the patients having CR or better response.38,39 Another product originally 
developed in China was recently evaluated in relapsed refractory patients during a Phase I multi- 

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center trial in USA and showed 100% ORR with 61% of the patients achieving CR or better.40 
Similar highly promising result are reported for several other anti-BCMA CAR-T cell products 
developed by different groups confirming the high potency of anti-BCMA CAR T-cells in killing 
myeloma cells. More importantly, this potency is seen across all risk groups, including patients 
with adverse cytogenetics suggesting that CAR T-cell mediated killing is independent of resistance 
mechanisms generated by high-risk chromosomal aberrations. 
 
The potency of virally transduced CAR therapies comes with significant risks. All clinical trials 
of virally transduced CAR T-cells have recorded serious instances of cytokine release syndrome 
(CRS) and neurological toxicity. In the recent American Society of Blood and Marrow Transplant 
(ASBMT) consensus meeting, CRS was defined as “a supraphysiologic response following any 
immune therapy that results in the activation or engagement of endogenous or infused T cells 
and/or other immune effector cells. Symptoms can be progressive, must include fever at the onset, 
and may include hypotension, capillary leak (hypoxia) and end organ dysfunction.”41 CRS is a 
prototypical systemic inflammatory response syndrome that occurs hours to days after CAR T-cell 
infusion. Signs and symptoms include fever, myalgia, malaise, and, in more severe cases, a 
capillary leak syndrome associated with hypoxia, hypotension, and occasionally renal dysfunction 
and coagulopathy. Peak CAR T-cells as a result of in vivo proliferation has been strongly 
associated with the severity of CRS in many CAR  T-cell  studies.42,43  The  proliferation  of 
CAR T-cells upon engagement with target antigen drives them to secrete cytokines that initiates a 
cascade of systemic inflammatory events. Among all cytokines elevated during CRS, IL-6 plays a 
central role as neutralization of this cytokine quickly and effectively reverses clinical deterioration 
in most cases. 
 
The first presenting symptom of CRS is usually fever associated with mild constitutional 
symptoms.42,44-46 In a number of patients, the initial mild symptoms progress over the course of 
hours to days and turn into a systemic inflammatory syndrome characterized by sinus tachycardia, 
hypotension and hypoxia. In severe cases, patients may require mechanical ventilation and 
vasopressors. CRS can start as early as the day of CAR T-cell infusion and in most cases it occurs 
within the first 14 days following the infusion. Severe cases appear to occur closer to the time of 
infusion and the severity of CRS was reported to correlate with peak CAR T-cell levels as 
mentioned above as well as disease burden42,43 and addition of preconditioning 
chemotherapy.43,44,46,47 
Neurotoxicity associated with CAR T-cell treatment, now named “Immune effector cell-associated 
neurotoxicity syndrome” (ICANS) in the ASBMT consensus panel document, is described as “a 
disorder characterized by a pathologic process involving the central nervous system following any 
immune therapy that results in the activation or engagement of endogenous or infused T cells 
and/or other immune effector cells. Reported neurologic toxicities include headaches, confusion, 
alterations in wakefulness, hallucinations, dysphasia, ataxia, apraxia, facial nerve palsy, tremor, 
dysmetria, and seizures43-45,48-53. Neurotoxicity has been reported in several anti-CD19 CAR T-cell 
trials and severe cerebral edema lead to death in a small number of patients54,55. However, it has 
occurred less frequently in anti-BCMA CAR T-cell trials37,39. Factors that underlie CRS like peak 
CAR T-cell levels44,46,54,56 or cytokine levels43,48,52,57 are also associated with neurotoxicity. 
Several grading systems have been developed for CAR T-cell-related CRS and neurotoxicity and 
this protocol uses grading developed based on ASBMT consensus criteria.41 

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Eligibility and Enrollment 
2.1 Eligibility Criteria 
2.1.1 
Inclusion Criteria 
The following inclusion criteria will be applied at Screening, unless another evaluation time point 
is specified: 
 
1. High-risk multiple myeloma patients (defined below) who complete pre-transplant induction 
treatment anti-myeloma drug combination (minimum 2 drugs). 
2. Following completion of the pre-transplant induction regimen, patients must have residual 
disease measured by at least one of the following markers: 
a. Serum M-protein detectable by immunofixation 
b. Urine M-protein detectable by immunofixation 
c. Abnormal FLC ratio 
d. A biopsy-proven plasmacytoma or residual disease on imaging of a spot that was known 
to have plasmacytoma 
e. Evidence of clonal cells in immunohistochemistry defined as Kappa/Lambda <4:1 or >1:2 
after counting > 100 plasma cells 
f. Evidence of MRD detected by DNA-based or flow cytometry approaches 
3. Patients must have high-risk multiple myeloma based on IMWG consensus as defined by R-
ISS Stage III10 or high-risk CA3. 
a. R-ISS Stage III is defined as having serum β-microglobulin ≥5.5 mg/L and either 
a high risk CA by iFISH or high LDH. 
b. High–risk CAs are defined as having 1) t(4;14), t(14;16), t(14;20), or del(17/17p) 
in at least 20% of the cells; 2) any non-hyperdiploid karyotype, 3) gain(1q); 4) del 
13; 5) gain 1q; or 6) a high-risk signature on gene expression profile (GEP). 
4. There should be at least 7 days between the last dose of anti-myeloma drug and first Descartes- 
11 infusion. 
5. Toxicities from prior therapies must have resolved to Grade 2 or less according to the CTCAE 
5.0 criteria, or to the subject’s pre-therapy baseline at the time of first cell infusion. 
6. Patients must have signed written, informed consent. 
7. Patients must be 18 years of age or older at the time of enrollment. 
8. Patients must have clinical performance status of ECOG 0-2. 
9. Patients must be seronegative for HIV. 
10. Patients must be seronegative for hepatitis B (HBV) antigen; or, if the patient is positive for 
the hepatitis B antigen test, he or she must be negative for HBV DNA and must agree to use 
Hepatitis B prophylaxis as per institution guideline and/or principal investigator discretion. 

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11. Patients must be seronegative for hepatitis C (HCV) antibody; or, if the hepatitis C antibody 
test is positive, the patient must be tested for the presence of viremia by RT-PCR and must be 
HCV RNA negative. 
12. Patients must have adequate vital organ function as defined by the following criteria: 
• 
Bone marrow function defined by absolute neutrophil count (ANC) >1000 cells/mm3 and 
platelet count >50,000 cells/mm3 
• 
Serum ALT and AST less or equal to 3 times the upper limit of the institutional normal; 
• 
Total bilirubin ≤ 2.0 mg/dL, except in patients with Gilbert’s Syndrome, who must have a 
total bilirubin less than 3.0 mg/dL; 
• 
Normal cardiac ejection fraction (≥ 45% by echocardiography) and no evidence of 
hemodynamically significant pericardial effusion as determined by an echocardiogram 
within 6 months of the start of the leukapheresis; AND 
• 
Creatinine Clearance (CrCl) ≥ 30 mL/min or 30 mL/min/1.73 m2. 
2.1.2 
Exclusion Criteria 
The following exclusion criteria will be applied at the time of Screening, unless another evaluation 
timepoint is specified: 
 
1. Patients who are pregnant or lactating. 
2. Patients who have any active and uncontrolled infection. No blood cultures are necessary 
unless clinically indicated. 
3. Use of any of the following: 
a. Monoclonal antibody based anti-myeloma treatment prior to Descartes-11 infusion 
b. Experimental anti-myeloma agents prior to Descartes-11 infusion (off-label use of 
other FDA-approved anti-myeloma medications is allowed) 
4. Ongoing treatment with the following immunosuppressants: calcineurin inhibitors 
(i.e. tacrolimus), mTOR inhibitors (i.e. sirolimus) 
5. Patients who have active central nervous system disease. 
6. Patients with second malignancies in addition to MM are not eligible if the second malignancy 
has required treatment within the past 3 years or is not in complete remission. There are three 
exceptions to this criterion are successfully treated 1) non-metastatic basal cell 2) squamous 
cell skin carcinoma, or 3) prostate cancer that has not required anticancer therapy. 
7. Active cardiac arrhythmias, active obstructive or restrictive pulmonary disease. If there is a 
history of cardiac or pulmonary morbidities, the principal investigator will judge whether these 
conditions are active or in stable condition. 
8. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency 
Disease). 
9. History of severe immediate hypersensitivity reaction to any of the agents used in this study. 

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10. Subjects who have had a venous thromboembolic event (e.g., pulmonary embolism or deep 
vein thrombosis) requiring anticoagulation and who meet any of the following criteria: 
• Deep venous thrombosis occurred within the past 3 months OR pulmonary embolism 
occurred within the past 6 months 
• If on anticoagulation, based on PI discretion, anticoagulation cannot be withheld and 
postponed during leukapheresis 
• Have had at least Grade 2 hemorrhage in the last 30 days 
• Are experiencing continued  symptoms  from  their  venous  thromboembolic  event  
(e.g. continued dyspnea or oxygen requirement) 
 
2.2 Screening, Evaluation and Enrollment 
2.2.1 
Recruitment of Patients 
Subjects will be identified through the clinical practices of the investigator or sub-investigators 
and through referrals from outside hospitals and physicians. Patients diagnosed with high-risk 
multiple myeloma can be referred any time after they complete induction therapy. Patient should 
be enrolled and treated with Descartes-11 prior to ASCT if they are transplant eligible. If the 
patient does not have cells available at the time of screening (See Section 3.3.1.1 for details), they 
can be referred to Sponsor’s Cell Collection Protocol (See Appendix B). 
 
2.2.2 
Screening Evaluation 
Please refer to Section 4.1.1 for Screening visit evaluations. 
 
2.2.3 
Enrollment 
To enroll a subject on this study, the following documents are required: 
• Copy of signed/dated consent and HIPAA Authorization 
• Source documentation to confirm enrollment/eligibility 
2.2.4 
Early Withdrawal of Subjects 
Patients who do not complete at least one Descartes-11 infusion will be considered to have 
prematurely discontinued the study. The reasons for premature discontinuation must be recorded 
on the case report form. Final study evaluations will be completed at the time of discontinuation. 
Provided that all protocol requirements are satisfied for the trial to continue safely, patients who 
withdraw early from the study will not be counted toward study recruitment limits. 
 
2.2.5 
Data Collection and Follow-Up of Early Withdrawals 
Patients who withdraw early from the study and who have provided consent for follow-up data 
collection will be eligible for continued data collection for up to one year. Withdrawn patients who 
are followed at other institutions or practices, because of preference or geographical concerns, will 
confer follow-up via notes from their local physician and/or phone interviews. Toxicity and other 
clinical assessments will be obtained from the treating physician and recorded into appropriate 
case report form (CRF). In the event a subject fails to complete the follow-up requirements, all 
attempts to contact the subject including: 1) at least three telephone contacts (on different days and 
at different times of the day), and 2) a certified letter will be documented. 

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3.3.5.3 
Granulocyte Colony-Stimulating Factor 
If the absolute neutrophil count becomes less than 1000/microliter and there is suspicion of or 
documented bacterial infection, then based on the investigator’s discretion, growth factor support 
can be given. Growth factors should be discontinued once the ANC is above 1000/microliter. 
 
3.3.5.4 
Corticosteroids 
Patients should not take systemic corticosteroids (including prednisone, dexamethasone or any 
other corticosteroid) that exceeds a dose equivalent to 40 mg/day or more of prednisone for any 
purpose without approval of the Principle Investigator. In addition, corticosteroids should be 
withheld for 12 hours before and 24 hour after the Descartes-11 infusion. 
 
3.4 
Anti-Myeloma Treatment Following Descartes-11 
After all Descartes-11 infusions and the Day 28 response assessment are completed, further anti- 
myeloma treatment can be administered. The treatment choice is left to investigator’s discretion. 
If the patient is eligible for transplant, high dose chemotherapy and ASCT can be given. Patient 
will be followed-up during this period to evaluate the clinical outcomes for secondary objectives. 

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Protocol Evaluation and Biospecimen Collection 
4.1 Study Procedures 
4.1.1 
Baseline Evaluation (Day -60 to Day 0) 
1. 
Obtain informed consent 
2. 
Review of records for documentation of high-risk multiple myeloma (R-ISS Stage III or at 
least one of the following: t(4;14), t(14;16), t(14;20), del(17/17p), del13, gain 1q, non- 
hyperdiploid karyotype) 
3. 
Complete medical history and physical examination, including, height, weight and vital 
signs (should always include pulse oximetry unless stated otherwise), and ECOG 
performance score. 
4. 
Concomitant medications 
5. 
Complete blood count, differential 
6. 
Chemistry panel (Glucose, Ca, Mg, Phos, Alk Phos, Albumin, Total Protein, Total 
Bilirubin, K, Na, Cl, HCO3, BUN, Uric Acid, Cr, ALT, AST, lactate dehydrogenase) 
7. 
PT/INR, PTT 
8. 
D-Dimer, fibrinogen 
9. 
Urinalysis 
10. CRP, ferritin 
11. β2-microglobulin 
12. Infectious Panel: Hepatitis B Surface Ag (HBsAg), Hepatitis B Core Total Ab, Hepatitis C 
Virus Ab (anti-HBc), HIV-1/HIV-2 Ab 
13. Lymphocyte sub-set counts (CD19, CD3, CD4, CD8, CD56) 
14. Serum protein electrophoresis (SPEP) and serum immunofixation electrophoresis (SIFE) 
15. 24-h urine for urine protein electrophoresis (UPEP) and urine immunofixation 
electrophoresis (UIFE) 
16. Serum free light chain (FLC) assay 
17. Unilateral bone marrow aspirate + biopsy, including bone marrow immunohistochemistry 
and bone marrow flow cytometry 
18. If the prospective subject has known or suspected extramedullary plasmacytomas, previous 
imaging results will be reviewed to confirm the status of the lesions and a repeat imaging 
(i.e., CT scan) can be done if the principal investigator deems it necessary to document the 
size/scope of the lesion. 
19. ECG 
20. ABO typing 
21. Echocardiogram to assess left ventricular function if not performed within the last 6 months 
22. β- HCG for all women of child-bearing potential. Female subjects of reproductive potential 
(women who have reached menarche and who have not been post-menopausal for at least 
24 consecutive months, i.e., who have had menses within the preceding 24 months, or have 
not undergone a sterilization procedure (hysterectomy or bilateral oophorectomy) must 
have a negative serum pregnancy test performed at the time of screening and must agree 
not to participate in a conception process (e.g., active attempt to become pregnant or to 
impregnate sperm donation or in vitro fertilization) until 4 months after receiving 
preconditioning chemotherapy. Additionally, if participating in sexual activity that could 

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lead to pregnancy, the subject must agree to use a reliable method of contraception during 
their participation in the study (e.g., condoms (male or female) with or without a 
spermicidal agent, diaphragm or cervical cap with spermicide, or intrauterine device 
(IUD)). 
23. Research blood (See Laboratory Manual for collection details) 
 
4.1.2 
Descartes-11 Infusion (Days 1,4, 8, 11, 15, 18) 
If not performed in the past 7 days and within one day of the first Descartes-11 infusion at least 
one of the following should be performed if abnormal at screening: 
• Serum protein electrophoresis (SPEP) and serum immunofixation electrophoresis (SIFE); 
• 24-h urine for urine protein electrophoresis (UPEP) and urine immunofixation 
electrophoresis (UIFE); 
• Serum free light chain (FLC) assay 
 
Prior to infusion of cells, the following assessments must be completed: 
1. 
Medical history for adverse events 
2. 
Vital signs including pulse oximetry and physical exam including brief neurological exam 
3. 
Concomitant medications 
4. 
ECOG performance status 
5. 
Urine pregnancy test for all women of child-bearing potential 
6. 
Research Blood (See Laboratory Manual for collection details) 
 
Only on Days 1, 8, 15 the following laboratory assessments will be also be performed prior to 
infusion: 
1. Chemistry panel (Glucose, Ca, Mg, Phos, Albumin, Total Protein, Total Bilirubin, K, Na, Cl, 
HCO3, BUN, Cr, ALT, AST, lactate dehydrogenase) 
2. CRP, ferritin 
3. Urinalysis 
Complete blood count, differential 
 
After infusion of cells, the following assessments must be completed: 
1. Within  5±2  min  of  completing  each  infusion,  Research  blood  should  be  collected.   
See Laboratory Manual for collection details. 
2. Vital signs (See Section 3.3.3 for details) 
 
4.1.3 
Safety and Response Assessment Visit (Day 28 + 3 days) 
During the visit, the following assessment must be completed: 
1. 
Medical history for adverse events 
2. 
Vital signs including pulse oximetry, weight and physical exam including brief 
neurological exam 
3. 
ECOG performance status 
4. 
Concomitant medications 
5. 
Complete blood count, differential 
6. 
Chemistry panel (Glucose, Ca, Mg, Phos, Albumin, Total Protein, Total Bilirubin, K, Na, 
Cl, HCO3, BUN, Cr, ALT, AST, lactate dehydrogenase) 
7. 
Urinalysis 

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8. 
Urine pregnancy test for all women of child-bearing potential 
9. 
CRP, ferritin 
10. Research blood (See Laboratory Manual for collection details) 
11. If present at baseline, serum protein electrophoresis (SPEP), serum immunofixation 
electrophoresis (SIFE) 
12. If present at baseline, 24-h urine for total protein, urine protein electrophoresis (UPEP), urine 
immunofixation electrophoresis (UIFE) 
13. If present at baseline, serum free light chain (FLC) assay 
14. β2- microglobulin 
15. If required for depth-of-response evaluation based on peripheral markers, then unilateral 
bone marrow aspirate + biopsy, including bone marrow immunohistochemistry and bone 
marrow flow cytometry. MRD assessment (with NGS) is performed if patient is in sCR. 
16. Imaging of a previously known plasmacytoma if already imaged at baseline visit 
 
4.1.4 
Follow-up Months 1, 3, 6, 9, 12, 18, 24, 36 (+ 2 weeks) 
1. 
Medical history for adverse events 
2. Current medical conditions and physical examination (including weight, vital signs, pulse 
oximetry) 
3. ECOG performance status 
4. Concomitant medications 
5. Complete blood count, differential 
6. 
Chemistry panel (Glucose, Ca, Mg, Phos, Albumin, Total Protein, Total Bilirubin, K, Na, 
Cl, HCO3, BUN, Cr, ALT, AST, lactate dehydrogenase) 
7. Urinalysis 
8. If present at baseline, serum protein electrophoresis (SPEP), serum immunofixation 
electrophoresis (SIFE) 
9. If present at baseline, 24-h urine for total protein, urine protein electrophoresis (UPEP), urine 
immunofixation electrophoresis (UIFE) 
10. If present at baseline, serum free light chain (FLC) assay 
11. β2- microglobulin 
Additional notes: 
• 
If required for depth-of-response evaluation based on peripheral markers, then unilateral bone 
marrow aspirate + biopsy, including bone marrow immunohistochemistry and bone marrow 
flow cytometry. MRD assessment (with NGS) is performed if patient is in sCR. 
• 
Imaging of a previously known plasmacytoma if already imaged at baseline visit 
• 
Research Blood (See Laboratory Manual for collection details) 

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4.2 Study Calendar 
 
Screening 
Descartes-11 Infusion 
Response 
Assessment 
Follow-Up 
Procedures 
Day -60 to Day 0 
Day 1 
Day 4 
Day 8 
Day 11 
Day 15 
Day 18 
Day 28 
Months 
1,3,6,9,12,18,24,36 
Informed consent 
Eligibility 
Demographics 
X 
Physical exam 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Performance Score 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital Signs, O2 
saturation 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Height 
X 
Weight 
X 
X 
Serious Adverse 
Events 
X 
X 
X 
X 
X 
X 
X 
Adverse events 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant 
Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Descartes-11 
X 
X 
X 
X 
X 
X 
CBC w/ differential 
X 
X 
X 
X 
X 
Chemistrya 
X 
X 
X 
X 
X 
PT/INR, PTT 
X 
CRP, ferritin 
X 
X 
Urinalysis 
X 
X 
X 
X 
X 
β-HCGb 
X 
X 
Urine pregnancy testb 
X 
X 
X 
X 
X 
X 
Lymphocyte subset 
countsc 
X 
Serum FLC ratio 
X 
Xg 
X 
X 

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Screening 
Descartes-11 Infusion 
Response 
Assessment 
Follow-Up 
Procedures 
Day -60 to Day 0 
Day 1 
Day 4 
Day 8 
Day 11 
Day 15 
Day 18 
Day 28 
Months 
1,3,6,9,12,18,24,36 
Serum 
electrophoresis and 
immunofixation 
X 
Xg 
X 
X 
β2-microglobulin 
X 
X 
X 
24-hour urine for 
electrophoresis and 
immunofixation 
X 
Xg 
X 
X 
Bone marrow biopsy 
and aspiration 
X 
Xi 
Xi 
Research Bloodd 
X 
X 
X 
X 
X 
X 
X 
X 
ECG 
X 
Echocardiogramh 
X 
Imaging 
Xf 
Xj 
Xj 
Infectious Disease 
panele 
X 
a Chemistry includes Glucose, Ca, Mg, Phos, ALP, Albumin, Total protein, Total bilirubin, K, Na, Cl, HCO3, BUN, Uric acid, Cr, ALT, AST, LDH 
b Child-bearing women only 
c Lymphocyte subset includes CD19+, CD3+, CD4+, CD8+, CD56+ cells 
d Details of Research Blood collection is explained in Laboratory Manual. 
e Infectious Disease panel includes Hep B surface antigen, Hep B core total antibody. Hep C Virus Ab, HIV-1/HIV-2 
f ONLY if there is known plasmacytoma at baseline. 
g One of these should be done if not performed within the past 7 days 
h If not done in the previous 6 months. 
i Bone marrow aspiration and biopsy tests will be performed ONLY if needed for depth-of-response or relapse evaluation. 
j ONLY if there is known plasmacytoma at baseline and is required for evaluating depth of response based on IMWG criteria (Table 1). 

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4.5 Criteria for Removal from Protocol Therapy and Off-Study 
Criteria 
4.5.1 
Criteria for Removal from Descartes-11 Therapy 
Off-treatment criteria mainly apply to eligibility for potential repeat Descartes-11 treatments. 
Completion of each cycle includes a response assessment visit. Patients will be taken off treatment 
for the following: 
• General or specific changes in the patient's condition render the patient unacceptable for further 
treatment on this study in the judgment of the investigator. 
• Any Descartes-11-related Grade 3 to 5 toxicity occurring within the 14 days immediately after 
infusion of the drug product, with the following exceptions: 
• ≤Grade 3 to 4 Tumor Lysis Syndrome (TLS) lasting <7 days 
• Grade 2 CRS associated with fever, hypotension or hypoxia lasting less than 72 hours 
(i.e., improves to ≤Grade 1 CRS in less than 72 hours) 
• Non-hematologic toxicities: 
o Fever of any grade, including febrile neutropenia 
o ≤Grade 3 diarrhea lasting <72 hours 
o ≤Grade 3 nausea and/or vomiting lasting <72 hours 
o ≤Grade 3 fatigue lasting <7 days 
o ≤Grade 4 transaminase, bilirubin, blood urea nitrogen (BUN), or creatinine 
elevation lasting <7 days 
• Hematologic toxicities: 
o ≤Grade 3 neutropenia of any duration or Grade 4 neutropenia lasting <28 days 
o ≤Grade 3 anemia of any duration or Grade 4 anemia lasting <28 days 
o ≤Grade 3 thrombocytopenia of any duration or Grade 4 thrombocytopenia lasting 
<28 days 
o All cytopenias except neutropenia, anemia, and thrombocytopenia as described 
above 
The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) 
Version 5 will be used to grade toxicities during the trial unless specified above. 
 
4.5.2 
Criteria for Off-Study 
Patients will be taken off study for the following: 
• The patient voluntarily withdraws 
• There is significant patient noncompliance 
• Death 
• Development of progressive or relapsed MM after completing Descartes-11 infusions 
 
Patients must be followed until all adverse events have resolved to grade 2 or less other than 
lymphopenia or alopecia. If an adverse event is not expected to resolve to Grade 2 or less, this will 
be noted in the patient medical record and the patient will be taken off-study. Patients, upon 
obtaining consent, will also be followed for additional clinical outcomes like overall survival. 

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Safety, Adverse Events, Protocol Deviation and Stopping 
Rules 
5.1 Definitions 
5.1.1 
Adverse Events (AE) 
An adverse event (AE) is defined as any reaction, side effect, or untoward event that occurs during 
the clinical trial associated with the use of a test article in humans, whether or not the event is 
considered related to the treatment or clinically significant. For this study, AEs will include events 
reported by the patient, as well as clinically significant abnormal findings on physical examination 
or laboratory evaluation. A new illness, symptom, sign or worsening of a pre-existing condition or 
abnormality is considered an AE. An abnormal laboratory value will be considered an AE if the 
laboratory abnormality is characterized by any of the following: 
• 
Results in discontinuation from the study 
• 
Is associated with clinical signs or symptoms 
• 
Requires treatment or any other therapeutic intervention 
• 
Is associated with death or another serious adverse event, including hospitalization. 
• 
Is judged by the Investigator to be of significant clinical impact 
 
All AEs, including clinically significant abnormal findings on laboratory evaluations, regardless 
of severity, will be followed until satisfactory resolution. 
 
5.1.2 
Suspected Adverse Reaction 
Suspected adverse reaction means any adverse event for which there is a reasonable possibility 
that the test article caused the adverse event. For the purposes of IND safety reporting, “reasonable 
possibility” means there is evidence to suggest a causal relationship between the test article and 
the adverse event. A suspected adverse reaction implies less certainty about causality than adverse 
reaction, which means any adverse event caused by a test article. 
 
5.1.3 
Serious Unexpected Adverse Reaction (SUSAR) 
An adverse event or suspected adverse reaction is considered "unexpected" if it is not listed in the 
investigator brochure or is not listed at the specificity or severity that has been observed; or, if an 
investigator brochure is not required or available, is not consistent with the risk information 
described in the general investigational plan or elsewhere in the current application. "Unexpected" 
also refers to adverse events or suspected adverse reactions that are mentioned in the investigator 
brochure as occurring with a class of the test article or as anticipated from the pharmacological 
properties of the drug but are not specifically mentioned as occurring with the test article under 
investigation. 

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5.1.4 
Serious Adverse Event (SAE) 
An adverse event or suspected adverse reaction is considered serious if in the view of the 
investigator or the sponsor, it results in any of the following: 
• 
Death within 30 days of Descartes-11 infusion 
• 
Grade 4 or 5 CRS, infusion reaction, neurotoxicity 
• 
Inpatient hospitalization or prolongation of existing hospitalization (except for protocol- 
mandated ~24-hour admission for observation due to new-onset fever) 
• 
Persistent or significant incapacity or substantial disruption of the ability to conduct normal 
life functions 
• 
A congenital anomaly/birth defect 
• 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered a SAE experience when, based upon appropriate medical 
judgment, they may jeopardize the patient or subject and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition. 
 
 
5.1.5 
Protocol Deviation 
A one-time, unintentional action or process that departs from the IRB-approved study protocol, 
involving one incident and identified retrospectively, after the event occurred. Any leukapheresis- 
related failure or deviation will be recorded, even if it does not constitute a per-protocol AE. 
 
5.2 Recording of Adverse Events 
5.2.1 
Adverse Event Recording Period 
The study period during which adverse events must be reported is normally defined as the period 
from the initiation of any study procedures to the protocol therapy completion. For this study, 
collection of adverse events will begin with enrollment until the subject is off-study. Serious 
Adverse Event reporting period starts with leukapheresis and ends at 30 days after last Descartes- 
11 infusion. 
 
All unresolved adverse events should be followed by the investigator until the events are resolved, 
the subject is lost to follow-up, or the adverse event is otherwise explained. At the last scheduled 
visit, the investigator should instruct each subject to report any suspected adverse event(s) that 
might reasonably be related to participation in this study. The investigator should notify the 
Sponsor of any death or adverse event occurring at any time after a subject has discontinued or 
terminated study participation if the event may reasonably be related to this study. The Sponsor 
should also be notified if the investigator should become aware of the development of cancer or of 
a congenital anomaly in a subsequently conceived offspring of a subject that has participated in 
this study. 
 
5.2.2 
Hospitalization, Prolonged Hospitalization or Surgery 
Any adverse event that results in hospitalization or prolonged hospitalization should be 
documented and reported as a serious adverse event unless specifically instructed otherwise as 

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below. Any condition responsible for surgery should be documented as an adverse event if the 
condition meets the criteria for an adverse event. Neither the condition, hospitalization, prolonged 
hospitalization, nor surgery are reported as an adverse event in the following circumstances: 
 
• 
Hospitalization or prolonged hospitalization for diagnostic or elective surgical procedures for 
a preexisting condition. Surgery should not be reported as an outcome of an adverse event if 
the purpose of the surgery was elective or diagnostic and the outcome was uneventful. 
• 
Hospitalization or prolonged hospitalization for therapy of the target disease of the study, 
unless there is clinical worsening or an increase in frequency of hospital admissions as judged 
by the clinical investigator. 
• 
Hospitalization for protocol-mandated 24-hour observation following new onset of fever 
following infusion of Descartes-11. 
 
 
5.2.3 
Pregnancies 
To ensure patient safety, each pregnancy in a patient on study treatment must be reported to the 
Sponsor within 24 hours of learning of its occurrence. The pregnancy must be followed up to 
determine outcome, including spontaneous or voluntary termination, details of the birth, and the 
presence or absence of any birth defects, congenital abnormalities, or maternal and/or newborn 
complications. Pregnancy should be recorded on a Clinical Study Pregnancy Form and reported 
by the investigator to the Sponsor. Pregnancy follow-up should be recorded on the same form and 
must include an assessment of the possible relationship to the study treatment of any pregnancy 
outcome. Any SAE experienced during pregnancy must be reported on the SAE Report Form. 
Pregnancy outcomes must be collected for the female partners of any males who took study 
treatment in this study. Consent to report information regarding these pregnancy outcomes should 
be obtained from the mother. 
 
5.2.4 
Recording of Adverse Events 
At each contact with the subject during the adverse  event  recording  period  (defined  in  
Section 5.2.1), the investigator must seek information on adverse events by specific questioning 
and, as appropriate, by examination. Information on all adverse events should be recorded 
immediately in the source document, and in the appropriate adverse event module of the case 
report form (CRF). All clearly related signs, symptoms, and abnormal diagnostic procedures 
results should be recorded in the source document, though should be grouped under one diagnosis. 
To the extent possible, adverse events should be recorded as a diagnosis and symptoms used to 
make the diagnosis recorded within the diagnosis event. Do not list symptoms if a diagnosis can 
be assigned. 
 
Conditions that were already present at the time of informed consent should be recorded in the 
Medical History CRF. Any condition listed in a subject’s medical history for which the severity 
increases at the time of, or post-Descartes-11 infusion, should be captured as an adverse event. 
 
Adverse events (including lab abnormalities that constitute AEs) should be described using a 
diagnosis whenever possible, rather than individual underlying signs and symptoms. When a clear 
diagnosis cannot be identified, each sign or symptom should be reported as a separate Adverse 
Event. The clinical course of each event should be followed until resolution, stabilization, or until 

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it has been determined that the study treatment or participation is not the cause. As detailed as 
possible, each adverse event should be evaluated to determine: 
 
• 
The severity grade (CTCAE Version 5.0 Grade 1-5) 
• 
Its duration (start and end dates) 
• 
Its relationship to the study treatment: Is there a reasonable possibility that the AE is related to 
Descartes-11- No (unrelated) or Yes. If yes- is the event definitely, probably, possibly or 
unlikely related to the investigational treatment (Descartes-11). 
• 
Action taken with respect to study or investigational treatment (none, dose adjusted, 
temporarily interrupted, permanently discontinued, unknown, not applicable) 
• 
Whether medication or therapy taken (i.e., no concomitant medication/non-drug therapy, 
concomitant medication/non-drug therapy) 
• 
Whether it is serious, as defined in Section 5.1. 
 
All adverse events should be treated appropriately. If a concomitant medication or non-drug 
therapy is given, this action should be recorded on the Adverse Event CRF. Adverse events should 
be entered into the eCRF system within 10 working days from the knowledge of the event took 
place. Once an adverse event is detected, it should be followed until its resolution or until it is 
judged to be permanent, and assessment should be made at each visit (or more frequently, if 
necessary) of any changes in severity, the suspected relationship to the study treatment, the 
interventions required to treat it, and the outcome. 
 
Progression of malignancy (including fatal outcomes), documented appropriately in the medical 
records, should not be reported as a serious adverse event. Adverse events that occur concurrently 
with the progression of malignancy but that are not related to disease progression (i.e., deep vein 
thrombosis) will be reported as an adverse event as described above. 
 
5.2.5 
SAE and SUSAR Reporting 
To ensure patient safety, every SAE and SUSAR, regardless of suspected causality, occurring 
during the adverse event reporting period defined in Section 5.2.1 must be reported to the Sponsor 
within 24 hours of learning of its occurrence. Recurrent episodes, complications, or progression of 
the initial SAE must be reported as follow-up information is received. An SAE occurring at a 
different time interval or otherwise considered completely unrelated to a previously reported one 
should be reported separately as a new event. 
 
5.2.5.1 
Study Sponsor Notification by the Investigator 
Any SUSAR and SAE as defined in Section 5.1 must be reported to the Sponsor by email or fax 
within 24 hours of knowledge of the event. To the extent possible, adverse events should be 
recorded as a diagnosis. Do not list symptoms if a diagnosis can be assigned. At the time of the 
initial notification, a serious adverse event (SAE) report form should be filled. Following 
parameters will be asked in the form: 
• 
Subject information 
• 
A description of the event (if there is a diagnosis, it should be included) 
• 
Date of onset 

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• 
Current status 
• 
Whether study treatment was discontinued 
• 
The reason why the event is classified as serious 
• 
Investigator assessment of the association between the event and study treatment 
• 
Concomitant medications when the event happened 
• 
Narrative summary of the event 
 
Follow-up information on this event should be reported when received. The follow-up information 
should describe 1) whether the event has resolved or continues, 2) if and how it was treated, and 
3) whether the patient continued or withdrew from study participation. 
 
5.2.5.2 
IRB Notification by the Investigator 
Following events should be reported to IRB: 
 
• 
Information that indicates a change to the risks or potential benefits of the research, in terms 
of severity or frequency. For example: 
• 
Safety monitoring indicates that a particular side effect is more severe, or more frequent than 
initially expected. 
• 
Change in FDA safety labeling or withdrawal from marketing of a drug, device, or biologic 
used in a research protocol. 
• 
Breach of confidentiality. 
• 
Change to the protocol taken without prior IRB review to eliminate apparent immediate hazard 
to a research participant. 
• 
Complaint of a participant when the complaint indicates unexpected risks, or the complaint 
cannot be resolved by the research team. 
• 
Protocol violation (meaning an accidental or unintentional deviation from the IRB approved 
protocol) that in the opinion of the investigator placed one or more participants at increased 
risk or affects the rights or welfare of subjects. 
 
Deaths that occur during the study should be reported within the IRB-specified time frame. 
For reportable deaths, the initial submission to the IRB may be made by contacting the IRB 
Director or Associate Director. The AE/Unanticipated Problem Form is required as a follow up to 
the initial submission. 
 
5.2.5.3 
FDA Notification by the Study Sponsor 
The Sponsor is required to report certain study events in an expedited fashion to the FDA. These 
written notifications of adverse events are referred to as IND safety reports. The sponsor must 
report an IND safety report as described in: 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U 
CM227351.pdf 

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The following describes the safety reporting requirements by timeline for reporting and associated 
type of event: 
 
• 
Within 7 Calendar Days any study event that is unexpected, fatal or life-threatening suspected 
adverse reaction. 
• 
Within 15 Calendar Days any study event that is unexpected, suspected adverse reaction that 
is serious, but not fatal or life-threatening -or- a previous adverse event that was not initially 
deemed reportable but is later found to fit the criteria for reporting, any finding from tests in 
laboratory animals that suggest a significant risk for human subjects including reports of 
mutagenicity, teratogenicity, or carcinogenicity or reports of significant organ toxicity at or 
near the expected human exposure. 
 
5.3 Medical Monitor 
The medical monitor will be a Sponsor physician or Sponsor-appointed physician with appropriate 
experience and Board Certification to oversee study conduct on the Sponsor’s behalf, consult with 
site investigators, review and synthesize safety information from the various clinical sites, and to 
apply study-stopping criteria. All decisions by the medical monitor affecting study conduct, 
including the application of study-stopping or dose-escalation rules, will be documented in the 
study record. 
 
5.4 Recording of Protocol Deviations 
If the impact on the protocol disrupts the study design, may affect the outcome (objectives), or 
compromises the safety and welfare of the subjects, the deviation must be reported to the medical 
monitor within three business days. Include the following information on the Sponsor-supplied 
exception/deviation form: protocol number, subject study number, description of the 
exception/deviation from protocol and rationale. Ensure all completed exception/deviation forms 
are signed by the Site Investigator and submitted to the Study Sponsor and medical monitor for 
review. Once approval of the exception request or acknowledgement of the deviation has been 
granted by the Sponsor and medical monitor, the exception or deviation will be submitted to IRB 
and all other applicable committees. 
 
Other deviations should be explained in a memo to file (example: a subject missing a visit is not 
an issue unless a critical/important treatment or procedure was missed and must have been 
performed at that specific time). 
 
5.5 Stopping Rules and Study Termination 
Premature termination of the clinical trial may occur because of a regulatory authority decision, 
change in opinion of the IRB or medical monitor. Additionally, recruitment may be stopped for 
reasons of particularly low recruitment, protocol violations, or inadequate data recording. 
Specifically, study will be stopped if: 
 
• 
Study Sponsor or a Regulatory Body decides for any reason that subject safety may be 
compromised by continuing the study. 
• 
The Sponsor decides to discontinue the development of the intervention to be used in this 
study. 

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The study will be paused if: 
 
• 
There is death that is reasonably attributed to study drug within the first 30 days after first 
infusion 
• 
Two subjects with Grade 4 adverse events to vital organs that are assessed as probably or 
definitely related to study drug within the 14days after last infusion 
 
If the study is paused for the reasons above, the PI and members of the study team will meet in 
person or by teleconference within 24 hours of the event to have a thorough discussion of the 
event. Meeting minutes capturing the review of any ongoing investigations, including next steps 
in the management of the subject and any proposed changes to the protocol will be forwarded to 
the medical monitor. If all parties agree as to the event resolution, then the pause will be lifted. If 
the study is paused for manufacturing reasons, the Sponsor will make recommendations for 
process improvements to be implemented. Pending successful completion of a process validation 
run, the manufacturing pause will be lifted. 

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Statistical Considerations 
Statistical analysis will be described in a separate Statistical Analysis Plan. 
 
Briefly, with respect to sample size: the primary endpoint will be the proportion of responders, 
i.e., patients who are MRD-negative with sCR at the Day 28 Visit. This is an open-label study, and 
the null hypothesis is that the responder rate will not differ from the natural rate of MRD-negative 
sCR at the end of consolidation, as observed in the literature. We determined that this natural rate 
is 10%.19,31,64,69-73 For purposes of power calculations, we assume that the response rate will be 
35%. With these assumptions, a sample size of 34 will provide 80% power to detect a one-tailed 
difference at the 95% confidence level. 

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Ethical Considerations 
7.1 General Issues 
This study is to be conducted according to US and international standards of Good Clinical Practice 
(FDA Title 21 part 312 and International Conference on Harmonization guidelines), applicable 
government regulations and Institutional research policies and procedures. 
 
This protocol and any amendments will be submitted to a properly constituted independent 
Institutional Review Board (IRB) for formal approval of the study conduct. The decision of the 
IRB concerning the conduct of the study will be made in writing to the investigator and a copy of 
this decision will be provided to the sponsor before commencement of this study. The investigator 
should provide a list of IRB members and their affiliations to the Sponsor. 
 
All subjects for this study will be provided a consent form describing this study and providing 
sufficient information for subjects to make an informed decision about their participation in this 
study. The consent form will be submitted with the protocol for review and approval by the IRB 
for the study. The formal consent of a subject, using the IRB-approved consent form, must be 
obtained before that subject is submitted to any study procedure. This consent form must be signed 
by the subject or legally acceptable surrogate, and the investigator-designated research 
professional obtaining the consent. 
 
7.2 Rationale for Subject Selection 
The patients to be entered in this protocol have MM which is an almost always incurable disease 
and therefore these patients have limited life expectancies. Subjects from both genders and all 
racial/ethnic groups are eligible for this study if they meet the eligibility criteria. To date, there is 
no information that suggests that differences in disease response would be expected in one group 
compared to another. It is not considered reasonable to administer a previously uncharacterized 
cell therapy to pregnant or lactating women. Children do not develop MM. Efforts will be made 
to extend accrual to a representative population, but in this preliminary study, a balance must be 
struck between patient safety considerations and limitations on the number of individuals exposed 
to potentially toxic and/or ineffective treatments on the one hand and the need to explore gender 
and ethnic aspects of clinical research on the other hand. If differences in outcome that correlate 
to gender or to ethnic identity are noted, accrual may be expanded, or a follow-up study may be 
written to investigate those differences more fully. 
 
7.3 Evaluation of Benefits and Risks 
Clinical trial summarized above demonstrated that targeting BCMA in MM by the CAR construct 
that will be used in the current protocol demonstrated mainly activity-associated toxicity and no 
off-target or on-target off-tumor effects. Furthermore, as noted above, Descartes-11 is expected to 
have even a better safety profile than the one used in that trial. Taken together, the potential 
benefits of the trial outweigh its risks. 

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7.4 Recordkeeping 
7.4.1 
Source Data 
Source data is all information, original records of clinical findings, observations, or other activities 
in a clinical trial necessary for the reconstruction and evaluation of the trial. Source data are 
contained in source documents. Examples of these original documents and data records include 
hospital records, clinical and office charts, laboratory notes, memoranda, subject diaries or 
evaluation checklists, pharmacy dispensing records, recorded data from automated instruments, 
copies or transcriptions certified after verification as being accurate and complete, microfiches, 
photographic negatives, microfilm or magnetic media, x-rays, subject files, and records kept at the 
pharmacy, at the laboratories, and at medico-technical departments involved in the clinical trial. 
 
7.4.2 
Case Report Forms 
The study case report form (CRF) is the primary data collection instrument for the study. All data 
requested on the CRF must be recorded. All entries will be entered into an electronic data capture 
system (eCRF). The Principal Investigator is responsible for assuring that the data entered into 
eCRF is complete, accurate, and that entry and updates are performed in a timely manner. 
 
7.4.3 
Confidentiality 
The investigator must ensure anonymity of the patients; patients must not be identified by names 
in any documents submitted to the sponsor. Signed informed consent forms and patient enrollment 
log must be kept strictly confidential to enable patient identification at the site. Information about 
study subjects will be kept confidential and managed according to the requirements of the Health 
Insurance Portability and Accountability Act of 1996 (HIPAA). Those regulations require a signed 
subject authorization informing the subject of the following: 
 
• 
What protected health information (PHI) will be collected from subjects in this study 
• 
Who will have access to that information and why 
• 
Who will use or disclose that information 
• 
The rights of a research subject to revoke their authorization for use of their PHI. 
 
If a subject revokes authorization to collect or use PHI, the investigator, by regulation, retains the 
ability to use all information collected prior to the revocation of subject authorization. For subjects 
that have revoked authorization to collect or use PHI, attempts should be made to obtain permission 
to collect at least vital status (i.e., that the subject is alive) at the end of their scheduled study 
period. 
 
7.4.4 
Records Retention 
It is the sponsor’s responsibility to retain study essential documents for at least 2 years after the 
last approval of a marketing application in their country and until there are no pending or 
contemplated marketing applications in their country or at least 2 years have elapsed since the 
formal discontinuation of clinical development of the investigational product. These documents 
should be retained for a longer period if required by a Regulatory Body. 

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Pharmaceutical Information 
Study drug will be provided by the Study Sponsor. For manufacturing and packaging details of the 
drug please see Section 1.3. FDA-approved Cyclophosphamide, Fludarabine and Tocilizumab will 
be sourced from commercial suppliers of the clinical site. Investigators will be referred to the 
approved labeling for those products. 

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Appendix A MANAGEMENT GUIDELINES FOR CAR 
T-CELL-RELATED TOXICITIES 
The clinical signs and symptoms of CAR T-related toxicities guide the grading and management 
of CRS and neurotoxicity. This protocol adapts management recommendations described by Lee 
et al.41 A copy of this reference will be provided to the investigator and staff are encouraged to 
review it prior to enrolling the first patient. The following is recommended: 
 
1. All patients with suspicion of CRS or fever above 37.9°C should be admitted for at least a 
24-hour observation. 
2. Infectious disease work-up with blood cultures should be initiated each time CRS is 
suspected. Empiric broad-spectrum intravenous antibiotics are recommended. 
3. Vital signs should be checked at least every 4 hours with strict urine input and output 
monitoring. 
4. Patients with poor oral intake should be started on intravenous fluids. Patients with 80% of 
their baseline systolic blood pressure (or if systolic BP<90mmHg) should be given a 0.5-
1 L fluid bolus. Fluid boluses can be repeated as needed; however, they should be kept to a 
minimum with a low threshold of starting low dose vasopressor as the capillary leak 
during CRS can lead to fluid overload. 
5. Patients should be transferred to the Intensive Care Unit (ICU) if: 
a. the patient’s systolic pressure does not respond to the first fluid bolus; 
b. the patient requires 2 or more fluid boluses within 24 hours; 
c. the patient’s heart rate remains above 125/min for at least 4 hours; 
d. the patient’s supplemental oxygen requirement is more than 40% FiO2; or 
e. the patient has >Grade 2 neurotoxicity. 
6. Patients admitted to the ICU should have the following: 
a. vital signs checked every 2 hours; 
b. cardiac enzymes, ECG and echocardiogram evaluation; 
c. if systolic blood pressure is below 75% of baseline or below 85 mmHg, 
norepinephrine should be started; 
d. CBC should be checked twice a day and cytopenias should be treated as follows: 
i. blood transfusion to keep Hgb above 8.0 g/dL; 
ii. platelet transfusion to keep platelet above 20k; 
iii. growth factors for neutropenia can be started if ANC is below 1000/µL. 
Filgrastim is recommended due to a shorter half-life compared with 
pegfilgrastim. 
7. Tocilizumab at the FDA-approved dose for CRS should be administered in the following 
circumstances: 
a. grade 3 CRS; 
b. grade 2 CRS that is not resolving within 72 hours; or 
grade 2 CRS in the context of other co-morbidities or old age. 

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8. TOCILIZUMAB SHOULD NOT BE GIVEN FOR ISOLATED NEUROTOXOCITY. 
9. If the patient does not respond to tocilizumab within 12 hours, a repeat dose of tocilizumab 
can be given. If  the  patient  does  not  respond  to  the  second  dose,  corticosteroids  
(i.e. methylprednisolone 1mg/kg every 12 hours) should be prescribed. 
10. Patients who are recovering from CRS should not be discharged until they are afebrile for 
at least 24 hours. 
11. If neurotoxicity is suspected, the patient should be evaluated with the Immune Effector 
Cell Encephalopathy (ICE) scale41. Patients with Grade 2 neurotoxicity should get a 
neurology consult and thorough evaluation, e.g., with lumbar puncture and MRI, for other 
etiologies. 
12. Patients who have Descartes-11 related neurotoxicity (except for headache) should receive 
dexamethasone in the following situations at 10mg/kg every 4-6 hours until symptoms 
regress to Grade 1: 
a. grade 3 neurotoxicity lasting for 24 hours; 
b. grade 4 neurotoxicity; or 
c. any generalized seizure (in conjunction with other anti-seizure therapies). 

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• 
If the patient is on anticoagulation therapy, there should be no contraindication for holding 
the drug during the apheresis procedure 
8. If the subject is actively on a medication for treatment of an oncologic disease, there should 
be a minimum of 7 days between the last dose and the leukapheresis procedure. If the agent 
is a monoclonal antibody then wash-out should be minimum of 21 days and if it is an 
experimental agent then it should be 5 half-lives. 
 
 
2.2 Exclusion Criteria 
1. Major chronic illness that is not well managed at the time of study entry and in the opinion of 
the investigator may increase the risk to the patient. 
2. Any other laboratory abnormality that, in the opinion of the investigator, may jeopardize the 
subject’s ability to participate in the study. 
3. Any active significant cardiac or pulmonary disease. Note: Patients with asthma and COPD 
controlled with inhaled medications are allowed. 
4. Treatment with any investigational agent within 4 weeks of screening or 5 half-lives of the 
investigational drug (whichever is longer). 
5. History of significant recurrent infections or any active infection at screening visit. 
6. Patient is pregnant or lactating. 
 
 
2.3 Screening, Evaluation and Enrollment 
2.3.1 
Recruitment of Patients 
Subjects who are enrolled into a study using Descartes products will be referred for cell collection. 
 
2.3.2 
Screening Evaluation 
Please refer to Section 4.1.1 for Screening visit evaluations. 
 
2.3.3 
Enrollment 
To enroll a subject on this study, the following documents are required: 
• 
Copy of signed/dated consent and HIPAA Authorization 
• 
Source documentation to confirm enrollment/eligibility 

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Before leukapheresis, the following assessments should be completed: 
• 
Vital signs (including pulse oximetry) 
• 
Concomitant medications 
• 
CBC 
 
After leukapheresis, the following assessments should be completed: 
• 
Adverse event review and evaluation 
• 
CBC 
 
 
3.3 Management of Possible Toxicities 
All toxicities should be managed based on institutional guidelines and per apheresis physician’s 
discretion. Below are recommendations and deviations from them will not be considered as 
protocol deviation. 
 
3.3.1 
Hypocalcemia 
Hypocalcemia is a decrease in calcium levels. Hypocalcemia is a response to citrate toxicity, which 
can result with large volume leukapheresis. Symptoms of hypocalcemia include numbness and 
tingling, especially in the hands, feet, and around the mouth. Hypocalcemia can also cause painful 
muscle spasms that can be alleviated with calcium-rich foods and supplements. If symptoms 
persist during the procedure, the following protocols are advised: slowing the procedure, 
decreasing the amount of anticoagulation, and administering oral or intravenous calcium 
supplementation. 
 
3.3.2 
Vasovagal Response 
Few subjects experience episodes of vasovagal responses such as lightheadedness or fainting. 
These occurrences are induced by extracorporeal blood flow and discomfort and/or fear of 
venipunctures. Major vasovagal episodes have been reported from patients receiving therapeutic 
leukapheresis in research for treatment of polymyositis and dermatomyositis, diseases of the 
muscle tissue. 
 
3.3.3 
Blood Loss 
Varying, minor degrees of RBC or platelet loss have been reported. Devices separate and return 
blood according to different manufacturer settings that may have an influence on accounted 
hemoglobin or hematocrit levels. Significant blood loss, however, has not been reported. Patients 
with a history of anemia or thrombocytopenia should proceed leukapheresis treatments with 
caution. 
 
3.3.4 
Discomfort at Venipuncture Site 
Discomfort, bruising, bleeding, or swelling at the venipuncture site may occur. These minor 
interactions may occur with any venipuncture procedure and is usually dependent on venous 

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structural integrity. Routine procedures are in place at each facility to help minimize the occurrence 
of these discomforts and, in some cases, an alternate venipuncture site may be utilized. 
 
3.3.5 
Infection 
Infection, although rare, can occur at the venipuncture site due to cannula or catheter placement. 
Infection is minimized with proper sterilization standards and has been significantly reduced with 
disposable collection and storage equipment. 
 
4 Safety, Adver se Events, Pr otocol Deviation and Stopping 
Rules 
4.1 Definitions 
4.1.1 
Adverse Events (AE) 
An adverse event (AE) is defined as any reaction, side effect, or untoward event that occurs during 
the clinical trial associated with the use of a test article in humans, whether or not the event is 
considered related to the treatment or clinically significant. For this study, AEs will include events 
reported by the patient, as well as clinically significant abnormal findings on physical examination 
or laboratory evaluation. A new illness, symptom, sign or worsening of a pre-existing condition or 
abnormality is considered an AE. An abnormal laboratory value will be considered an AE if the 
laboratory abnormality is characterized by any of the following: 
• 
Results in discontinuation from the study 
• 
Is associated with clinical signs or symptoms 
• 
Requires treatment or any other therapeutic intervention 
• 
Is associated with death or another serious adverse event, including hospitalization. 
• 
Is judged by the Investigator to be of significant clinical impact 
 
All AEs, including clinically significant abnormal findings on laboratory evaluations, regardless 
of severity, will be followed until satisfactory resolution. 
 
4.1.2 
Suspected Adverse Reaction 
Suspected adverse reaction means any adverse event for which there is a reasonable possibility 
that the test article caused the adverse event. For the purposes of IND safety reporting, “reasonable 
possibility” means there is evidence to suggest a causal relationship between the test article and 
the adverse event. A suspected adverse reaction implies less certainty about causality than adverse 
reaction, which means any adverse event caused by a test article. 
 
4.1.3 
Serious Unexpected Adverse Reaction (SUSAR) 
An adverse event or suspected adverse reaction is considered "unexpected" if it is not listed in the 
investigator brochure or is not listed at the specificity or severity that has been observed; or, if an 
investigator brochure is not required or available, is not consistent with the risk information 
described in the general investigational plan or elsewhere in the current application. "Unexpected" 

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also refers to adverse events or suspected adverse reactions that are mentioned in the investigator 
brochure as occurring with a class of the test article or as anticipated from the pharmacological 
properties of the drug but are not specifically mentioned as occurring with the test article under 
investigation. 
 
4.1.4 
Serious Adverse Event (SAE) 
An adverse event or suspected adverse reaction is considered serious if in the view of the 
investigator or the sponsor, it results in any of the following: 
 
• 
Persistent or significant incapacity or substantial disruption of the ability to conduct normal 
life functions 
• 
A congenital anomaly/birth defect 
• 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered a SAE experience when, based upon appropriate medical 
judgment, they may jeopardize the patient or subject and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition. 
 
 
4.1.5 
Protocol Deviation 
A one-time, unintentional action or process that departs from the IRB-approved study protocol, 
involving one incident and identified retrospectively, after the event occurred. Any leukapheresis- 
related failure or deviation will be recorded, even if it does not constitute a per-protocol AE. 
 
4.2 Recording of Adverse Events 
4.2.1 
Adverse Event Recording Period 
The study period during which adverse events must be reported is normally defined as the period 
from the signing of consent to the leukapheresis completion. Serious Adverse Event reporting 
period starts with leukapheresis and ends 72 hours after the procedure. 
 
All unresolved adverse events should be followed by the investigator until the events are resolved, 
the subject is lost to follow-up, or the adverse event is otherwise explained. At the last scheduled 
visit, the investigator should instruct each subject to report any suspected adverse event(s) that 
might reasonably be related to participation in this study. The investigator should notify the 
Sponsor of any death or adverse event occurring at any time after a subject has discontinued or 
terminated study participation if the event may reasonably be related to this study. The Sponsor 
should also be notified if the investigator should become aware of the development of cancer or of 
a congenital anomaly in a subsequently conceived offspring of a subject that has participated in 
this study. 
 
4.2.2 
Hospitalization, Prolonged Hospitalization or Surgery 
Any adverse event that results in hospitalization or prolonged hospitalization should be 
documented and reported as a serious adverse event unless specifically instructed otherwise as 
below. Any condition responsible for surgery should be documented as an adverse event if the 

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condition meets the criteria for an adverse event. Neither the condition, hospitalization, prolonged 
hospitalization, nor surgery are reported as an adverse event in the following circumstances: 
 
• 
Hospitalization or prolonged hospitalization for diagnostic or elective surgical procedures for 
a preexisting condition. Surgery should not be reported as an outcome of an adverse event if 
the purpose of the surgery was elective or diagnostic and the outcome was uneventful. 
• 
Hospitalization or prolonged hospitalization for therapy of the target disease of the study, 
unless there is clinical worsening or an increase in frequency of hospital admissions as 
judged by the clinical investigator. 
 
 
4.2.3 
Pregnancies 
To ensure patient safety, each pregnancy in a patient on study treatment must be reported to the 
Sponsor within 24 hours of learning of its occurrence. The pregnancy must be followed up to 
determine outcome, including spontaneous or voluntary termination, details of the birth, and the 
presence or absence of any birth defects, congenital abnormalities, or maternal and/or newborn 
complications. Pregnancy should be recorded on a Clinical Study Pregnancy Form and reported 
by the investigator to the Sponsor. Pregnancy follow-up should be recorded on the same form and 
must include an assessment of the possible relationship to the study treatment of any pregnancy 
outcome. Any SAE experienced during pregnancy must be reported on the SAE Report Form. 
Pregnancy outcomes must be collected for the female partners of any males who took study 
treatment in this study. Consent to report information regarding these pregnancy outcomes should 
be obtained from the mother. 
 
4.2.4 
Recording of Adverse Events 
Information on all adverse events should be recorded immediately in the source document, and in 
the appropriate adverse event module of the case report form (CRF). All clearly related signs, 
symptoms, and abnormal diagnostic procedures results should be recorded in the source document, 
though should be grouped under one diagnosis. To the extent possible, adverse events should be 
recorded as a diagnosis and symptoms used to make the diagnosis recorded within the diagnosis 
event. Do not list symptoms if a diagnosis can be assigned. 
 
Adverse events (including lab abnormalities that constitute AEs) should be described using a 
diagnosis whenever possible, rather than individual underlying signs and symptoms. When a clear 
diagnosis cannot be identified, each sign or symptom should be reported as a separate Adverse 
Event. The clinical course of each event should be followed until resolution, stabilization, or until 
it has been determined that the study treatment or participation is not the cause. As detailed as 
possible, each adverse event should be evaluated to determine: 
 
• 
The severity grade (CTCAE Version 5.0 Grade 1-5) 
• 
Its duration (start and end dates) 
• 
Its relationship to the leukapheresis procedure Is there a reasonable possibility that the AE is 
related to procedure- No (unrelated) or Yes. If yes- is the event definitely, probably, possibly 
or unlikely related 

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• 
Action taken with respect to study or investigational treatment (none, dose adjusted, 
temporarily interrupted, permanently discontinued, unknown, not applicable) 
• 
Whether medication or therapy taken (i.e., no concomitant medication/non-drug therapy, 
concomitant medication/non-drug therapy) 
• 
Whether it is serious, as defined in Section 5.1. 
 
All adverse events should be treated appropriately. If a concomitant medication or non-drug 
therapy is given, this action should be recorded on the Adverse Event CRF. Adverse events should 
be entered into the eCRF system within 10 working days from the knowledge of the event took 
place. Once an adverse event is detected, it should be followed until its resolution or until it is 
judged to be permanent, and assessment should be made at each visit (or more frequently, if 
necessary) of any changes in severity, the suspected relationship to the study treatment, the 
interventions required to treat it, and the outcome. 
 
Progression of malignancy (including fatal outcomes), documented appropriately in the medical 
records, should not be reported as a serious adverse event. Adverse events that occur concurrently 
with the progression of malignancy but that are not related to disease progression (i.e., deep vein 
thrombosis) will be reported as an adverse event as described above. 
 
4.2.5 
SAE and SUSAR Reporting 
To ensure patient safety, every SAE and SUSAR, regardless of suspected causality, occurring 
during the adverse event reporting period must be reported to the Sponsor within 24 hours of 
learning of its occurrence. Recurrent episodes, complications, or progression of the initial SAE 
must be reported as follow-up information is received. An SAE occurring at a different time 
interval or otherwise considered completely unrelated to a previously reported one should be 
reported separately as a new event. 
 
4.2.5.1 
Study Sponsor Notification by the Investigator 
Any SUSAR and SAE as defined in Section 4.1 must be reported to the Sponsor by email or fax 
within 24 hours of knowledge of the event. To the extent possible, adverse events should be 
recorded as a diagnosis. Do not list symptoms if a diagnosis can be assigned. At the time of the 
initial notification, a serious adverse event (SAE) report form should be filled. Following 
parameters will be asked in the form: 
 
• 
Subject information 
• 
A description of the event (if there is a diagnosis, it should be included) 
• 
Date of onset 
• 
Current status 
• 
Whether study treatment was discontinued 
• 
The reason why the event is classified as serious 
• 
Investigator assessment of the association between the event and procedure 
• 
Concomitant medications when the event happened 
• 
Narrative summary of the event 

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Follow-up information on this event should be reported when received. The follow-up information 
should describe 1) whether the event has resolved or continues, 2) if and how it was treated, and 
3) whether the patient continued or withdrew from study participation. 
 
4.2.5.2 
IRB Notification by the Investigator 
Following events should be reported to IRB: 
 
• 
Information that indicates a change to the risks or potential benefits of the research, in terms 
of severity or frequency. For example: 
• 
Safety monitoring indicates that a particular side effect is more severe, or more frequent than 
initially expected. 
• 
Breach of confidentiality. 
• 
Change to the protocol taken without prior IRB review to eliminate apparent immediate 
hazard to a research participant. 
• 
Complaint of a participant when the complaint indicates unexpected risks, or the complaint 
cannot be resolved by the research team. 
• 
Protocol violation (meaning an accidental or unintentional deviation from the IRB approved 
protocol) that in the opinion of the investigator placed one or more participants at increased 
risk or affects the rights or welfare of subjects. 
 
Deaths that occur during the study should be reported within the IRB-specified time frame. 
For reportable deaths, the initial submission to the IRB may be made by contacting the IRB 
Director or Associate Director. The AE/Unanticipated Problem Form is required as a follow up to 
the initial submission. 
 
5. Ethical Consider ations 
5.1 General Issues 
This study is to be conducted according to US and international standards of Good Clinical Practice 
(FDA Title 21 part 312 and International Conference on Harmonization guidelines), applicable 
government regulations and Institutional research policies and procedures. 
 
This protocol and any amendments will be submitted to a properly constituted independent 
Institutional Review Board (IRB) for formal approval of the study conduct. The decision of the 
IRB concerning the conduct of the study will be made in writing to the investigator and a copy of 
this decision will be provided to the sponsor before commencement of this study. The investigator 
should provide a list of IRB members and their affiliations to the Sponsor. 
 
All subjects for this study will be provided a consent form describing this study and providing 
sufficient information for subjects to make an informed decision about their participation in this 
study. The consent form will be submitted with the protocol for review and approval by the IRB 
for the study. The formal consent of a subject, using the IRB-approved consent form, must be 
obtained before that subject is submitted to any study procedure. This consent form must be signed 

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by the subject or legally acceptable surrogate, and the investigator-designated research 
professional obtaining the consent. 
 
5.2 Evaluation of Benefits and Risks 
Cells collected from subjects enrolled into this protocol will be used to manufacture Descartes-11. 
There is no expected direct benefit of the procedure. These subjects will be identified by the 
Principal Investigator of the Sponsor’s clinical trial at a site that has an open treatment protocol 
involving Descartes-11. Subjects identified for the Descartes-11 clinical trial protocols have either 
symptomatic disease that is refractory to standard of care or they are intolerant to approved 
regimens for their disease and therefore in need of additional investigational treatment. 
 
The risks associated with leukapheresis are associated with the decrease in WBC count, interaction 
with anticoagulation solutions, and the actual venipuncture site for withdrawal and return of blood, 
all of which can be identified and treated easily at certified apheresis centers. 
 
5.3 Confidentiality 
The investigator must ensure anonymity of the patients; patients must not be identified by names 
in any documents submitted to the sponsor. Signed informed consent forms and patient enrollment 
log must be kept strictly confidential to enable patient identification at the site. Information about 
study subjects will be kept confidential and managed according to the requirements of the Health 
Insurance Portability and Accountability Act of 1996 (HIPAA). Those regulations require a signed 
subject authorization informing the subject of the following: 
 
• 
What protected health information (PHI) will be collected from subjects in this study 
• 
Who will have access to that information and why 
• 
Who will use or disclose that information 
• 
The rights of a research subject to revoke their authorization for use of their PHI. 
 
If a subject revokes authorization to collect or use PHI, the investigator, by regulation, retains the 
ability to use all information collected prior to the revocation of subject authorization. For subjects 
that have revoked authorization to collect or use PHI, attempts should be made to obtain permission 
to collect at least vital status (i.e., that the subject is alive) at the end of their scheduled study 
period.