Evomela Preparative Regimen for Autologous Hematopoietic Stem Cell Transplantation (AutoSCT) for Multiple Myeloma (MM)

Study Groups:

If you are found to be eligible to take part in this study, you will be randomly assigned (as
in the flip of a coin) to 1 of 2 study groups. This is done because no one knows if one study
group is better, the same, or worse than the other group. You will have an equal chance of
being assigned to either group.

- If you are in Group 1, you will receive Evomela by vein over 30-60 minutes.

- If you are in Group 2, you will receive Evomela by vein over 8-9 hours.

Up to 2 dose levels will be tested in each group. You will be assigned to a dose level of
Evomela based on when you join this study. Up to 15 participants will be enrolled at each
dose level in each group. The first sets of participants will receive the lowest dose level.
Each new set will receive a higher dose than the set before it, if no intolerable side
effects were seen. This will continue until the highest tolerable dose of Evomela is found.

Study Drug Administration:

You will first have a central venous catheter (CVC) placed. A CVC is a sterile flexible tube
that will be placed into a large vein while you are under local anesthesia. Your doctor will
explain this procedure to you in more detail, and you will be required to sign a separate
consent form.

You will receive Evomela to help prepare your body for the stem cell infusion. The day you
receive the stem cell transplant is called Day 0. The days before you receive your stem cell
transplant are called minus days. The days after you receive the stem cell transplant are
called plus days.

On Days -5, -4, and -3, you will receive palifermin by vein over about 30 seconds each day as
an outpatient to help decrease the risk of side effects in the mouth and throat.

On Day -3, you will be admitted to the hospital and given fluids by vein to hydrate you.

On Day -2, you will receive Evomela by vein over 30-60 minutes or 8-9 hours.

On Day -1, you will rest.

Since Evomela may cause mouth blisters/sores, you will be instructed to keep crushed ice in
your mouth.

If you will receive Evomela over 30-60 minutes, you will be instructed to keep ice in your
mouth starting 30 minutes before the infusion, during the infusion, and for at least 2 hours
after the end of the infusion.

If you will receive Evomela over 8-9 hours, you will be instructed to keep ice in your mouth
starting 30 minutes before the infusion, during the infusion (as long as you can tolerate
it), and for at least 2 hours after the end of the infusion.

On Day 0, you will receive the stem cell transplant by vein over about 30-60 minutes.

On Days +1, +2, and +3, you will receive palifermin by vein over about 30 seconds each day to
help decrease the risk of side effects in the mouth and throat.

Starting on Day +5, you will receive G-CSF (filgrastim) as an injection just under your skin
1 time each day until your blood cell levels return to normal. The study doctor will discuss
this with you, including how filgrastim is given and its risks.

You will be given standard drugs to help decrease the risk of side effects. You may ask the
study staff for information about how the drugs are given and their risks.

Length of Study:

Your participation on this study will be over when you have completed the 1-year visit. After
the 1-year visit, you should have standard of care follow-up visits and/or tests to check the
status of the disease. Your study doctor can discuss this with you in detail. Your
information will still be collected even if you go on to another treatment.

You will be taken off study if the disease comes back after transplant, if intolerable side
effects occur, or if you are unable to follow study directions. If you are unable or
unwilling to have follow-up visits and/or study tests, you may also be taken off study.

You should talk to the study doctor if you want to leave the study early. If you are taken
off study early, you still may need to return for routine follow-up visits after the
transplant, if your doctor thinks it is needed.

It may be life-threatening to leave the study after you have begun to receive the study drug
but before you receive the stem cells.

Study Tests:

As part of your standard care, you will remain in the hospital for about 3-4 weeks after the
transplant. Starting on Day -2 until you are discharged from the hospital, blood (about 2
teaspoons) will be drawn every day to check for side effects, for routine tests, to check
your kidney and liver function, and to check for infections. This may be repeated more
frequently, if your doctor thinks it is needed.

After you are sent home from the hospital, you must remain in the Houston area to be checked
for infections and other transplant-related side effects until about 3 months after
transplant. During this time, you will return to the clinic 2 times each week or more often
if your doctor thinks it is needed. At each visit, you will have a physical exam, and blood
(about 2 teaspoons) will be drawn for routine tests.

About 3 months after the transplant:

- You will have a PET scan to check the status of the disease.

- You will have a bone marrow aspiration and biopsy to check the status of the disease. To
collect a bone marrow aspirate/biopsy, an area of the hip or other site is numbed with
anesthetic, and a small amount of bone marrow and bone is withdrawn through a large
needle.

Every 3 months during the first year after the transplant, blood (about 1-2 tablespoons) will
be drawn and urine will be collected to check your immune response and status of the disease.

About 1 year after the transplant:

- You will have a bone survey (series of x-rays) to check the status of the disease.

- You will have a bone marrow aspiration and biopsy to check the status of the disease.

Pharmacokinetic (PK) Testing:

Blood (about 1-2 teaspoons each time) will be drawn for PK testing at different schedules,
depending on when you are enrolled in this study. PK testing measures the amount of study
drug in the body at different time points. The first 30 participants will have Intense PK
Testing, and the remaining 60 participants will have Sparse PK Testing. The study doctor will
tell you which schedule you will follow:

- If you have Intense PK Testing, blood will be drawn 1 time before and 8 times over 8
hours after your first dose of Evomela. If you receive the drug over 8-9 hours, some of
these draws will take place while you are receiving the drug.

- If you have Sparse PK Testing, blood will be drawn before and 4 times over the 8 hours
after your first dose of Evomela. If you receive the drug over 8-9 hours, some of these
draws will take place while you are receiving the drug.

You will be given a heparin lock line will be placed in your vein to lower the number of
needle sticks needed for these draws. If it is not possible for the PK tests to be performed,
you will be taken off study. The study doctor will discuss this with you.

Inclusion Criteria:

1. Patients with multiple myeloma in complete response (CR), partial remission (PR), very
good partial remission (VGPR), or symptomatic stable disease (no evidence of
progression) including patients with light chain MM detected in the serum by free
light chain assay.

2. Patients with non-secretory multiple myeloma [absence of a monoclonal protein (M
protein) in serum as measured by electrophoresis (SPEP) and immunofixation (SIFE) and
the absence of Bence Jones protein in the urine (UPEP) defined by use of conventional
electrophoresis and immunofixation (UIFE) techniques] but with measurable disease on
imaging studies like MRI, CT scan or PET scan.

3. Patients who have received at least two cycles of initial systemic therapy and are
within 2 to 12 months of the first dose. Mobilization therapy is not considered
initial therapy.

4. Age 18 - 70 years.

5. Karnofsky performance score 70% or higher.

6. Cardiac function: left ventricular ejection fraction at rest > 40% within 3 months of
registration.

7. Hepatic function: bilirubin < 2x the upper limit of normal (except patients with
Gilbert Syndrome in whom bilirubin level of >2x upper normal limit will be allowed)
and ALT and AST < 2.5x the upper limit of normal.

8. Renal function: creatinine clearance of >/= 40 mL/min, estimated or calculated using
the Cockcroft-Gault equation.

9. Pulmonary function: DLCO, FEV1, FVC > 50% of predicted value (corrected for
hemoglobin) within 3 months of registration.

10. All female and male subjects of reproductive potential must consent to the use of
effective contraceptive methods as advised by the study doctor during treatment.

11. Signed informed consent form.

Exclusion Criteria:

1. Patients with uncontrolled bacterial, viral or fungal infections (currently taking
medication and progression of clinical symptoms).

2. Patients seropositive for the human immunodeficiency virus (HIV).

3. Patients with history of myocardial infarction within 6 months prior to enrollment or
has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled
angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence
of acute ischemia or active conduction system abnormalities.

4. Patients participating in an investigational new drug protocol within 14 days before
enrollment.

5. Female patients who are pregnant (positive b-HCG) or breast feeding.

6. Prior hematopoietic cell transplantation allogeneic or autologous (A prior autologous
HCT will be allowed as long as it was part of tandem transplantation).

7. Prior organ transplant requiring immunosuppressive therapy.