Phase I Open Label, Multi-center, Dose-escalation Study to Assess the Safety, Tolerability and Pharmacokinetics of Orally Administered CUDC-907, a PI3K and HDAC Inhibitor, in Subjects With Refractory or Relapsed Lymphoma or Multiple Myeloma
18 Years
N/A
Both
Multiple Myeloma, Lymphoma
Trial Information
Phase I Open Label, Multi-center, Dose-escalation Study to Assess the Safety, Tolerability and Pharmacokinetics of Orally Administered CUDC-907, a PI3K and HDAC Inhibitor, in Subjects With Refractory or Relapsed Lymphoma or Multiple Myeloma
This is a Phase I, open-label, multi-center dose-escalation trial evaluating the safety and
tolerability of CUDC-907 as a single agent administered orally, once daily, to patients with
relapsed or refractory lymphoma or multiple myeloma.
Sequential dose escalation cohorts of oral CUDC-907 are planned. Subject enrollment and
dose escalation will proceed according to a standard 3+3 design. In the absence of DLT,
each subject will be treated for a minimum of 21 days of continuous daily dosing, and may
continue to receive additional treatment until disease progression has been documented or
other treatment discontinuation criteria have been met. No intrasubject dose escalation will
be allowed. An MTD expansion cohort of up to 12 evaluable subjects may also be enrolled in
order to better define the safety, tolerability and activity of the study treatment.
Safety and tolerability will be assessed by the incidence and severity of adverse events as
determined by NCI Common Terminology Criteria for Adverse Events (CTCAE v4.03).
The antitumor activity of study treatment will be assessed according standard response
criteria as appropriate for each individual subject's tumor type (e.g., Revised Response
Criteria for Malignant Lymphoma and the International Uniform Response Criteria for Multiple
Myeloma).
Exploratory biological markers of activity will be assessed in PBMC and plasma.
Inclusion Criteria:
- Subjects of ≥ 18 years of age with histopathologically confirmed diagnosis of
lymphoma or multiple myeloma that is refractory to or relapsed after at least 2 prior
regimens.
- Measurable or evaluable disease.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
- Recovery to Grade 1 or baseline of any toxicity due to prior systemic treatments
(excluding alopecia).
- Absolute neutrophil count ≥ 1,000/µL; platelets ≥ 75,000/µL; creatinine ≤ 1.5x upper
limit of normal (ULN); total bilirubin ≤ 1.5x ULN; AST/ALT ≤ 2.5x ULN. For subjects
with documented liver metastases, the AST/ALT may be ≤ 5x ULN.
- Life expectancy of at least 3 months.
- Women of child bearing potential must have a negative serum pregnancy test.
- Men and women of child bearing potential must agree to use adequate birth control
throughout their participation in the study and for 30 days following the last study
treatment.
- Able to provide written informed consent and to follow protocol requirements.
Exclusion Criteria:
- Systemic anticancer therapy within 3 weeks of study entry, except for nitrosoureas or
mitomycin C (6 weeks).
- Graft vs. host disease following prior allogeneic transplant within 3 months prior to
study treatment.
- Other investigational agents within 21 days prior to study treatment.
- Prior treatment with a PI3K inhibitor.
- Peripheral neuropathy of Grade 2 or higher within 14 days prior to study treatment.
- Pregnant or lactating/breast-feeding women.
- Ongoing treatment with chronic immunosuppressants.
- Active CNS lymphoma.
- Known gastrointestinal condition that would interfere with swallowing or the oral
absorption or tolerance of CUDC-907.
- Ongoing diarrhea of any grade (per NCI CTCAE v4.03).
- Serious infection requiring systemic antibiotic therapy within 14 days prior to study
treatment.
- Uncontrolled or severe cardiovascular disease, including myocardial infarct or
unstable angina within 6 months prior to study treatment, New York Heart Association
(NYHA) Class II or greater congestive heart failure, serious arrhythmias requiring
medication for treatment, clinically significant pericardial disease, or cardiac
amyloidosis.
- Unstable or clinically significant concurrent medical condition that would, in the
opinion of the investigator, jeopardize the safety of a subject and/or their
compliance with the protocol.
- Prior malignancy within 2 years except non-melanoma skin cancer
- Known human immunodeficiency virus (HIV) positive, hepatitis B surface
antigen-positive status, or known or suspected active hepatitis C infection.
Type of Study:
Interventional
Study Design:
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
To determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of oral CUDC-907 in patients with relapsed or refractory lymphoma or multiple myeloma
Outcome Description:
The highest dose level studied at which fewer than 2 out of 6 subjects (< 33%) experience a dose limiting toxicity (DLT).
Outcome Time Frame:
21 days (1 cycle of study treatment)
Safety Issue:
Yes
Principal Investigator
Maurizio Voi, MD
Investigator Role:
Study Director
Investigator Affiliation:
Curis, Inc.
Authority:
United States: Food and Drug Administration
Study ID:
CUDC-907-101
NCT ID:
NCT01742988
Start Date:
December 2012
Completion Date:
April 2014
Related Keywords:
- Multiple Myeloma
- Lymphoma
- PI3K
- HDAC
- Open-Label
- Dose-Escalation
- Lymphoma
- Multiple Myeloma
- Neoplasms, Plasma Cell
Name | Location |
|---|---|
| MD Anderson Cancer Center | Houston, Texas 77030-4096 |
| Memorial Sloan-Kettering Cancer Center | New York, New York 10021 |
| Sarah Cannon Research Institute | Nashville, Tennessee 37203 |
