A Phase 1 Study Evaluating CB-5083 in Subjects With Lymphoid Hematological Malignancies



Status:Recruiting
Conditions:Blood Cancer, Blood Cancer, Blood Cancer, Hematology, Hematology
Therapuetic Areas:Hematology, Oncology
Healthy:No
Age Range:18 - Any
Updated:3/25/2017
Start Date:July 2014
Contact:Shanna Stopatschinskaja, MD
Email:sstopatschinskaja@cleavebio.com
Phone:650 443 3037

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A Phase 1, Dose-Escalation/Dose-Expansion Study Evaluating the Safety, Pharmacokinetics and Pharmacodynamic Effects of Orally Administered CB-5083 in Subjects With Lymphoid Hematological Malignancies

The purpose of this study is to determine the safety, tolerability, dose limiting
toxicities, and maximum tolerated dose of CB-5083 in subjects with lymphoid hematological
malignancies.


Inclusion Criteria:

1. Males and females ≥18 years of age at the time of signing the consent form.

2. Dose Escalation Phase: Have a documented diagnosis of a lymphoid hematological
malignancy as described by the 2008 World Health Organization (WHO) classification
that requires therapy and for which there is no standard of care or standard of care
is not expected to be effective. Subjects must not be candidates for anti-tumor
regimens known to provide clinical benefit.

MM Dose Expansion Cohort:

3. Must have a documented diagnosis of relapsed and refractory multiple myeloma defined
by the International Myeloma Working Group (IMWG) criteria.

4. Must have measurable disease defined as:

- Serum M-protein ≥ 0.5g/dL of IgA or ≥ 1 g/dL of IgG, or

- Urine M-protein ≥ 200 mg/24 hr, or

- Involved FLC assay > 10 mg/dL with abnormal FLC ratio.

5. Must have received at least 4 prior therapies, including an alkylating agent (unless
not clinically indicated), proteasome inhibitor, an immunomodulatory (IMiD) and CD38
targeted therapy. At least 3 prior therapies where CD38 targeted therapies are not
approved, not commercially accessible, contraindicated or refused by subject.

DLBCL Dose Expansion Arm:

6. Must have histologically confirmed DLBCL that is relapsed or refractory to previous
therapy.

7. Must have ≥1 measurable disease sites as defined by standard Lugano classification.

8. Must have received at least 2 prior therapies, including a CD20 targeted therapy,
alkylating agent or corticosteroid; subjects who are not eligible for high-dose
chemotherapy and autologous stem cell transplantation (HD-ASCT) are eligible with
exposure to at least 1 prior therapy.

Waldstrom's Macroglobulinemia Dose Expansion Arm:

9. Must have a confirmed diagnosis of WM as defined by the Second International
Workshop, with a clinical indication for treatment.

10. Must have measurable disease, defined as presence of serum immunoglobulin M (IgM)
with a minimum IgM level of ≥ 2 times the upper limit of each institution's normal
value is required.

11. Must have relapsed/refractory disease after receiving 1 or more lines of therapy,
including a Bruton tyrosine kinase (BTK) inhibitor (eg ibrutinib) if approved by the
local health authority and commercially accessible.

All Arms:

12. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤2.

13. Adequate bone marrow function without transfusion or growth factor support, defined
as:

- Absolute neutrophil count ≥ 1,000/μL;

- Platelet count ≥ 50,000/μL;

- Hemoglobin ≥ 8.0 g/dL

14. Adequate organ function defined as:

- Serum creatinine ≤ 1.5 mg/dL or creatinine clearance > 45 mL/min according to
Cockcroft‑Gault formula; (If creatinine clearance calculated from a 24-hour
urine sample is ≥45 mL/min, the subject will qualify for the study).

- Serum total bilirubin ≤ 2.0 mg/dL (34.2 μmol/L); or > 3.0 × upper limit of
normal (ULN) for subjects with hereditary benign hyperbilirubinemia

- AST (SGOT) ≤ 3 × the ULN;

- ALT (SGPT) ≤ 3 × the ULN;

15. Subjects who are fertile agree to use an effective barrier method of birth control
(ie, latex condom, diaphragm, cervical cap, etc) to avoid pregnancy. Female subjects
need a negative serum or urine pregnancy test within 7 days of study enrollment
(applies only if subject is of childbearing potential. Non‑childbearing is defined as
≥ 1 year postmenopausal or surgically sterilized).

16. Willing and able to provide written Informed Consent and adhere to study procedures.

Exclusion Criteria:

1. Subjects with leukemia are excluded, with the exception of chronic lymphocytic
leukemia (CLL), who are allowed in the dose escalation phase. Subjects with Burkitt
lymphoma, plasma cell leukemia, POEMS syndrome (polyneuropathy, organomegaly,
endocrinopathy, monoclonal gammopathy, and skin changes), or amyloidosis are also
excluded.

2. Clinically active central nervous system (CNS) cancer involvement. Imaging to exclude
CNS involvement not required.

3. Previous or concomitant malignancy, except for basal-cell or squamous cell carcinoma
of the skin or carcinoma-in-situ of the uterine cervix. Subjects with other
malignancies are eligible if they have remained disease free for at least 2 years
prior to study entry;

4. Use of any anti-cancer drug therapy within 14 days prior to Baseline (within 28 days
for monoclonal antibodies [eg anti-CD38]).

5. Use of any investigational agent within 28 days prior to Baseline.

6. Presence of clinically significant non-hematological toxicity of prior chemotherapy
that has not resolved to ≤ Grade 1 as determined by CTCAE v 4.0, with the exception
of alopecia and peripheral neuropathy. Note: Peripheral neuropathy > Grade 2 plus
pain, or Grade 3 or Grade 4 are excluded.

7. Radiotherapy within 14 days prior to Baseline.

8. Major surgery within 6 weeks prior to Baseline. The subject must have recovered from
surgery and be without current complications of infection or dehiscence.

9. Peripheral autologous stem cell transplant within 12 weeks prior to Baseline; prior
allogeneic transplants within 16 weeks or chronic use of immunosuppressants.

10. Active infection requiring systemic therapy, including known human immunodeficiency
virus (HIV), acquired immunodeficiency syndrome-related illness, or active hepatitis
B virus (HBV) or hepatitis C virus (HCV) infection.

11. Major cardiac abnormalities as defined but not limited to the following: uncontrolled
angina or unstable life-threatening arrhythmias, history of myocardial infarction
within 12 weeks prior to Baseline, Class 3 or higher New York Heart Association
(NYHA) congestive heart failure, or severe cardiac insufficiency, persistent (3
consecutive electrocardiograms (ECGs) performed ≥ 5 minutes apart) prolongation of
the QTc (Fridericia) interval to > 480 msec.

12. Cerebrovascular accident, coronary/peripheral artery bypass graft surgery, transient
ischemic attack, or pulmonary embolism within 12 weeks prior to Baseline.

13. Major gastrointestinal (GI) disease as defined but not limited to the following:
history of inflammatory bowel disease or other illness resulting in chronic diarrhea,
known achlorhydria or history of GI surgery that could reduce the acidity of the
stomach, acute pancreatitis or cholecystitis within 6 months prior to Baseline, or GI
disease that may interfere with the absorption of orally-administered drugs.

14. Grade 3 or 4 eye disorder at study entry, unless stable and longstanding (>3 months)
and unlikely to interfere with protocol-required ophthalmology assessments.

15. A condition that is expected to require concomitant use of any medication listed as
prohibited while on study.

16. Is a pregnant or lactating female.

17. Has any severe, acute, or chronic medical or psychiatric condition, or laboratory
abnormality that may increase the risk associated with study participation or study
drug administration, may interfere with the informed consent process and/or with
compliance with the requirements of the study, or may interfere with the
interpretation of the study results and, in the Investigator's opinion, would make
the subject inappropriate for entry into this study.
We found this trial at
7
sites
Toronto, Ontario
Principal Investigator: Donna Reece, MD
Phone: 416-946-4501
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201 Dowman Dr
Atlanta, Georgia 30303
(404) 727-6123
Principal Investigator: Ajay K Nooka, MD
Emory University Emory University, recognized internationally for its outstanding liberal artscolleges, graduate and professional schools,...
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1 Brookings Drive
St. Louis, Missouri 63110
 (314) 935-5000
Principal Investigator: Ravi Vij, MD
Phone: 314-747-7813
Washington University Washington University creates an environment to encourage and support an ethos of wide-ranging...
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Bethesda, Maryland 20817
Principal Investigator: Ralph V Boccia, MD
Phone: 310-571-2016
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1500 East Duarte Road
Duarte, California 91010
626-256-HOPE (4673)
City of Hope National Medical Center City of Hope is dedicated to making a difference...
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30 Prospect Ave
Hackensack, New Jersey 07601
(201) 996-2000
Principal Investigator: David Siegel, MD
Phone: 551-996-8704
Hackensack University Medical Center Hackensack University Medical Center, part of the Hackensack University Health Network,...
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San Francisco, California 94143
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