Protocol Summary

Protocol No.: OCR15356

Sponsor Protocol No.: 13-601; Portola

Study 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)

Principal Investigator(s)
Dang, Nam

Objective
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.

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.

Phase: Phase I/II

Age Group: Adult

Scope: National

Treatment
Cerdulatinib (PRT062070) or cerdulatinib (PRT062070) plus rituximab

Detailed Eligibility
INCLUSION CRITERIA:
1. 18 years old or older.
2. Histologically confirmed CLL/SLL or B-cell Non-Hodgkin lymphoma (DLBCL, FL, MCL, MZL, lymphoplasmacytic lymphoma).
3. 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.
4. Received BCR and/or BCL2 inhibitors were intolerant or had relapsed/refractory disease afterwards.
5. Prior treatment for lymphoid malignancy for progressive /refractory disease
6. >= 1 prior regimen (min 2 cycles) with antibody conjugate, cytotoxic chemotherapy, or TKI alone or in combination.
7. 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
8. Ability to provide diagnostic reports
9. ECOG Score of 0 or 1.
10. Hematologic ANC > 1000/uL and platelet > 75,000/uL,
11. Serum creatinine of 50 mL/min
12. Bilirubin
EXCLUSION CRITERIA:
1. Richter's syndrome, Burkitt's lymphoma, or Burkitt-like Lymphoma (transformed DLBCL from Follicular NHL are eligible).
2. Prior transplant with stem cell infusion 90 days or active graft-versus-host treatment within 8 weeks of Day 1.
3. Prior therapy with SYK inhibitors.
4. Chronic treatment with strong CYP3A4 inhibitor/ inducer, acid reducing agent, Proton pump inhibitors
5. Known lymphomatous involvement of the CNS.
6. Persistent, unresolved NCI CTCAE v4.0 >= Grade 2, previous drug-related toxicity (except alopecia, erectile impotence, hot flashes, libido, neuropathy).
7. 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.
8. 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).
9. Known carrier or infection for HIV/Hep B or C. HCV ab+ must be PCR-. HBV ab+ must be HBsAg- or undetectable DNA
10. Active infection requiring systemic treatment,
11. Significant GI disease, previous major gastric/bowel surgery, difficulty swallowing or malabsorption syndrome.
12. Major surgery within 4 weeks
13. Previous malignancies within 2 yrs. unless relapse risk is small (14. Current use of systemic steroids >20 mg QD prednisone (or equivalent)
15. Breastfeeding or pregnant (intention to become) females or participation in other clinical trials

Applicable Disease Sites
Leukemia
Lymphoma - Non-Hodgkin

Participating Institutions
UF Gainesville : Ashton Monismith

Contact
Ashton Monismith, RN
Phone: +1 352-265-0680 ext. 87657

Email: amonismith@ufl.edu

More Information:
View study listing on ClinicialTrials.gov
http://www.clinicaltrials.gov/ct2/show/
NCT01994382