A Open-label Study of Ultra-High Dose Dexamethasone for Relapsed Multiple Myeloma

STUDY OBJECTIVES

Primary objective:

• Determine antitumor activity of ultrahigh dose dexamethasone (UHDD) as monotherapy in
relapsed multiple myeloma.

Secondary objectives:

- Characterize the safety and tolerability of UHDD as monotherapy in patients with
relapsed multiple myeloma.

- Determine the progression free survival amongst responders.

- Determine the subset of patients in whom UHDD can be used as monotherapy for treatment
of relapsed multiple myeloma

STUDY ENDPOINTS

Primary endpoint: To determine the anti-tumor activity of UHDD as monotherapy in patients
with relapsed multiple myeloma as measured by the International Myeloma Working Group (IMWG)
response criteria:

- Change from baseline in M protein component.

- Objective response rate (complete response [CR] + partial response [PR]) assessed
according to IMWG response criteria.

- Disease control rate (CR+PR+stable disease [SD]).

Secondary endpoints:

- Safety and tolerability of UHDD

- Progression free survival.

- Characteristics of patients responding to UHDD.

Inclusion Criteria:

1. Relapsed multiple myeloma (MM) with measurable disease parameters according to the
International Myeloma Working Group (IMWG) Criteria for the Diagnosis of Multiple
Myeloma

2. Relapsed is defined as the development of disease progression following the
achievement of stable disease (SD), partial response (PR), very good partial response
(VGPR), complete response (CR) or stringent complete response (sCR) to the most
recent anti-myeloma regimen

3. Received ≥ 2 prior regimen for MM

4. The patient or the patient's legal representative is able to understand the risks of
the study and provide signed informed consent and authorization to use protected
health information (in accordance with national and local privacy regulations)

5. ≥18 years of age

6. Karnofsky Performance Status score of ≥70

7. Able to adhere to the study visit schedule and other protocol requirements in the
Investigator's opinion

8. Adequate hepatic function, as evidenced by serum bilirubin values <6.0 mg/dL and
serum alanine transaminase (ALT) and/or aspartate transaminase (AST) values <3 × the
upper limit of normal (ULN) of the local laboratory reference range. (Patients with
isolated elevations in alkaline phosphatase [ALP] <5 × ULN in the presence of bony
disease are not excluded from participating in the study)

9. If a female participant is of childbearing potential, she must have a negative
pregnancy test (urine or serum) at baseline (Cycle 1, Day 0). (A female participant
is considered to be NOT of childbearing potential if she has undergone bilateral
oophorectomy or if she has been menopausal without a menstrual period for 12
consecutive months)

Exclusion Criteria:

1. Received any of the following therapies: Radiotherapy within 2 weeks of Cycle 1 Day
1; Systemic therapy within 3 weeks of Cycle 1 Day 1

2. Prior peripheral autologous stem cell transplant within 12 weeks of Cycle 1 Day 1

3. Prior allogeneic stem cell transplant

4. Active systemic infection requiring treatment

5. Active malignancy (the following are allowable: patients with basal cell carcinoma of
the skin; superficial carcinoma of the bladder; carcinoma of the prostate with a
current prostate-specific antigen <0.1 ng/mL; or cervical intraepithelial neoplasia).

6. Known or suspected human immunodeficiency virus (HIV) positive or hepatitis B surface
antigen-positive status or is known or suspected to have an active hepatitis C
infection

7. If female, patient is lactating

8. History of significant cardiovascular, neurological, endocrine, gastrointestinal,
respiratory, or inflammatory illness that could preclude study participation, pose an
undue medical hazard, or interfere with the interpretation of the study results,
including, but not limited to, patients with:

1. Congestive heart failure (New York Heart Association [NYHA] Class 3 or 4

2. Unstable angina

3. Cardiac arrhythmia

4. Recent (within the preceding 6 months) myocardial infarction or stroke

5. Hypertension requiring >3 medications for adequate control

6. Chronic obstructive pulmonary disease

9. History of uncontrolled diabetes mellitus (Type I or II) (Hemoglobin A1C>8.5)

10. Any other medical, psychiatric, or social condition that would preclude participation
in the study, pose an undue medical hazard, interfere with the conduct of the study,
or interfere with interpretation of the study results

11. History of adverse reaction to dexamethasone or other corticosteroids.

12. History of allergic reaction attributable to any of the required prophylactic
medications (proton pump inhibitor (PPI), fluconazole, trimethoprim-sulfamethoxazole)
or reasonable alternative medications

13. Inability to monitor glucose at home with glucometer if glucose is found to be
abnormal at any study center visit

14. Known or suspected AL Amyloidosis

15. Currently receiving an investigational agent for any reason