Sotrastaurin Acetate in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Leukemia, Prolymphocytic Leukemia, or Richter’s Transformation

Learn more about:
Related Clinical Trial
Safety & Efficacy Study of Epcoritamab in Subjects With R/R Chronic Lymphocytic Leukemia and Richter’s Syndrome ALX148, Rituximab and Lenalidomide for the Treatment of Indolent and Aggressive B-cell Non-Hodgkin Lymphoma R-EPOCH in Combination With Ibrutinib for Patients With Classical RT of CLL Phase 1 Study VIP152 in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia or Richter Syndrome A Study to Evaluate the Efficacy and Safety of Obinutuzumab, Ibrutinib, and Venetoclax in Patients With Richter’s Syndrome; Study of Cosibelimab in Subjects With Relapsed or Refractory Lymphoma CD19-Directed CAR-T Cell Therapy for the Treatment of Relapsed/Refractory B Cell Malignancies Study of TG-1801 Alone or in Combination With Ublituximab in Subjects With B-Cell Lymphoma or Chronic Lymphocytic Leukemia Study of Oral Administration of LP-118 in Patients With Relapsed or Refractory NHL, RT, MM, T-PLL, Acute Leukemia (AML, ALL), MDS, MDS/MPN, and MF Ipilimumab, Ibrutinib, and Nivolumab for the Treatment of Chronic Lymphocytic Leukemia and Richter Transformation Polatuzumab Vedotin in Combination With Chemotherapy in Subjects With Richter’s Transformation Autologous Stem Cell Transplant Followed by Polatuzumab Vedotin in Patients With B-cell Non-Hodgkin and Hodgkin Lymphoma Venetoclax in Combination With Ublituximab and Umbralisib (TGR-1202) in Patients With Relapsed or Refractory CLL/SLL Ex Vivo-activated Autologous Lymph Node Lymphocytes in Treating Patients With Chronic Lymphocytic Leukemia Allogeneic Stem Cell Transplant for CLL Study of a Triple Combination Therapy, DTRM-555, in Patients With R/R CLL or R/R Non-Hodgkin’s Lymphomas Atezolizumab, Gemcitabine, Oxaliplatin, and Rituximab in Treating Patients With Relapsed or Refractory Transformed Diffuse Large B-Cell Lymphoma Atezolizumab, Obinutuzumab, and Venetoclax in Treating Patients With Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or Relapsed or Refractory Richter Syndrome Duvelisib and Nivolumab in Treating Patients With Richter Syndrome or Transformed Follicular Lymphoma Sotrastaurin Acetate in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Leukemia, Prolymphocytic Leukemia, or Richter’s Transformation Registry of the German CLL Study Group Nivolumab and Ibrutinib in Treating Patients With Relapsed, Refractory, or High-Risk Untreated Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or Richter Transformation ACP-196 (Acalabrutinib), a Novel Bruton Tyrosine Kinase (Btk) Inhibitor, for Treatment of Chronic Lymphocytic Leukemia A Study of Acalabrutinib and Vistusertib in Subjects With Relapsed/Refractory B-cell Malignancies Study of Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone (CHOP) With Ofatumumab in Patients With Richter’s Syndrome PNT2258 for Treatment of Patients With Richter’s Transformation (Brighton) Study of Immunotherapy in Combination With Ublituximab and Umbralisib in Patients With Relapsed-refractory CLL or Richter’s Transformation Efficacy and Safety of Zanubrutinib Plus Tislelizumab for Treatment of Patients With Richter Transformation BLINAtumomab After R-CHOP Debulking Therapy for Patients With Richter Transformation Oxaliplatin, Fludarabine, Cytarabine, and Rituximab in Patients With Richter’s Transformation and Leukemias Obinutuzumab Containing Conditioning Regimen for Patients With Poor Risk CLL or Richter`s Transformation Requiring Allogeneic Stem Cell Transplantation Study of Pembrolizumab (MK-3475) in Participants With Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma or Relapsed or Refractory Richter Syndrome (MK-3475-170/KEYNOTE-170) Duvelisib and Venetoclax in Relapsed or Refractory CLL or SLL or RS Study of Blinatumomab in Richter Transformation Genomic and Proteomic Study of Richter Syndrome (CGPSR) CRC043: A Phase II Study of Venetoclax in Combination With Dose-adjusted EPOCH-R for Patients With Richter’s Syndrome Study of Ibrutinib & Obinutuzumab With/Without CHOP for Richter’s Transformation or Richter’s Syndrome Patients Obinutuzumab, High Dose Methylprednisolone (HDMP), and Lenalidomide for the Treatment of Patients With Richter’s Syndrome A Trial of CHOP-R Therapy, With or Without Acalabrutinib, in Patients With Newly Diagnosed Richter’s Syndrome Selinexor in Initial or Refractory and/or Relapsed Richter’s Transformation

Brief Title

Sotrastaurin Acetate in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Leukemia, Prolymphocytic Leukemia, or Richter's Transformation

Official Title

A Phase 2 Feasibility Study of Sotrastaurin for Relapsed and Refractory CLL/SLL/PLL/RT

Brief Summary

      This phase II trial studies how well sotrastaurin acetate works in treating patients with
      chronic lymphocytic leukemia, small lymphocytic leukemia, prolymphocytic leukemia, or
      Richter's transformation that has returned or that does not respond to treatment.
      Sotrastaurin acetate may stop the growth of cancer cells by blocking some of the enzymes
      needed for cell growth.
    

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the objective clinical response rate of AEB071 (sotrastaurin acetate)
      treatment in patients with relapsed or refractory chronic lymphocytic leukemia (CLL)/small
      lymphocytic leukemia (SLL)/prolymphocytic leukemia (PLL)/Richter's transformation (RT).

      SECONDARY OBJECTIVES:

      I. To determine the feasibility and tolerability of long-term administration of a fixed dose
      of AEB071 in patients with relapsed or refractory CLL/SLL/PLL.

      II. To examine select downstream pharmacodynamic effects in this population of patients after
      receiving AEB071 including assessment of the wingless-type MMTV integration site family (WNT)
      signaling pathway.

      III. To determine the feasibility and tolerability of AEB071 treatment in patients with
      relapsed or refractory mantle cell lymphoma (MCL) as well as to gain preliminary data
      regarding efficacy in this patient population.

      TERTIARY OBJECTIVES:

      I. Determine the proportion of patients with select germline and somatic deoxyribonucleic
      acid (DNA) alterations, including in the B-cell receptor (BCR) pathway.

      II. Determine how mutational and transcriptional status in key genes affects response to this
      therapy and may have affected response to prior therapies.

      OUTLINE:

      Patients receive sotrastaurin acetate orally (PO) twice daily (BID) on days 1-28. Courses
      repeat every 28 days in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30 days and then at least
      every 3 months thereafter.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Proportion of CLL/SLL/PLL/RT patients who achieve an objective clinical response, estimated by the number of complete, partial, or partial responses with lymphocytosis divided by the total number of evaluable patients

Secondary Outcome

 Response duration

Condition

Prolymphocytic Leukemia

Intervention

sotrastaurin acetate

Study Arms / Comparison Groups

 Treatment (sotrastaurin acetate)
Description:  Patients receive sotrastaurin acetate PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

0

Start Date

March 12, 2015

Completion Date

March 12, 2015

Primary Completion Date

March 12, 2015

Eligibility Criteria

        Inclusion Criteria:

          -  World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance
             status =< 2

          -  Life expectancy >= 2 months

          -  Appropriate histologic diagnosis (a) or (b):

               -  (a) Histologically documented diagnosis of intermediate or high risk CLL/SLL,
                  B-PLL, and RT arising from CLL/SLL according to the 2008 guidelines, meeting
                  criteria for active disease requiring treatment:

                    -  Evidence of marrow failure as manifested by the development or worsening of
                       anemia or thrombocytopenia (not attributable to autoimmune hemolytic anemia
                       or thrombocytopenia)

                    -  Massive (>= 6 cm below the costal margin), progressive or symptomatic
                       splenomegaly

                    -  Massive nodes (>= 10 cm) or progressive or symptomatic lymphadenopathy

                    -  Autoimmune anemia and/or thrombocytopenia that is poorly responsive to
                       standard therapy

                    -  Constitutional symptoms including any of the following:

                         -  Unintentional weight loss of 10% or more within 6 mos.

                         -  Significant fatigue limiting activity

                         -  Fevers >= 100.5 degrees F for 2 weeks or more without evidence of
                            infection

                         -  Night sweats > 1 month without evidence of infection

                    -  Need for cytoreduction prior to stem cell transplantation

               -  (b) Pathologically documented MCL [defined as either t(11;14) or overexpression
                  of cyclin D1] for the MCL pilot study

          -  Relapsed after or refractory to at least one prior therapy

          -  Willingness to undergo all study-related evaluations and procedures

          -  Ability to understand and willingness to execute a written informed consent document

        Exclusion Criteria:

          -  Prior therapy as follows:

               -  Major surgery within 2 weeks

               -  Corticosteroids greater than 20 mg/day prednisone (or equivalent) within 2 weeks
                  unless used by inhalation or topical route, or unless necessary for premedication
                  before iodinated contrast dye, or for autoimmune hemolytic anemia

               -  Cytotoxic chemotherapy or biologic therapy within 4 weeks, excepting BCR kinase
                  inhibitors for which no wash out is required, or

               -  Nitrosoureas within the 6 weeks of the planned first dose of the study drug

          -  Failure to recover toxicity from prior chemo- or radiotherapy to grade 1

          -  Known active leukemia or lymphoma of the central nervous system (CNS) requiring
             therapy

          -  Inadequate bone marrow function/hematopoietic reserve, except in the case of
             documented bone-marrow involvement: absolute neutrophil count (ANC) < 1 x 10^9/L

          -  Inadequate bone marrow function/hematopoietic reserve, except in the case of
             documented bone-marrow involvement: platelets < 30 x 10^9/L

          -  Serum total bilirubin > 2 x ULN (upper limit of normal)

          -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x ULN, or > 5
             x ULN if CLL/lymphoma is present in the liver

          -  Estimated glomerular filtration rate (GFR) < 30 mL/min

          -  Patients who are receiving treatment with medications that are known to be strong
             inducers or inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4/5
             (CYP3A4/5) and CYP3A4/5 substrates with QT prolongation risk that cannot be
             discontinued prior to study entry

          -  Clinically significant cardiac diseases, including any of the following:

               -  History or presence of ventricular tachyarrhythmia

               -  Presence of unstable/uncontrolled atrial fibrillation (with ventricular rate >
                  100 beats per minute [bpm]); patients with stable atrial fibrillation are
                  eligible provided that they do not meet any of the other exclusion criteria

               -  Angina pectoris or acute myocardial infarction within 3 months of starting study
                  drug

               -  New York Heart Association (NYHA) functional class III or IV heart failure

               -  Labile or uncontrolled hypertension

          -  History of another malignancy that limits survival to less than 2 years in the
             estimate of the investigator; basal and squamous cell cancers of the skin, or squamous
             cell carcinoma of the cervix in situ, which were completely resected or otherwise
             cured, or localized prostate cancer (Gleason < 5) are eligible

          -  Gastrointestinal dysfunction, including motility or malabsorption syndromes or
             inflammatory bowel disease which could limit absorption of AEB071

          -  Known human immunodeficiency virus (HIV) positivity, or active hepatitis B or C
             infection with detectible viral nucleic acid in the blood; testing for these viruses
             is not a required part of screening

          -  Severe systemic infections requiring intravenous antibiotics within the two weeks
             prior to initiation of AEB071

          -  Lactating or pregnant

          -  Women of child-bearing potential or male partners of women of child-bearing potential
             who will not agree to use highly effective method of contraception throughout the
             entire study period and for a minimum of 5 terminal half-lives of AEB071
             (approximately 36 hours) after the last dose of study drug; highly effective
             contraception methods include:

               -  Total abstinence or

               -  Male or female sterilization or

               -  Combination of any two of the following (a+b or a+c or b+c):

                    -  a. Use of oral, injected or implanted hormonal methods of contraception

                    -  b. Placement of an intrauterine device (IUD) or intrauterine system (IUS)

                    -  c. Barrier methods of contraception: condom or occlusive cap (diaphragm or
                       cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal
                       suppository Women are considered post-menopausal and not of child bearing
                       potential if they have had 12 months of natural (spontaneous) amenorrhea
                       with an appropriate clinical profile (e.g. age appropriate, history of
                       vasomotor symptoms) or have had surgical bilateral oophorectomy (with or
                       without hysterectomy) or tubal ligation at least six weeks ago; in the case
                       of oophorectomy alone, only when the reproductive status of the woman has
                       been confirmed by follow up hormone level assessment is she considered not
                       of childbearing potential

          -  Any other life-threatening illness or medical condition that, in the opinion of the
             investigator, could compromise the safety of the patient or interfere with analysis of
             study endpoints
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

James Blachly, MD, , 



Administrative Informations


NCT ID

NCT02285244

Organization ID

OSU-14026

Secondary IDs

NCI-2014-02002

Responsible Party

Sponsor-Investigator

Study Sponsor

James Blachly

Collaborators

 Novartis

Study Sponsor

James Blachly, MD, Principal Investigator, The Ohio State University Wexner Medical Center


Verification Date

April 2017