Nivolumab and Dasatinib in Treating Patients With Relapsed or Refractory Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

Stopped early · Phase 1

Conditions studied: B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Childhood Acute Lymphoblastic Leukemia, Refractory Adult Acute Lymphoblastic Leukemia, Refractory Childhood Acute Lymphoblastic Leukemia

In brief

The purpose of this research study is to determine the acceptable upper limit dose of nivolumab in combination with dasatinib that may be given to patients with relapsed/refractory philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). Nivolumab is currently Food and Drug Administration (FDA) approved for other cancers, but has not yet been investigated in Ph+ ALL. Dasatinib is currently FDA approved for the treatment of Ph+ ALL, but has not yet been investigated in combination with nivolumab for this disease. There is evidence that dasatinib not only blocks the Philadelphia chromosome or breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1 (BCR-ABL) mutation, but also increases the activity of cells in your immune system. Nivolumab increases T cells in your immune system, which allows your immune system to attack the cancer. We think the combination of these drugs will be more effective against your leukemia than either drug used alone.

Key facts

Study ID

NCT02819804

Run by

Northwestern University

People needed

1

Starts

2017-08-17

Expected to finish

2018-08-30

Last updated by the study team

2020-02-11

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Patients must have a histologically confirmed diagnosis of Ph+ ALL
• Detection of one of the following must be present:
• t(9;22)(q34;q11) or 3-way variant by metaphase cytogenetics
• Breakpoint cluster region (BCR)-Abelson (ABL) positive status by molecular analysis with qualitative polymerase chain reaction (PCR) or fluorescence in situ hybridization (FISH)
• Patients must have primary refractory ALL based on failure to achieve a hematologic or molecular remission after induction therapy with dasatinib and steroids or dasatinib and chemotherapy, or have relapsed after treatment with a tyrosine kinase inhibitor with or without chemotherapy
• Note: Prior course of dasatinib and steroid induction therapy should have included dasatinib 140mg PO daily on days 1-84 and prednisone 60mg/m\^2 (capped at 120mg, or equivalent steroid dose) on days 1-28; if patients were unable to tolerate full steroid dose during induction therapy they will still be eligible
• Note: Patients with refractory or relapsed disease in the central nervous system will be eligible
• Prior chemotherapy or tyrosine kinase inhibitor (TKI) treatment, aside from dasatinib, must be >= 7 days before first investigational agent dose
• Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Patients must have adequate organ and bone marrow function prior to registration, as defined below:
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2 x institutional upper limit of normal (IULN)
• Total bilirubin < 2.0 x IULN (unless Gilbert syndrome has been diagnosed); if leukemia infiltration of the liver is suspected to be causing liver function abnormalities the patient will still be eligible with principal investigator (PI) approval
• Creatinine < 2 x IULN
• Creatinine clearance > 40 mL/min (measured by Cockroft-Gault)
• Females of child-bearing potential (FOCBP) must have a negative pregnancy test within 7 days of registration
• Note: A FOCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy
• Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for > 12 months)
• Women must not be breastfeeding at the time of study registration
• Women and men of reproductive potential should agree to use two effective means of birth control
• For women, contraception should continue for 23 weeks after the last dose of nivolumab and 12 weeks after the last dose of dasatinib to allow complete clearance of drug and its principal metabolites from the body
• For men, contraception should continue for 31 weeks after nivolumab and 12 weeks after dasatinib
• Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study

You may not qualify if…

• Patients may not be receiving any other investigational agents within 5 half-lives of the drug (if known); if the half-life is not known, investigational agents should not be taken within two weeks
• Patients are not eligible if they have an intolerance to most recent prior TKI (other than dasatinib) at the lowest possible effective dose, defined as a grade >= 3 toxicity considered at least possibly related to that TKI; patients are also excluded if they are intolerant or allergic to dasatinib and discontinued prior therapy due to a >= grade 2 treatment related adverse event
• Patients must not have a history of a grade 4 anaphylactic reaction to monoclonal antibody therapy or known hypersensitivity reactions to drugs formulated with polysorbate 90
• Patients must not have had any prior therapy with an anti-PD-1, anti-programmed cell death 1 ligand 1 (PD-L1), anti-programmed cell death 1 ligand 2 (PD-L2), anti-cluster of differentiation (CD)137 or anti-cytotoxic t-lymphocyte-associated protein 4 ligand (CTLA-4) antibody (or any antibody or drug specifically targeting T-cell costimulation or checkpoint pathways; for questions or uncertainties, please contact the PI or quality assurance manager (QAM)
• Patients who have had allogeneic hematopoietic stem cell transplant (HSCT) are not eligible if they meet any of the following:
• transplant is within 2 months from cycle 1, day 1 (C1D1)
• Has clinically significant graft-versus-host disease requiring treatment
• Has >= grade 3 persistent non-hematological toxicity related to the transplant
• Concomitant use of strong inhibitors of the cytochrome p450, family 3, subfamily a, polypeptide 4 (CYP3A4) isoenzyme is not permitted; must have wash-out period of 5 times the half-life of the compound before first dasatinib dose
• Concomitant use of QT prolonging agents strongly associated with torsades de pointes is not permitted
• Patients who have a known dasatinib-resistant ABL-kinase mutation such as T315I are not eligible; for confirmation, please contact PI
• Patients who have any serious or uncontrolled medical disorder that would impair the ability of the subject to receive protocol therapy are not eligible; these include, but are not limited to:
• Active infection that is not well controlled
• Known pleural or pericardial effusion at baseline
• Clinically significant gastrointestinal disease or digestive dysfunction compromising absorption of dasatinib
• Pulmonary arterial hypertension
• Uncontrolled or significant cardiovascular disease, including:
• Myocardial infarction within 6 months of enrollment date
• Uncontrolled angina or congestive heart failure within 3 months of enrollment date
• Left ventricular ejection fraction (LVEF) < 40%
• Significant cardiac conduction abnormality, including:
• History of clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes)
• History of second or third degree heart block (except for second degree type 1)
• Corrected QT (QTc) interval > 500 msec, unless a cardiac pacemaker is present
• Prior malignancy active within the previous 3 years, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancers, superficial bladder cancer, or carcinoma in situ of the prostate, cervix or breast

Where it is running

• Northwestern University — Chicago, Illinois, United States

Full record on ClinicalTrials.gov

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