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

• Status: Active, not recruiting
• Trial end date: 2020-12-01
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Portola Pharmaceuticals

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