Phase I Study to Assess the Safety, Tolerability and Pharmacokinetics of CUDC-907 in Patients With Lymphoma or Multiple Myeloma

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Curis, Inc.
Sponsor:
Collaborator:
The Leukemia and Lymphoma Society
Information provided by (Responsible Party):
Curis, Inc.
ClinicalTrials.gov Identifier:
NCT01742988
First received: December 4, 2012
Last updated: August 12, 2014
Last verified: August 2014

December 4, 2012
August 12, 2014
December 2012
December 2015   (final data collection date for primary outcome measure)
To determine the maximum tolerated dose (MTD) or biologically effective dose (BED) and recommended Phase 2 dose (RP2D) of oral CUDC-907 in patients with relapsed or refractory lymphoma or multiple myeloma [ Time Frame: 21 days (1 cycle of study treatment) ] [ Designated as safety issue: Yes ]
Within any given study arm, the highest dose level studied at which fewer than 2 out of 6 subjects (< 33%) experience a dose limiting toxicity (DLT).
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 [ Time Frame: 21 days (1 cycle of study treatment) ] [ Designated as safety issue: Yes ]
The highest dose level studied at which fewer than 2 out of 6 subjects (< 33%) experience a dose limiting toxicity (DLT).
Complete list of historical versions of study NCT01742988 on ClinicalTrials.gov Archive Site
  • To assess the safety and tolerability of CUDC-907 [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
    Number of participants with adverse events assessed using the NCI Common Terminology Criteria for Adverse Events (CTCAE, v4.0).
  • To assess pharmacokinetics (PK) of oral CUDC-907 [ Time Frame: Pre-dose to ≥24 hours post-dose on the first and fifteenth day of study drug dosing ] [ Designated as safety issue: No ]
    Pharmacokinetic parameters will include area under the concentration-time curve (AUC), maximum plasma concentration (Cmax), half-life (T1/2), clearance (Cl) and volume of distribution (Vd).
  • To evaluate biomarkers of CUDC-907 activity [ Time Frame: Day 1, Day 8, and Day 15 of Cycle 1 dosing. ] [ Designated as safety issue: No ]
    Exploratory biological markers of CUDC-907 activity will be assessed in PBMCs, plasma, skin, hair follicle, tumor and bone marrow samples to explore downstream markers of PI3K and HDAC inhibition and cytokine levels.
  • To assess preliminary anti-cancer activity of CUDC-907 [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    The Investigator will evaluate each subject for response to therapy according to standard response criteria for each individual subject's tumor type (e.g., Revised Response Criteria for Malignant Lymphoma and the International Uniform Response Criteria for Multiple Myeloma).
  • To assess the safety and tolerability of CUDC-907 [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
    Number of participants with adverse events assessed using the NCI Common Terminology Criteria for Adverse Events (CTCAE, v4.0).
  • To assess pharmacokinetics (PK) of oral CUDC-907 [ Time Frame: Pre-dose to 24 hours post-dose on the first and fifteenth day of study drug dosing ] [ Designated as safety issue: No ]
    Pharmacokinetic parameters will include area under the concentration-time curve (AUC), maximum plasma concentration (Cmax), half-life (T1/2), clearance (Cl) and volume of distribution (Vd).
  • To evaluate biomarkers of CUDC-907 activity [ Time Frame: Day 1, Day 8, and Day 15 of Cycle 1 dosing. ] [ Designated as safety issue: No ]

    Pre- and post-dose changes in acetylated histone H3 protein levels in peripheral blood mononuclear cells (PBMCs) on Day 1 and Day 15 of Cycle 1 dosing.

    Pre-dose values in acetylated histone H3 protein levels in PBMCs on Day 8 of Cycle 1 dosing.

  • To assess preliminary anti-cancer activity of CUDC-907 [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    The Investigator will evaluate each subject for response to therapy according to standard response criteria for each individual subject's tumor type (e.g., Revised Response Criteria for Malignant Lymphoma and the International Uniform Response Criteria for Multiple Myeloma).
Not Provided
Not Provided
 
Phase I Study to Assess the Safety, Tolerability and Pharmacokinetics of CUDC-907 in Patients With Lymphoma or Multiple Myeloma
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, dose-escalation study of CUDC-907 in patients with refractory or relapsed lymphoma or multiple myeloma. CUDC-907 is a multi-targeted agent designed to inhibit phosphoinositide 3-kinase (PI3K)and histone deacetylase (HDAC). The study is designed to assess the safety, including the maximum tolerated dose, biologically effective dose, the pharmacokinetics, and the anti-cancer activity of CUDC-907.

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. The following dosing schedules may be examined, all consisting of 21-day cycles and including:

(i) continuous once daily (QD), (ii) twice weekly on Days 1, 4, 8, 11, 15, 18 (BIW) (iii) thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17, 19 (TIW) (iv) four days on/three days off on Days 1-4, 8-11, and 15-18 (4/3), and (v) five days on/two days off on Days 1-5, 8-12, and 15-19 (5/2)

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, and may continue to receive additional treatment until disease progression has been documented or other treatment discontinuation criteria have been met.

MTD or BED expansion cohorts of up to 36 evaluable (e.g., up to 12 subjects in each of 2 or 3 specific tumor types or subtype) to better define the safety, tolerability and preliminary antitumor and pharmacodynamic activity of the study treatment, as well as suitability as an RP2D and schedule.

Safety and tolerability will be assessed by the incidence and severity of adverse events as determined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v4.03). A Safety Review Committee (SRC) comprised of the Medical Monitor, Principal Investigators, and Sponsor representatives, will be convened to review safety information and to decide upon dose escalation and further subject enrollment.

The antitumor activity of study treatment will be assessed according to 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 peripheral blood mononuclear cells (PBMC), plasma and tissue specimens (skin, tumor and bone marrow samples, where available).

Interventional
Phase 1
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Multiple Myeloma
  • Lymphoma
Drug: CUDC-907
CUDC-907 administered orally with meals.
  • Experimental: CUDC-907 - Continuous Once Daily
    30-60 mg/day CUDC-907, orally administered continuous once daily in continuous 21 day cycles until disease progression or other discontinuation criteria are met.
    Intervention: Drug: CUDC-907
  • Experimental: CUDC-907 - 2x/week
    60-240 mg/day CUDC-907, orally administered twice weekly on Days 1, 4, 8, 11, 15, 18 in continuous 21 day cycles until disease progression or other discontinuation criteria are met.
    Intervention: Drug: CUDC-907
  • Experimental: CUDC-907 - 3x/week
    60-180 mg/day CUDC-907, orally administered thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17, 19 in continuous 21 day cycles until disease progression or other discontinuation criteria are met.
    Intervention: Drug: CUDC-907
  • Experimental: CUDC-907 - four days on/three days off
    60-180 mg/day CUDC-907, orally administered four days on/three days off on Days 1-4, 8-11, and 15-18 in continuous 21 day cycles until disease progression or other discontinuation criteria are met.
    Intervention: Drug: CUDC-907
  • Experimental: CUDC-907 - five days on/two days off
    60-180 mg/day CUDC-907, orally administered five days on/two days off on Days 1-5, 8-12, and 15-19 in continuous 21 day cycles until disease progression or other discontinuation criteria are met.
    Intervention: Drug: CUDC-907
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
117
December 2015
December 2015   (final data collection date for primary outcome measure)

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.
  • 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 defined as more than 1 watery stools/day.
  • 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 compliance with the protocol.
  • No second primary malignancy within 2 years of study entry other than adequately treated non-melanoma skin or superficial bladder cancer, curatively treated carcinoma in situ of the cervix or other curatively treated solid tumor deemed by the investigator to be at low risk for recurrence.
  • Known human immunodeficiency virus (HIV) positive, hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection.
Both
18 Years and older
No
United States
 
NCT01742988
CUDC-907-101
No
Curis, Inc.
Curis, Inc.
The Leukemia and Lymphoma Society
Study Director: Jaye L. Viner, MD Curis, Inc.
Curis, Inc.
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP