Clinical Trials Logo

Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT02129062
Other study ID # NCI-2014-00886
Secondary ID NCI-2014-0088620
Status Terminated
Phase Phase 2
First received April 30, 2014
Last updated December 23, 2015
Start date April 2014
Est. completion date November 2015

Study information

Verified date December 2015
Source National Cancer Institute (NCI)
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug Administration
Study type Interventional

Clinical Trial Summary

This phase II trial studies how well ibrutinib works in treating patients with B-cell acute lymphoblastic leukemia that has come back after treatment or has not responded to other treatment. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.


Description:

PRIMARY OBJECTIVES:

I. To evaluate the efficacy of ibrutinib in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) as measured by objective response rate (ORR).

SECONDARY OBJECTIVES:

I. To evaluate the global safety profile of ibrutinib in patients with relapsed or refractory B-ALL.

II. To assess response duration. III. To assess Bruton's tyrosine kinase (BTK) target inhibition, biomarkers, and gene expression profiles in B-ALL patient samples before and during treatment with ibrutinib.

OUTLINE:

Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days.


Recruitment information / eligibility

Status Terminated
Enrollment 20
Est. completion date November 2015
Est. primary completion date November 2015
Accepts healthy volunteers No
Gender Both
Age group 18 Years and older
Eligibility Inclusion Criteria:

- Relapsed or refractory B-ALL due to receive salvage 1, 2, 3, 4, 5, or 6; half of the patients, i.e. 5 out of the first 10 patients, and 5 out of 10 patients thereafter, need to be in earlier line of salvage therapy, defined as 1st, 2nd, or 3rd line of salvage therapy; Philadelphia chromosome-positive (Ph+) B-ALL patients must have failed treatment with at least 1 second generation tyrosine kinase inhibitor; patients in salvage 1 with late relapse should be deemed poor candidates for reinduction with initial therapy; patients with ALL of T cell origin (T-ALL) can not be treated

- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)

- Total bilirubin =< 1.5 × upper limit of normal (ULN) (unless Gilbert's syndrome or disease infiltration of the liver is present)

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.0 × institutional ULN

- Creatinine clearance (Cockcroft-Gault) greater than or equal to 30 mL/min or estimated (est) glomerular filtration rate (GFR) greater than or equal to 30 mL/min/1.73 m^2

- For any surgery or invasive procedure requiring sutures or staples for closure, ibrutinib should be held at least 7 days prior to the intervention and should be held at least 7 days after the procedure, and restarted at the discretion of the investigator when the surgical site is reasonably healed without serosanguineous drainage or the need for drainage tubes

- Bone marrow involvement with >= 5% lymphoblasts, peripheral blast count less than 5,000 per uL

- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; female patients need a negative serum or urine pregnancy test within 14 days of study start (applies only if patient is of childbearing potential); non-childbearing is defined as >= 1 year postmenopausal or surgically sterilized; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of ibrutinib administration

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Patients who receive other chemotherapy; patients must have been off previous therapy for >= 2 weeks and must have recovered from clinically significant toxicity (to grade 1 or less) of all previous therapy prior to enrollment (consent signing) with the following exceptions: steroids, hydroxyurea, oral mercaptopurine, methotrexate, vincristine (including prophylactic intrathecal medication), thioguanine, and tyrosine kinase inhibitors are permitted within 2 weeks of randomization as maintenance or to reduce the peripheral blood blast counts; during ibrutinib therapy, only steroids and hydroxyurea are permitted to reduce peripheral blood blast counts; patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier

- Patients who are receiving any other investigational agents

- Active central nervous system (CNS) leukemia, as defined by unequivocal morphologic evidence of lymphoblasts in the cerebrospinal fluid (CSF), use of CNS-directed local treatment for active disease within the prior 28 days, symptomatic CNS leukemia (i.e., cranial nerve palsies or other significant neurologic dysfunction) within 28 days; prophylactic intrathecal medication is not a reason for exclusion; patients with known brain metastases should be excluded from this clinical trial

- History of allergic reactions attributed to compounds of similar chemical or biologic composition to ibrutinib

- Concomitant use of drugs that strongly inhibit cytochrome P450, family 3, subfamily A, polypeptide 4/5 (CYP3A4/5)

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or an infection requiring systemic antibiotics, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

- Pregnant and breastfeeding women are excluded from this study; breastfeeding should be discontinued if the mother is treated with ibrutinib

- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are eligible, unless the patient's cluster of differentiation (CD)4 count is below the institutional lower limit of normal, or the patient is taking prohibited CYP3A4/5 strong inhibitors or inducers

- Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura (ITP) resulting in (or as evidenced by) declining platelet or hemoglobin (Hgb) levels within the 4 weeks prior to first dose of study drug

- Presence of transfusion-dependent thrombocytopenia

- Prior exposure to ibrutinib

- History of prior malignancy, with the exception of the following:

- Malignancy treated with curative intent and with no evidence of active disease present for more than 3 years prior to screening and felt to be at low risk for recurrence by treating physician

- Adequately treated non-melanomatous skin cancer or lentigo maligna melanoma without current evidence of disease

- Adequately treated cervical carcinoma in situ without current evidence of disease

- Burkitt's or mixed lineage leukemia, T cell ALL

- Isolated extramedullary relapse (i.e., testicular or CNS)

- Patients with a cardiac ejection fraction (as measured by either multi gated acquisition scan [MUGA] or echocardiogram) < 45% are excluded; currently active clinically significant cardiovascular disease such as uncontrolled arrhythmia, congestive heart failure, any class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or history of myocardial infarction within 6 months prior to first dose with study drug

- Unable to swallow capsules, or disease significantly affecting gastrointestinal function and/or inhibiting small intestine absorption, such as malabsorption syndrome, resection of the small bowel, or poorly controlled inflammatory bowel disease affecting the small intestine

- Serologic status reflecting active hepatitis B or C infection; patients that are hepatitis B core antibody positive but antigen negative will need a negative polymerase chain reaction (PCR) prior to enrollment; (hepatitis B antigen or PCR positive patients will be excluded;) (this may not be a necessary exclusion for an ibrutinib monotherapy protocol)

- History of stroke or intracranial hemorrhage within 6 months prior to enrollment

- Current life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the patient's safety, or put the study at risk; any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver or other organ system that may place the subject at undue risk to undergo therapy with ibrutinib

- Any serious medical condition, laboratory abnormality, or psychiatric illness that places the subject at unacceptable risk if he/she were to participate in the study

- Received anticoagulation therapy with warfarin or equivalent vitamin K antagonists within the last 28 days

- Evidence of clinically significant bleeding diathesis or coagulopathy

- Major surgical procedure, open biopsy, or significant traumatic injury, within 28 days prior to day 1, anticipation of need for major surgical procedure during the course of the study; (minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to day 1; bone marrow aspiration +/- biopsy is allowed)

- Prior allogeneic stem cell transplant in previous 3 months

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms

  • Adult B Acute Lymphoblastic Leukemia
  • Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1
  • Burkitt Lymphoma
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Recurrent Adult Acute Lymphoblastic Leukemia

Intervention

Drug:
Ibrutinib
Given PO
Other:
Laboratory Biomarker Analysis
Correlative studies

Locations

Country Name City State
United States University of Chicago Comprehensive Cancer Center Chicago Illinois
United States City of Hope Comprehensive Cancer Center Duarte California
United States Penn State Milton S Hershey Medical Center Hershey Pennsylvania
United States M D Anderson Cancer Center Houston Texas
United States USC / Norris Comprehensive Cancer Center Los Angeles California
United States Rutgers Cancer Institute of New Jersey New Brunswick New Jersey
United States UC Davis Comprehensive Cancer Center LAPS Sacramento California
United States Moffitt Cancer Center Tampa Florida

Sponsors (1)

Lead Sponsor Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Objective response rate ORR will be presented with 95% confidence intervals. The association between ORR and patient and clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test. The two-sided log-rank test will be used to assess the differences of time to events between groups such as age groups, or Philadelphia chromosome-positive versus Philadelphia chromosome-negative B-ALL. 3 months after treatment No
Primary Overall survival time Overall survival time will be estimated using the Kaplan-Meier method. The two-sided log-rank test will be used to assess the differences of time to events between groups such as age groups, or Philadelphia chromosome-positive versus Philadelphia chromosome-negative B-ALL. Up to 30 days after completion of study treatment No
See also
  Status Clinical Trial Phase
Terminated NCT01564277 - Rasburicase and Allopurinol in Treating Patients With Hematologic Malignancies Phase 2
Completed NCT01527045 - Donor Atorvastatin Treatment in Preventing Severe Acute GVHD After Nonmyeloablative Peripheral Blood Stem Cell Transplant in Patients With Hematological Malignancies Phase 2
Completed NCT00897325 - Collecting and Storing Samples of Bone Marrow and Blood From Patients With Relapsed Acute Lymphoblastic Leukemia or Non-Hodgkin Lymphoma
Completed NCT02168140 - CPI-613 and Bendamustine Hydrochloride in Treating Patients With Relapsed or Refractory T-Cell Non-Hodgkin Lymphoma or Hodgkin Lymphoma Phase 1
Terminated NCT02109224 - Ibrutinib in Treating Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma in Patients With HIV Infection Phase 1
Completed NCT01427881 - Cyclophosphamide for Prevention of Graft-Versus-Host Disease After Allogeneic Peripheral Blood Stem Cell Transplantation in Patients With Hematological Malignancies Phase 2
Completed NCT01233921 - Palifermin in Preventing Chronic Graft-Versus-Host Disease in Patients Who Have Undergone Donor Stem Cell Transplant for Hematologic Cancer N/A
Completed NCT01093586 - Donor Umbilical Cord Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies Phase 2
Terminated NCT00387426 - Sunitinib in Treating Patients With Idiopathic Myelofibrosis Phase 2
Completed NCT00078858 - Mycophenolate Mofetil and Cyclosporine in Reducing Graft-Versus-Host Disease in Patients With Hematologic Malignancies or Metastatic Kidney Cancer Undergoing Donor Stem Cell Transplant Phase 1/Phase 2
Completed NCT00052520 - Biological Therapy in Treating Patients With Advanced Myelodysplastic Syndrome, Acute or Chronic Myeloid Leukemia, or Acute Lymphoblastic Leukemia Who Are Undergoing Stem Cell Transplantation Phase 1/Phase 2
Completed NCT00031655 - Reduced Intensity Donor Stem Cell Transplant in Treating Patients With High Risk Acute Lymphocytic Leukemia in Complete Remission Phase 2
Completed NCT00003196 - Low-Dose Total Body Irradiation and Donor Peripheral Blood Stem Cell Transplant Followed by Donor Lymphocyte Infusion in Treating Patients With Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, or Multiple Myeloma N/A
Active, not recruiting NCT00792948 - Combination Chemotherapy With or Without Donor Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia Phase 2
Completed NCT01588015 - Vaccine Therapy in Preventing Cytomegalovirus Infection in Patients With Hematological Malignancies Undergoing Donor Stem Cell Transplant Phase 1
Withdrawn NCT02281279 - Rituximab, Romidepsin, and Lenalidomide in Treating Patients With Recurrent or Refractory B-cell Non-Hodgkin Lymphoma Phase 1/Phase 2
Terminated NCT01383447 - Entinostat And Imatinib Mesylate In Treating Patients With Relapsed or Refractory Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Phase 1/Phase 2
Completed NCT00608361 - Dasatinib in Treating Patients With Solid Tumors or Lymphomas That Are Metastatic or Cannot Be Removed By Surgery Phase 1
Completed NCT00217646 - Sorafenib in Treating Patients With Refractory or Relapsed Acute Leukemia, Myelodysplastic Syndromes, or Blastic Phase Chronic Myelogenous Leukemia Phase 1
Completed NCT00095797 - XK469R in Treating Patients With Refractory Hematologic Cancer Phase 1