Clinical Trials /

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

NCT01994382

Description:

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

Related Conditions:
  • Chronic Lymphocytic Leukemia
  • Diffuse Large B-Cell Lymphoma
  • Follicular Lymphoma
  • Lymphoplasmacytic Lymphoma
  • Mantle Cell Lymphoma
  • Marginal Zone Lymphoma
  • Mycosis Fungoides
  • Peripheral T-Cell Lymphoma
  • Primary Cutaneous T Cell Non-Hodgkin Lymphoma
  • Sezary Syndrome
  • Small Lymphocytic Lymphoma
  • Waldenstrom Macroglobulinemia
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase 1/2A Dose Escalation Study in CLL, SLL or NHL
  • Official Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: 13-601
  • NCT ID: NCT01994382

Conditions

  • 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)

Interventions

DrugSynonymsArms
Cerdulatinib (PRT062070)cerdulatinib (PRT062070)

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
cerdulatinib (PRT062070)ExperimentalIntervention: Drug: cerdulatinib (PRT062070) or cerdulatinib (PRT062070) plus rituximab
  • Cerdulatinib (PRT062070)

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:Assessments: Antitumor activity of cerdulatinib as measured by ORR defined as CR+PR as measured by CT and CT/PET
Measure: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
Safety Issue:
Description: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)
Measure: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
Safety Issue:
Description:Assessments: (Cmax) and area under the plasma concentration versus time curve (AUC) of PRT602070.
Measure: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
Safety Issue:
Description:
Measure:To assess tumor phenotype and genotype in relation to clinical response
Time Frame:28-day cycles until end of treatment
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:Assessments: PE, vitals, laboratory values and AEs
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Portola Pharmaceuticals

Trial Keywords

  • Leukemia
  • Lymphocytic
  • Chronic
  • B Cell

Last Updated

July 25, 2019