Safety and Efficacy Study of CC-486 in Subjects With Myelodysplastic Syndromes



Status:Active, not recruiting
Conditions:Blood Cancer, Blood Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - Any
Updated:12/20/2018
Start Date:July 6, 2015
End Date:June 18, 2019

Use our guide to learn which trials are right for you!

A Phase 2, International, Multicenter, Randomized, Open-label, Parallel Group to Evaluate the Efficacy and Safety of Cc-486 (Oral Azacitidine) Alone in Combination With Durvalumab (MEDI4736) in Subjects With Myelodysplastic Syndromes Who Fail to Achieve an Objective Response to Treatment With Azacitidine for Injection or Decitabine

Evaluate the safety and efficacy of CC-486 in Subjects with Myelodysplastic Syndromes who
failed to achieve an objective response post iHMA treatment

Reason for removing the Combo arm: Due to difficulties with dose-finding, the durvalumab plus
CC-486 combination arm is closed to enrollment


Inclusion Criteria:

1. Male or female, ≥ 18 years of age at the time of signing the informed consent document

2. Documented diagnosis of MDS (MYELODYSPLASTIC SYNDROMES), classified according to FAB
(FRENCH-AMERICAN BRITISH) classification criteria

3. Adequate course of treatment with an injectable hypomethylating agent (azacitidine for
injection or decitabine) as the last therapeutic intervention for MDS (MYELODYSPLASTIC
SYNDROMES) prior to beginning screening for this study. Adequate is defined as:

- having received at least 6 consecutive 4-week treatment cycles with azacitidine for
injection, or

- having received at least 4 consecutive 6-week treatment cycles with decitabine
(3-day regimen) or at least 6 consecutive 4-week treatment cycles with decitabine
(5-day regimen), or

- having demonstrated inability to tolerate treatment with an injectable
hypomethylating agent because of unacceptable drug-related toxicity after at least 3
months of attempted treatment: Three 28-day cycles of azacitidine for injection or
decitabine 5-day regimen; two 42-day cycles of decitabine 3-day regimen.

4. Documented disease progression or stable disease as best response to treatment (or
attempted treatment) with azacitidine for injection or decitabine. Those achieving an
objective response to treatment regimen with an injectable Hypomethylating agent (HMA)
are excluded from participation in this study.

Definitions of disease progression are modified from IWG (INTERNATIONAL WORKING GROUP)
2006 criteria and include:

- Pre-injectable HMA (HYPOMETHYLATING AGENT) baseline bone marrow myeloblasts:

a. Less than 5%: ≥ 100% increase to ≥ 8% blasts b. ≥ 5%: ≥ 50% increase to ≥ 10%
blasts Note: ≥ 30% blasts is considered AML (ACUTE MYELOID LEUKEMIAT) per FAB
(FRENCH-AMERICAN BRITISH)classification. Subjects known to have ≥ 30% blasts are not
eligible for inclusion in this study. RECOG (Eastern Cooperative Oncology Group)
nizing limitations of blast cell quantification, this protocol will allow subjects
with pre-enrollment bone marrow blast counts up to 33% on the screening bone marrow
examination to be considered for inclusion. Assessment may be made according to local
bone marrow examination to facilitate enrollment of eligible subjects into the
treatment phase of the study.

- Any clinical worsening from pre-injectable HMA (HYPOMETHYLATING AGENT) baseline
condition, including:

1. sustained clinically-significant worsening (investigator's assessment) from
baseline granulocyte, platelet, or hemoglobin values (≥ 2 values, separated by ≥
2 weeks)

- worsening granulocytes should be ≥ 50% decrease from pre-injectable HMA
(HYPOMETHYLATING AGENT) baseline value

- worsening platelets should be ≥ 50% decrease from pre-injectable HMA
(HYPOMETHYLATING AGENT) baseline value (untransfused)

- worsening hemoglobin should be ≥ 1.5 g/dL decrease from preinjectable HMA
(HYPOMETHYLATING AGENT) baseline value in subjects not receiving RBC (RED
BLOOD CELL) transfusions

2. meaningful worsening in RBC (RED BLOOD CELL) or platelet transfusion requirement

Definition of stable disease is based on modified IWG (INTERNATIONAL WORKING GROUP)
2006 criteria:

- Failure to achieve any objective response (CR - complete remission, PR - partial
remissino, mCR - marrow complete remission, or HI - hematologic improvement), but no
evidence of disease progression within the 8 weeks leading to the subject's first dose
of IP (INVESTIGATIONAL PRODUCT) in this study (Cycle 1, Day 1)

5. Have the last dose of the prior treatment regimen (injectable HMA (HYPOMETHYLATING
AGENT) - azacitidine for injection or decitabine) not more than 16 weeks prior to
screening for this study (date of informed consent signature).

6. No less than 3 weeks between the last dose of the prior treatment regimen (injectable
HMA (HYPOMETHYLATING AGENT) - azacitidine for injection or decitabine) and the planned
date of first dose of IP (IINVESTIGATIONAL PRODUCT).

7. Have an ECOG (EASTERN COOPERATIVE ONCOLOGY GROUP) performance status of 0, 1, or 2

8. Females subjects of childbearing potential (FCBP)1 may participate, providing they
meet the following conditions:

1. Have two negative pregnancy tests as verified by the investigator prior to
starting any IP therapy: serum pregnancy test at screening and negative serum or
urine pregnancy test (investigator's discretion) within 72 hours prior to
starting treatment with IP (Cycle 1, Day 1). They must agree to ongoing pregnancy
testing during the course of the study (before beginning each subsequent cycle of
treatment), and after the last dose of any IP. This applies even if the subject
practices complete abstinence2 from heterosexual contact.

2. Agree to practice true abstinence2 (which must be reviewed on a monthly basis and
source documented) or agree to the use of highly effective methods of
contraception from 28 days prior to starting azacitidine, and must agree to
continue using such precautions while taking azacitidine (including dose
interruptions) and for up to 90 days after the last dose of azacitidine.
Cessation of contraception after this point should be discussed with a
responsible physician

3. Agree to abstain from breastfeeding during study participation and for at least
90 days after the last dose of IP.

Note that the screening serum pregnancy test can also be used as the test prior to starting
IP (Investigational Product) if it is performed within the 72-hour timeframe.

9. Male subjects must:

1. Male subjects must:

1. Either practice true abstinence2 from heterosexual contact (which must be
reviewed on a monthly basis) or agree to avoid fathering a child, to use highly
effective methods of contraception, male condom plus spermicide during sexual
contact with a pregnant female or a female of child bearing potential (even if he
has undergone a successful vasectomy) from starting dose of IP (Cycle 1 Day 1),
including dose interruptions through 90 days after receipt of the last dose of
azacitidine.

2. Refrain from semen or sperm donation while taking IP and for at least 90 days after
the last dose of IP.

10. Understand and voluntarily sign an informed consent document prior to any
study-related assessments or procedures conducted.

11. Be able to adhere to the study visit schedule and other protocol requirements.

12. Understand and voluntarily sign a biomarker-specific component of the informed
consent document prior to any study-related procedures conducted.

Exclusion Criteria:

1. Rapidly-progressing MDS (MYELODYSPLASTIC SYNDROMES), defined as:

1. Known clinically-significant doubling in marrow or perIP (INVESTIGATIONAL
PRODUCT) heral blood blast percentage (to ≥ 20%) in the 8-week period leading to
the first dose of IP (INVESTIGATIONAL PRODUCT) (Cycle 1, Day 1)

2. ≥100% increase in WBC count (myeloid cell line and monocyte series) within the
8-week period leading to Cycle 1, Day 1

2. Acute myelogenous leukemia (AML (ACUTE MYELOID LEUKEMIA) - FAB
(FRENCH-AMERICAN-BRITISH) classification: ≥ 30% blasts in bone marrow). Subjects known
to have ≥ 30% blasts are not eligible for inclusion in this study. Recognizing
limitations of blast cell quantification, this protocol will allow subjects with
pre-enrollment (screening/baseline) bone marrow blast counts up to 33% to be
considered for inclusion.

3. Prior allogeneic stem cell transplant

4. Prior exposure to the investigational oral formulation of decitabine, or other oral
azacitidine derivative at any time in the subject's prior history

5. Prior or ongoing response (IWG 2006: HI, PR, CR, or marrow CR) to treatment with
azacitidine for injection or decitabine, at any time in the subject's prior history,
which includes relapsed disease

6. Ongoing medically significant adverse events from previous treatment, regardless of
the time period

7. Use of any of the following within 28 days prior to the first dose of IP
(INVESTIGATIONAL PRODUCT):

1. thrombopoiesis-stimulating agents ([TSAs]; eg, Romiplostim, Eltrombopag,
Interleukin-11)

2. ESAs (Erythropoiesis stimulating agent) and other RBC (Red blood cell)
hematopoietic growth factors (eg, interleukin-3)

3. hydroxyurea

8. Concurrent use of corticosteroids unless the subject is on a stable or decreasing dose
for ≥ 1 week prior to enrollment for medical conditions other than MDS
(MYELODYSPLASTIC SYNDROMES)

9. History of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis),
celiac disease (ie, sprue), prior gastrectomy or upper bowel removal, or any other
gastrointestinal disorder or defect that would interfere with the absorption,
distribution, metabolism or excretion of the IP (INVESTIGATIONAL PRODUCT) and/or
predispose the subject to an increased risk of gastrointestinal toxicity

10. Prior history of malignancies, other than MDS (MYELODYSPLASTIC SYNDROMES), unless the
subject has been free of the disease for ≥ 3 years. However, subjects with the
following history/concurrent conditions are allowed:

1. Basal or squamous cell carcinoma of the skin

2. Carcinoma in situ of the cervix

3. Carcinoma in situ of the breast

4. Incidental histologic finding of prostate cancer (T1a or T1b using the tumor,
nodes, metastasis [TNM] clinical staging system)

11. Significant active cardiac disease within the previous 6 months, including:

1. New York Heart Association (NYHA) class IV congestive heart failure;

2. Unstable angina or angina requiring surgical or medical intervention; and/or

3. Myocardial infarction

12. Uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing
signs/symptoms related to the infection without improvement despite appropriate
antibiotics, antiviral therapy, and/or other treatment)

13. Known Human Immunodeficiency Virus (HIV) or Hepatitis C (HCV) infection, or evidence
of active Hepatitis B Virus (HBV) infection

14. Any of the following laboratory abnormalities:

1. Serum AST/SGOT (Aspartate transaminase / Serum glutamic oxaloacetic transaminase)
or ALT/SGPT (Alanine aminotransaminase / Serum glutamic pyruvate transaminase) >
2.5 x ULN (upper limit of normal)

2. Serum total bilirubin > 1.5 x ULN (upper limit of normal). Higher levels are
acceptable if these can be attributed to active red blood cell precursor
destruction within the bone marrow (ie, ineffective erythropoiesis). Subjects are
excluded if there is evidence of autoimmune hemolytic anemia manifested as a
corrected reticulocyte count of > 2% with either a positive Coombs' test or over
50% of indirect bilirubin

3. Serum creatinine > 2.5 x ULN (upper limit of normal)

4. Absolute WBC (white blood cell) count ≥ 20 x 109/L

15. Known or suspected hypersensitivity to azacitidine, mannitol, its constituents, or to
any other humanized monoclonal antibody

16. Pregnant, planning to become pregnant starting from 28 days prior to receiving CC-486
throughout your participation in the study, and for at least 90 days following your
last dose of study treatment, or breast-feeding females

17. Any significant medical condition, laboratory abnormality, or psychiatric illness that
would prevent the subject from participating in the study

18. Any condition including the presence of laboratory abnormalities, which places the
subject at unacceptable risk if he/she were to participate in the study

19. Any condition that confounds the ability to interpret data from the study, including
known or suspected conditions other than MDS (MYELODYSPLASTIC SYNDROMES), associated
with anemia

20. Having received any prior MAb (monoclonal antibodies) against CTLA-4 (cytotoxic T
lymphocyte-associated antigen), PD-1, or PD-L1 or having received other
investigational MAbs (monoclonalantibodies) within 6 months

21. Clinical evidence of central nervous system (CNS) or pulmonary leukostasis, or CNS
leukemia

22. Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [eg, colitis, Crohn's disease], diverticulitis with the
exception of a prior episode that has resolved or diverticulosis, celiac disease,
irritable bowel disease, or other serious gastrointestinal chronic conditions
associated with diarrhea; systemic lupus erythematosus; Wegener's syndrome
[granulomatosis with polyangiitis]; myasthenia gravis; Graves' disease; rheumatoid
arthritis; hypophysitis, uveitis; etc) within the past 3 years prior to the start of
treatment. The following are exceptions to this criterion:

1. Subjects with vitiligo or alopecia;

2. Subjects with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone
replacement for ≥ 3 months; or

3. Subjects with psoriasis not requiring systemic treatment

23. History of primary immunodeficiency

24. Active myeloproliferative neoplasms (MPN) and chronic myelomonocytic leukemia (CMML)
We found this trial at
15
sites
1 Ingalls Dr
Harvey, Illinois 60426
(708) 333-2300
Ingalls Memorial Hospital As the area's only independent not-for-profit healthcare system, Ingalls has the ability...
?
mi
from
Harvey, IL
Click here to add this to my saved trials
1601 Northwest 12th Avenue
Miami, Florida 33136
(305) 243-6545
University of Miami Miller School of Medicine The University of Miami Leonard M. Miller School...
?
mi
from
Miami, FL
Click here to add this to my saved trials
12902 USF Magnolia Dr
Tampa, Florida 33612
(888) 663-3488
H. Lee Moffitt Cancer Center & Research Institute Moffitt Cancer Center in Tampa, Florida, has...
?
mi
from
Tampa, FL
Click here to add this to my saved trials
Chicago, Illinois 60637
?
mi
from
Chicago, IL
Click here to add this to my saved trials
92 2nd St
Hackensack, New Jersey 07601
(201) 996-5900
John Theurer Cancer Center at the Hackensack University Medical Center The mission of the John...
?
mi
from
Hackensack, NJ
Click here to add this to my saved trials
Houston, Texas 77030
?
mi
from
Houston, TX
Click here to add this to my saved trials
200 Hawkins Dr,
Iowa City, Iowa 52242
866-452-8507
University of Iowa Hospitals and Clinics University of Iowa Hospitals and Clinics—recognized as one of...
?
mi
from
Iowa City, IA
Click here to add this to my saved trials
529 S Jackson St
Louisville, Kentucky 40202
(502) 562-4369
James Graham Brown Cancer Center No one should feel compelled to leave Kentucky to seek...
?
mi
from
Louisville, KY
Click here to add this to my saved trials
8701 W Watertown Plank Rd
Milwaukee, Wisconsin
(414) 955-8296
Medical College of Wisconsin The Medical College (MCW) of Wisconsin is a major national research...
?
mi
from
Milwaukee, WI
Click here to add this to my saved trials
New Haven, Connecticut 6520
(203) 432-4771
Yale University Yale's roots can be traced back to the 1640s, when colonial clergymen led...
?
mi
from
New Haven, CT
Click here to add this to my saved trials
1428 Madison Ave
New York, New York 10029
(212) 241-6500
Icahn School of Medicine at Mount Sinai Icahn School of Medicine at Mount Sinai is...
?
mi
from
New York, NY
Click here to add this to my saved trials
3451 Walnut St
Philadelphia, Pennsylvania 19104
1 (215) 898-5000
Univ of Pennsylvania Penn has a long and proud tradition of intellectual rigor and pursuit...
?
mi
from
Philadelphia, PA
Click here to add this to my saved trials
Pittsburgh, Pennsylvania 15232
?
mi
from
Pittsburgh, PA
Click here to add this to my saved trials
San Antonio, Texas 78229
?
mi
from
San Antonio, TX
Click here to add this to my saved trials
Westmead, New South Wales 2145
?
mi
from
Westmead,
Click here to add this to my saved trials