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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2016 by Portola Pharmaceuticals
Sponsor:
Information provided by (Responsible Party):
Portola Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01994382
First received: November 8, 2013
Last updated: May 9, 2016
Last verified: May 2016
  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

Condition Intervention Phase
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)
Drug: cerdulatinib (PRT062070)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Portola Pharmaceuticals:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) of cerdulatinib in patients with relapsed/refractory CLL/SLL or B-cell NHL. [ Time Frame: Cycle 28 Days until end of treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 days per treatment cycle through end of treatment ] [ Designated as safety issue: No ]
    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 days per treatment cycle through end of treatment ] [ Designated as safety issue: No ]
    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 per treatment cycle through end of treatment ] [ Designated as safety issue: No ]
    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 per treatment cycle through end of treatment ] [ Designated as safety issue: No ]
  • To assess tumor phenotype and genotype in relation to clinical response [ Time Frame: 28 day per treatment cycle through end of treament ] [ Designated as safety issue: No ]
  • 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 per treatment cylce through end of treatment ] [ Designated as safety issue: No ]
    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 per treatment cylce through end of treatment ] [ Designated as safety issue: No ]
  • 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 treatment cylce through end of treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 283
Study Start Date: August 2013
Estimated Study Completion Date: January 2018
Estimated Primary Completion Date: January 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: cerdulatinib (PRT062070)
Intervention: Drug: cerdulatinib (PRT062070) or cerdulatinib (PRT062070) plus rituximab
Drug: cerdulatinib (PRT062070)

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 52 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 40 patients by cancer type. Five cohorts will receive single agent cerdulatinib at a starting dose of 35 mg BID for 28 days escalated to 40 mg BID in the absence of a Grade 3 or higher toxicity. Cohort 2 receives cerdulatinib plus rituximab IV at 375 mg/m2.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  • Submission of formalin-fixed block or 10 slides from lymph node or biopsies if able.
  • 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 > 60 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01994382

Contacts
Contact: Portola Pharmaceuticals 650.246.7000 CerdulatinibStudy@portola.com

Locations
United States, Colorado
Active, not recruiting
Denver, Colorado, United States, 80218
United States, Florida
Recruiting
Sarasota, Florida, United States, 34232
United States, Illinois
Not yet recruiting
Chicago, Illinois, United States, 60637
United States, Maryland
Recruiting
Baltimore, Maryland, United States, 21229
United States, Missouri
Withdrawn
St. Louis, Missouri, United States, 63130
United States, New York
Recruiting
New York, New York, United States, 10065
United States, Tennessee
Active, not recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
Active, not recruiting
Houston, Texas, United States, 77030
Active, not recruiting
San Antonio, Texas, United States, 78229
United States, Wisconsin
Recruiting
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Portola Pharmaceuticals
Investigators
Study Director: Alice Sabalvaro-Torres Portola Pharmaceuticals
  More Information

Responsible Party: Portola Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01994382     History of Changes
Other Study ID Numbers: 13-601 
Study First Received: November 8, 2013
Last Updated: May 9, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Portola Pharmaceuticals:
Leukemia
Lymphocytic
Chronic
B Cell

Additional relevant MeSH terms:
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Lymphoma
Lymphoma, B-Cell
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell
Immune System Diseases
Immunoproliferative Disorders
Leukemia
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on May 26, 2016