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Phase 1/2A Dose Escalation Study in CLL, SLL or NHL

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ClinicalTrials.gov Identifier: NCT01994382
Recruitment Status : Active, not recruiting
First Posted : November 25, 2013
Last Update Posted : October 6, 2020
Sponsor:
Information provided by (Responsible Party):
Portola Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE November 8, 2013
First Posted Date  ICMJE November 25, 2013
Last Update Posted Date October 6, 2020
Study Start Date  ICMJE August 2013
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 20, 2017)
Maximum tolerated dose (MTD) of cerdulatinib in patients with relapsed/refractory CLL/SLL or B-cell NHL. [ Time Frame: 28-day cycles until end of treatment ]
Original Primary Outcome Measures  ICMJE
 (submitted: November 19, 2013)
Maximum tolerated dose (MTD) of PRT062070 in patients with relapsed/refractory CLL, SLL or B-cell NHL. [ Time Frame: Approximately 84 days (baseline to end of treatment) ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 20, 2017)
  • Frequency and severity of dose limiting toxicity as classified by Common Terminology Criteria for Adverse Events (CTCAEv4) by dose level. (Phase 1) [ Time Frame: 28-day cycles until end of treatment ]
    Assessments: Antitumor activity of cerdulatinib as measured by ORR defined as CR+PR as measured by CT and CT/PET
  • Assess antitumor activity of B-cell, T-cell NHL, or CLL/SLL, as a single agent and with rituximab for B-cell NHL (subtypes B-cell, T-cell NHL, or CLL/SLL) as single agent and with rituximab for B-cell NHL. [ Time Frame: 28-day cycles until end of treatment ]
    Assessments: Duration of response DOR, progression free survival PFS, time to treatment response TTR and lymph node response LNR, clinical benefit rate (CR+PR+SD)
  • To further evaluate the PK profile of cerdulatinib in patients with specific subtypes of B-cell or T-cell NHL, alone or in combination with rituximab for B-cell NHL. [ Time Frame: 28-day cycles until end of treatment ]
    Assessments: (Cmax) and area under the plasma concentration versus time curve (AUC) of PRT602070.
  • To further evaluate the PD of cerdulatinib in patients with specific subtypes of B-cell or T-cell NHL, alone or in combination with rituximab for B-cell NHL. [ Time Frame: 28-day cycles until end of treatment ]
  • To assess tumor phenotype and genotype in relation to clinical response [ Time Frame: 28-day cycles until end of treatment ]
  • To further evaluate the safety and tolerability of cerdulatinib in patients with specific subtypes of B-cell, T-cell NHL or CLL/SLL and the combination of cerdulatinib with rituximab in patients wtih B-cell NHL [ Time Frame: 28-day cycles until end of treatment ]
    Assessments: PE, vitals, laboratory values and AEs
  • To evaluate the relationship between markers of inflammation with clinical outcome and overall health as determined by the Global Health Assessment. [ Time Frame: 28-day cycles until end of treatment ]
  • To assess Minimal Residual Disease (MRD) status in CLL patients achieving a complete response/ complete response incomplete blood count recovery/partial response (CR/CRi/PR) by flow cytometry. [ Time Frame: 28-day cycles until end of treatment ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 19, 2013)
  • Frequency and severity of dose limiting toxicity (as classified by Common Terminology Criteria for Adverse Events (CTCAEv4) by dose level. [ Time Frame: Approximately 114 days (baseline to 30 days post last treatment) ]
  • Peak plasma concentration (Cmax) and area under the plasma concentration versus time curve (AUC) of PRT602070. [ Time Frame: Baseline to day 22 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 1/2A Dose Escalation Study in CLL, SLL or NHL
Official Title  ICMJE A Phase 1/2A Open-Label, Multi-Dose, Multi-Center Escalation and Exploratory Study of Cerdulatinib (PRT062070) in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) or B Cell or T Cell Non-Hodgkin Lymphoma (NHL)
Brief Summary This study will identify the highest dose, and assess the safety, of cerdulatinib (PRT062070) that may be given in patients with relapsed/refractory chronic lymphocytic leukemia or non-hodgkin lymphoma
Detailed Description

This is an open-label, Phase 1/2a, multi dose, multi-center trial of orally administered cerdulatinib assessing safety, tolerability and PK parameters conducted in 2 phases:

  • Phase 1: Dose-escalation portion, during which 43 patients enrolled to receive a single-agent cerdulatinib at their assigned dose level starting at 15 mg QD, administered in increasing doses until the MTD/MAD is identified.
  • Phase 2a: Consisting of 6 planned cohorts of up to 40 patients each by cancer type. Five cohorts will receive single agent cerdulatinib at a starting dose of 30 mg BID for 28-day cycles. Cohort 2 receives cerdulatinib plus rituximab IV at 375 mg/m2.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Follicular Lymphoma (FL/Indolent NHL)
  • Aggressive NHL (a NHL)
  • Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL)
  • T-cell Lymphoma (PTCL and CTCL)
  • B-cell Non Hodgkin Lymphoma (NHL)
Intervention  ICMJE Drug: Cerdulatinib (PRT062070)
Study Arms  ICMJE Experimental: cerdulatinib (PRT062070)
Intervention: Drug: cerdulatinib (PRT062070) or cerdulatinib (PRT062070) plus rituximab
Intervention: Drug: Cerdulatinib (PRT062070)
Publications * Coffey GP, Feng J, Betz A, Pandey A, Birrell M, Leeds JM, Der K, Kadri S, Lu P, Segal J, Wang YL, Michelson G, Curnutte JT, Conley PB. Cerdulatinib Pharmacodynamics and Relationships to Tumor Response Following Oral Dosing in Patients with Relapsed/Refractory B-cell Malignancies. Clin Cancer Res. 2019 Feb 15;25(4):1174-1184. doi: 10.1158/1078-0432.CCR-18-1047. Epub 2018 Oct 17.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: June 26, 2020)
220
Original Estimated Enrollment  ICMJE
 (submitted: November 19, 2013)
28
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Phase 1 Specific Patient at least 18yrs of age with histologically confirmed CLL/SLL or B-cell Non-Hodgkin lymphoma (DLBCL, FL, MCL, MZL, lymphoplasmacytic lymphoma).

Phase 2a Inclusion

  • Histological evidence: FL Grade 1-3A/iNHL, with relapsed or refractory disease (iNHL includes LPL/WM, MZL); aNHL, defined as DLBCL, FL Grade 3B, MCL, and transformed NHL with relapsed disease; CLL/SLL, PTCL, or CTCL (with MF/SS) with relapsed or refractory.
  • Received BCR and/or BCL2 inhibitors were intolerant or had relapsed/refractory disease afterwards.
  • Prior treatment for lymphoid malignancy for progressive /refractory disease
  • ≥ 1 prior regimen (min 2 cycles) with antibody conjugate, cytotoxic chemotherapy, or TKI alone or in combination.
  • Measureable disease defined as: ≥ 1 lesion ≥ 1.5 cm single dimension via CT, CT/PET with nodal or mass lesions; Quantifiable circulating tumor cells; or for Waldenström's macroglobulinemia presence of IgM l > 2X ULN; For CTCL: mSWAT > 0
  • Ability to provide diagnostic reports

General Inclusion

  • ECOG Score of 0 or 1.
  • Hematologic ANC > 1000/uL and platelet > 75,000/uL,
  • Serum creatinine of < 1.5 ULN or calculated CrCl of > 50 mL/min
  • Bilirubin < 20.0mg/dL (if Gilberts then < 2.5 mg/dL) and AST/AST < 2.5 ULN

Exclusion Criteria:

  • Richter's syndrome, Burkitt's lymphoma, or Burkitt-like Lymphoma (transformed DLBCL from Follicular NHL are eligible).
  • Prior transplant with stem cell infusion 90 days or active graft-versus-host treatment within 8 weeks of Day 1.
  • Prior therapy with SYK inhibitors.
  • Chronic treatment with strong CYP3A4 inhibitor/ inducer, acid reducing agent, Proton pump inhibitors
  • Known lymphomatous involvement of the CNS.
  • Persistent, unresolved NCI CTCAE v4.0 ≥ Grade 2, previous drug-related toxicity (except alopecia, erectile impotence, hot flashes, libido, neuropathy).
  • Prior monoclonal antibody, radioimmunoconjugate, antibody drug conjugate, phototherapy, radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any test agent within 3 weeks or for alemtuzumab 8 weeks of Day 1.
  • For CTCL: (TSEBT) within 12 weeks, or initiation of topical steroid, nitrogen mustard, or topical retinoid within 2 weeks. (Stable topical ≥ 4 weeks prior to Day 1 allowed).
  • Known carrier or infection for HIV/Hep B or C. HCV ab+ must be PCR-. HBV ab+ must be HBsAg- or undetectable DNA
  • Active infection requiring systemic treatment,
  • Significant GI disease, previous major gastric/bowel surgery, difficulty swallowing or malabsorption syndrome.
  • Major surgery within 4 weeks
  • Previous malignancies within 2 yrs. unless relapse risk is small (< 5%).
  • Current use of systemic steroids >20 mg QD prednisone (or equivalent)
  • Breastfeeding or pregnant (intention to become) females or participation in other clinical trials
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01994382
Other Study ID Numbers  ICMJE 13-601
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Portola Pharmaceuticals
Study Sponsor  ICMJE Portola Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Portola Study Director Portola Pharmaceuticals
PRS Account Portola Pharmaceuticals
Verification Date June 2020

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