## Protocol Section
### Identification Module
**NCT ID:** NCT06420167

**Acronym:** FLORAL

**Brief Title:** DapagliFLOzin in Renal AL Amyloidosis (FLORAL)

**Official Title:** DapagliFLOzin in Renal AL Amyloidosis (FLORAL)

#### Organization Study ID Info
**ID:** 2023-074
#### Organization
**Class:** OTHER
**Full Name:** Barbara Ann Karmanos Cancer Institute
### Status Module
#### Completion Date
**Date:** 2027-04

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-17

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-14

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-04

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-05

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-17
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-14
**Study First Submit QC Date:** 2024-05-14
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Jeffrey Zonder

#### Responsible Party

**Investigator Affiliation:** Barbara Ann Karmanos Cancer Institute

**Investigator Full Name:** Jeffrey Zonder

**Investigator Title:** Principal Investigator, Multiple Myeloma Multidisciplinary team leader, M.D.

**Type:** SPONSOR_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Is US Export:** False

### Description Module

**Brief Summary:** The goal of this clinical trial is to learn if an oral drug called dapagliflozin is safe and can reduce high protein levels in the urine of patients with renal amyloid light-chain (AL) amyloidosis using a decentralized study design.

Participants will be:

* screened for the trial via an online platform
* contacted by study personal to obtain electronic consent
* enrolled in the trial if eligible and consented
* contacted by study personal for further instructions and directions
* sent dapagliflozin oral medication (supplied by the site pharmacy)
* followed up regularly with the study team via telemedicine or other online avenues
* monitored using lab work, inquiries about side effects and assessment of protocol adherence at 1 month, 3 months and 6 months
* continue treatment for 6 months

**Detailed Description:** 1. Participants are recruited by one of the following methods:

   1. Self-referral through the website
   2. Receiving recruitment materials from their provider.
2. Participant visits the prescreening website.

   1. High level prescreening questions are answered by the participant.
   2. If appropriate based on answers to the questions, the participant may provide their contact information for follow up by the study team.
3. Study team contacts potential participants to review the study and explain next steps
4. Participant is provided with the link and password to view the video and sign the consent via Adobe Sign
5. An investigator will meet virtually with the participant to obtain medical history information, concomitant medications, and performance status (screening visit)
6. Once the participant passes screening in step 5, an order will be sent to the participant for the remaining screening labs to be done at a local laboratory that is covered by their insurance
7. The lab will fax results to the site
8. After review of eligibility and the study team will proceed with enrolling the participant if appropriate
9. The participant will proceed to the baseline visit (telehealth for any portion that can be done via phone/video and order for lab tests as previously described) if needed to comply with the protocol calendar/window.
10. The participant is approved to begin dosing by the investigator
11. The site will dispense via mail the following:

    1. 4 month's supply of Dapagliflozin
    2. A self-addressed envelope for return of the diary and pill bottles at the end of the dosing period
    3. A weighing scale (if required)
12. Dosing compliance will be checked during initial study treatment via sharing of pill accountability data or screenshot of paper pill diary
13. If clinically indicated, labs will be ordered and run more frequently to assess for toxicity.
14. Visits 3, 4, and 5 will be conducted in the same manner as described above.
15. All pill bottles and diaries (if paper version is used) will be returned via the provided envelope

### Conditions Module

**Conditions:**

- Renal AL Amyloidosis

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 20

**Type:** ESTIMATED

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Dapagliflozin 10mg orally, daily for 6 months

**Intervention Names:**

- Drug: Dapagliflozin

**Label:** Dapagliflozin

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Dapagliflozin

**Description:** 10mg orally once daily

**Name:** Dapagliflozin

**Other Names:**

- BMS-512148

- Forxiga® / Farxiga®

**Type:** DRUG

### Outcomes Module

#### Other Outcomes

**Description:** A patient's status will be recorded as 'yes' if any of the following three events occur at any time during the 6 months of study therapy: a sustained ≥50% decline in estimated glomerular filtration rate (eGFR); the onset of dialysis-requiring end- stage renal disease (ESRD); or death from a renal disease-related or cardiovascular cause. Otherwise, the status will be marked as 'no'.

**Measure:** Proportion of patients experiencing any of the following: (1) sustained decline in eGFR, (2) onset of ESRD, or (3) death from a renal disease-related or cardiovascular cause.

**Time Frame:** Up to Month 6

**Description:** The onset of ESRD in patients with Pavia Renal Stage II or III involvement will be recorded as binary (yes vs. no).

**Measure:** Incidence rate of developing dialysis dependent ESRD in patients with Pavia Renal AL Stage II or III involvement.

**Time Frame:** Up to Month 6

#### Primary Outcomes

**Description:** A patient will be considered to have achieved the desired urine protein reduction if a 30% reduction in 24-hour albuminuria occurs at any point during the six-month period from the initiation of dapagliflozin therapy. The proportion of patients achieving this reduction will be calculated as the ratio of the total number of patients who experienced the reduction to the total number of evaluable patients.

**Measure:** Proportion of patients achieving 30% reduction in daily proteinuria.

**Time Frame:** Up to Month 6

#### Secondary Outcomes

**Description:** The completion rate of tele-visits, including post-trial feedback, will be calculated as the ratio of completed tele-visits to scheduled tele-visits.

**Measure:** Completion rate of tele-visits

**Time Frame:** Up to Month 6

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Provision of signed and dated informed consent form.
* Stated willingness to comply with study procedures, including remote telehealth consultations with the study team, confirming availability, and agreeing to use mobile/web applications for study purposes.
* Age ≥18 years.
* Histopathologic diagnosis of renal AL amyloidosis confirmed by biopsy of any tissue and evidence of \>1.0 g/day proteinuria without any other identifiable cause.
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0, 1 or 2.
* Plateau in any renal response (i.e., reduction in proteinuria) for at least 3 months prior to enrollment, as determined by the enrolling physician.
* Residence in the state of Michigan.

Exclusion Criteria:

* Either ongoing first line induction with anti-plasma cell therapy or ongoing post- induction maintenance for \<6 months prior to enrollment.
* Diagnosis of symptomatic multiple myeloma, including presence of lytic bone disease, plasmacytomas, ≥60% plasma cells in the bone marrow, or hypercalcemia, either currently or in the past.
* Women of child-bearing potential (i.e., those who have not undergone chemical or surgical sterilization or are not postmenopausal) and who are unwilling to use a medically accepted and reliable form of contraception while participating in the study and for 2 weeks following the last dose of study medication, as determined by the investigator, or have a positive pregnancy test at the time of enrolment or are currently breastfeeding.
* Known allergic reactions to components of the dapagliflozin.
* Treatment requiring type 1 or type 2 diabetes mellitus.
* Baseline eGFR \<25 mL/min/1.73m2.
* Acute or chronic liver disease with severe impairment of liver function (e.g., ascites, esophageal varices or coagulopathy)
* Current or previous use of any SGLT2i.
* Initiation or dose modification of angiotensin converting enzyme inhibitors (ACE inhibitors) and angiotensin receptor blockers (ARBs) \<3 months prior to enrollment.
* Active malignancy requiring treatment (other than AL amyloidosis and non-melanoma skin cancers).

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** Houdec@karmanos.org

**Name:** Christiane Houde

**Phone:** 3135768673

**Role:** CONTACT

**Contact 2:**

**Email:** zonderj@karmanos.org

**Name:** Jeffery Zonder, M.D.

**Phone:** 3135768732

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Detroit

**Contacts:**

***Contact 1:***

- **Email:** Houdec@karmanos.org

- **Name:** Christiane Houde

- **Phone:** 313-576-8673

- **Role:** CONTACT

***Contact 2:***

- **Email:** zonderj@karmanos.org

- **Name:** Jeffery Zonder

- **Phone:** 3135768732

- **Role:** CONTACT

***Contact 3:***

- **Name:** Jeffery Zonder, M.D.

- **Role:** PRINCIPAL_INVESTIGATOR

***Contact 4:***

- **Name:** Andrew Kin, M.D.

- **Role:** SUB_INVESTIGATOR

***Contact 5:***

- **Name:** Aditi Sharma, M.D.

- **Role:** SUB_INVESTIGATOR

***Contact 6:***

- **Name:** Joel Topf, M.D.

- **Role:** SUB_INVESTIGATOR

**Country:** United States

**Facility:** Karmanos Cancer Institute

**State:** Michigan

**Zip:** 48201

#### Overall Officials

**Official 1:**

**Affiliation:** Barbara Ann Karmanos Cancer Institute

**Name:** Jeffery Zonder, M.D.

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000057165

- Term: Proteostasis Deficiencies

- ID: D000008659

- Term: Metabolic Diseases

- ID: D000054219

- Term: Neoplasms, Plasma Cell

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

- ID: D000008232

- Term: Lymphoproliferative Disorders

- ID: D000007160

- Term: Immunoproliferative Disorders

- ID: D000007154

- Term: Immune System Diseases

- ID: D000010265

- Term: Paraproteinemias

### Condition Browse Module - Browse Branches

- Abbrev: BC18

- Name: Nutritional and Metabolic Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC20

- Name: Immune System Diseases

- Abbrev: BC15

- Name: Blood and Lymph Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M4021

- Name: Amyloidosis

- Relevance: HIGH

- As Found: Amyloidosis

- ID: M1483

- Name: Immunoglobulin Light-chain Amyloidosis

- Relevance: HIGH

- As Found: AL Amyloidosis

- ID: M28747

- Name: Proteostasis Deficiencies

- Relevance: LOW

- As Found: Unknown

- ID: M11639

- Name: Metabolic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M27588

- Name: Neoplasms, Plasma Cell

- Relevance: LOW

- As Found: Unknown

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M11225

- Name: Lymphoproliferative Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M10206

- Name: Immunoproliferative Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M10200

- Name: Immune System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M13178

- Name: Paraproteinemias

- Relevance: LOW

- As Found: Unknown

- ID: T254

- Name: AL Amyloidosis

- Relevance: HIGH

- As Found: AL Amyloidosis

### Condition Browse Module - Meshes

- ID: D000075363

- Term: Immunoglobulin Light-chain Amyloidosis

- ID: D000000686

- Term: Amyloidosis

### Intervention Browse Module - Ancestors

- ID: D000077203

- Term: Sodium-Glucose Transporter 2 Inhibitors

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000007004

- Term: Hypoglycemic Agents

- ID: D000045505

- Term: Physiological Effects of Drugs

### Intervention Browse Module - Browse Branches

- Abbrev: Hypo

- Name: Hypoglycemic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M348449

- Name: Dapagliflozin

- Relevance: HIGH

- As Found: COPD

- ID: M1691

- Name: Sodium-Glucose Transporter 2 Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M10054

- Name: Hypoglycemic Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: C000529054

- Term: Dapagliflozin

### Misc Info Module

- Version Holder: 2024-05-31
