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A Phase I Study of Arry-520 and Carfilzomib in Patients With Relapsed/Refractory Multiple Myeloma


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Myeloma

Thank you

Trial Information

A Phase I Study of Arry-520 and Carfilzomib in Patients With Relapsed/Refractory Multiple Myeloma


Study Drugs:

Carfilzomib, an investigational drug, is designed to keep cancer cells from repairing
themselves. If the cancer cells cannot repair themselves, this may cause them to die.

ARRY-520, an investigational drug, is designed to prevent cancer cells from reproducing. By
preventing the tumor cells from reproducing, ARRY-520 may slow the spread of the cancer
cells and may cause them to die.

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a study
group based on when you join this study. Up to 4 groups of 3-6 participants will be
enrolled in Group 1A, and up to 14 total participants will be enrolled in Group 1B. There
will be between 1 and 5 groups of 3-6 participants in Group 2A and up to 14 participants in
Group 2B.

Group 1A:

If you are enrolled in Group 1A, the dose of ARRY-520 you receive will depend on when you
joined this study. The first group of participants will receive the lowest dose levels of
ARRY-520 . Each new group will receive a higher dose of ARRY-520 than the group before it,
if no intolerable side effects were seen. This will continue until the highest tolerable
dose of ARRY-520 is found.

Group 1B Expansion:

If you are enrolled in Group 1B, you will receive ARRY-520 at the highest dose that was
tolerated in Group 1A.

Everyone in Group 1A and B will receive the same dose of carfilzomib.

Group 2A:

If you are enrolled in the Group 2A, the dose of carfilzomib you receive will depend on when
you joined this study. The first group of participants will receive the lowest dose levels
of carfilzomib. Each new group will receive a higher dose of carfilzomib than the group
before it, if no intolerable side effects were seen. Sometimes, the new dose level for one
drug will be raised, while the dose level for the other drug will be the same as the dose
given to the earlier group. This will continue until the highest tolerable dose of
carfilzomib is found.

Group 2B Expansion:

If you are enrolled in Group 2B, you will receive carfilzomib at the highest tolerated dose
that was tolerated in Group 2A.

Everyone in Group 2A and B will receive the highest tolerated dose of ARRY-520 that was
found in Group 1. Group 2B patients may receive ARRY-520 either at the highest tolerated
dose from Group 1 or one dose level lower.

Study Drug Administration:

Each study cycle is 28 days.

On Days 1, 2, 8, 9, 15, and 16 of Cycles 1-8, you will receive carfilzomib by vein over
about 10-30 minutes. The study staff will check you for any side effects for at least 1 hour
after receiving carfilzomib.

On Days 1, 2, 15, and 16 of Cycles 1-8, you will receive ARRY-520 by vein over 1 hour.

After 8 cycles, you may continue receiving carfilzomib on Days 1, 2, 15, and 16. If the
doctor thinks it is in your best interest, you may also receive ARRY-520 on Days 1, 2, 15,
and 16.

You will be given dexamethasone by mouth or vein to help prevent side effects. If it is by
vein it will be over 10 minutes. All groups will receive dexamethasone before all
carfilzomib doses in Cycle 1. If you are in Group 2A, you will also receive dexamethasone
before every carfilzomib dose. You may also receive dexamethasone if you develop chills,
rigors, fevers, or shortness of breath when carfilzomib is given.

You may also receive filgrastim under the skin. This will begin on Day 3 or 4 and Day 17 or
18 of every cycle, and continue 1 time each day for 5-7 days.

You will take an anti-viral drug (such as acyclovir, famciclovir, or valacyclovir) while on
this study to help prevent side effects. Your doctor will explain how often you will need to
take this anti-viral drug.

You must be well hydrated while you are taking carfilzomib:

- Starting 2 days before your first dose of carfilzomib, you must drink 6-8 cups (8
ounces each) of water each day.

- If the doctor thinks it is needed, you may need to keep drinking 6-8 cups of water each
day during Cycle 2 and beyond.

- During every Cycle 1 dose, you will also be given fluids by vein for an hour after you
receive the drug.

Study Visits:

At every study visit, you will be asked about side effects you may have had (such as
numbness and/or tingling).

On Day 1 of every cycle:

- You will have a complete physical exam, including measurement of your vital signs,
height, and weight.

- Your performance status will be recorded.

- Blood (about 2 teaspoons) will be drawn for routine tests. The routine blood draw will
also include a pregnancy test if you are able to become pregnant. A urine test may
also be used rather than the blood test to check for pregnancy.

- Blood (about 1 tablespoon) and urine will be collected to check the status of the
disease. This urine will be collected over a 24-hour period. You will be given a
container for urine collection.

On Days 8, 15, and 22 of Cycle 1, blood (about 2 teaspoons) will be drawn for routine tests.

On Day 8 and 15 of Cycles 2 and beyond, blood (about 2 teaspoons) will be drawn for routine
tests.

Every 4 weeks:

- Blood (about 2 teaspoons) will be drawn to check the status of the disease

- Urine will be collected over 24 hours to check the status of the disease.

- If the doctor thinks it is needed, you will have and x-ray of your bones, MRI scan
and/or a bone marrow aspiration and/or biopsy to check the status of the disease.

Length of Study:

You may continue taking the study drugs for as long as the doctor thinks it is in your best
interest. You will no longer be able to take the study drugs if the disease gets worse, if
intolerable side effects occur, or if you are unable to follow study directions.

Your participation on the study will be over once you have completed the end-of-dosing
visit.

End-of-Dosing Visit:

Within 30 days after you stop taking the study drugs, you will have an end-of-dosing visit.
At this visit, the following tests and procedures will be performed:

- You will have a physical exam, including measurement of your weight and vital signs.

- Your performance status will be recorded.

- You will have an ECG.

- Blood (about 1-2 teaspoons) and urine will be collected for routine tests.

- You will be asked about any drugs you may be taking and any side effects or symptoms
(such as numbness and/or tingling) that you may have.

- Blood (about 1 tablespoon) and urine will be collected to check the status of the
disease. This urine will be collected over a 24-hour period. You will be given a
container for urine collection.

- If your doctor thinks it is needed, you will have a bone marrow aspiration and/or
biopsy to check the status of the disease.

This is an investigational study. ARRY-520 is not FDA approved or commercially available.
It is currently being used for research purposes only. Carfilzomib is FDA approved and
commercially available for the treatment of certain types of multiple myeloma. Its use in
this study is investigational.

Up to 76 participants will take part in this study. All will be enrolled at MD Anderson.


Inclusion Criteria:



1. Confirmed relapsed or refractory MM or PCL. Patients should have received at least 1
prior treatment regimen. Prior treatment must have included at least one full cycle
of a proteasome inhibitor (e.g., bortezomib) and at least one full cycle of an IMiD
(e.g., thalidomide, lenalidomide or pomalidomide). Patients who have had prior
ARRY-520 and carfilzomib will be allowed in the dose escalation phase, however prior
ARRY-520 and carfilzomib will be excluded in the dose expansion cohort of Part A.
Part B: Once a MTD has been established in Part A, additional dose escalation will
occur with subsequent dose escalation of Carfilzomib. During the dose escalation of
Part B, pt must have at least 1 line of prior therapy and no limitations on prior
therapy. At the MTD of part B, an additional 14 patients will be enrolled at the MTD.
Patients who had prior clinical benefit/response to ARRY-520 or Carfilzomib with a
stable disease (SD) or better may be eligible for dose expansion of Part B.

2. Continuation of Inclusion Criteria #1: Patients must be refractory or intolerant to
bortezomib therapy.

3. Measurable MM disease, defined as one of the following: A monoclonal immunoglobulin
(Ig) concentration on serum electrophoresis of >/= 0.5 g/dL for an IgG myeloma, >/=
0.1 g/dL for an IgD myeloma or 0.5 g/dL for an IgA myeloma. Measurable urinary light
chain secretion by quantitative analysis of >/= 200 mg/24 hours. Involved serum FLC
level >/= 10 mg/dL, provided the serum free light chain (FLC) ratio is abnormal.
Patients with oligo- or non-secretory disease must have bone marrow involvement with
at least 30% plasmacytosis.

4. Male or female, >/= 18 years of age at time of signing consent.

5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1 or 2.

6. Adequate hematology laboratory values without transfusion support and without
hematological growth factor support within 2 weeks of Screening: Absolute Neutrophil
Count (ANC) >/= 1.5 × 10^9/L. Platelets >/= 75 × 10^9/L. If the bone marrow contains
>/= 50% plasma cells, a platelet count of >/= 50 × 10^9/L is allowed.

7. Adequate liver and renal function: Aspartate aminotransferase (AST)/serum glutamic
oxaloacetic transaminase (SGOT) and/or alanine aminotransferase (ALT)/serum glutamic
pyruvic transaminase (SGPT) 2.0 mg/dL. Serum creatinine least 50 mL/min (using the Cockcroft and Gault method).

8. Female patients who: Are postmenopausal for at least 1 year before the screening
visit, OR Are surgically sterile, OR If they are of childbearing potential, ( those
who are post menopausal for less than 1 year) must have negative serum or urine
pregnancy test and agree to practice 2 effective methods of contraception, at the
same time, from the time of signing the informed consent through 30 days after the
last dose of study drug, or agree to completely abstain from heterosexual
intercourse. Male patients, even if surgically sterilized (i.e., status
postvasectomy), who: Agree to practice effective barrier contraception during the
entire study treatment period and through 30 days after the last dose of study drug,
OR Agree to completely abstain from heterosexual intercourse.

9. Understand and voluntarily signed informed consent.

Exclusion Criteria:

1. Primary amyloidosis.

2. Treatment with an investigational product or device within 21 days of Cycle 1 Day 1.

3. History of allergic reaction/hypersensitivity to any of the study medications, their
analogues or excipients in the various formulations.

4. Cytotoxic therapy or monoclonal antibodies within 21 days prior to Cycle 1 Day 1.

5. Radiotherapy within 21 days prior to Cycle 1 Day 1. However, if the radiation portal
covered of the end date of radiotherapy.

6. Major surgery within 14 days and minor surgery within 7 days prior to Cycle 1 Day 1.

7. Corticosteroid doses > 10 mg/day of prednisone or equivalent within 14 days prior to
Cycle 1 Day 1.

8. Medical, psychiatric, cognitive or other conditions that compromise the patient's
ability to understand the patient information, to give informed consent, to comply
with the study protocol or to complete the study or, in the judgment of the
Investigator, would make the patient inappropriate for study participation.

9. Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize
carfilzomib)

10. Contraindication to any of the required concomitant drugs or supportive treatments,
including hypersensitivity to all anticoagulation and antiplatelet options, antiviral
drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment

11. Patients who are eligible for autologous transplantation

12. New York Heart Association Class III or IV congestive heart failure and other
appropriate cardiac conditions (e.g., history of myocardial infarction,
severe/unstable angina, cardiac dysrhythmias of Grade >/= 2, etc.)

13. Lactating women

14. Patients with known HIV seropositivity

15. Patients with active clinical infections

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose (MTD) of ARRY-520 With Carfilzomib

Outcome Description:

MTD is the level at which ≥2/6 or ≥2/3 dose limiting toxicities (DLTs) are observed in after completion of one cycle (28 days) of combination therapy.

Outcome Time Frame:

Evaluated with each 28 day cycle

Safety Issue:

Yes

Principal Investigator

Jatin J. Shah, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

2011-0144

NCT ID:

NCT01372540

Start Date:

February 2012

Completion Date:

Related Keywords:

  • Myeloma
  • Relapsed/Refractory Multiple Myeloma
  • MM
  • Plasma Cell Leukemia
  • PCL
  • Arry-520
  • Carfilzomib
  • Dexamethasone
  • Decadron
  • Filgrastim
  • G-CSF
  • Neupogen
  • Multiple Myeloma
  • Neoplasms, Plasma Cell

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030