Ibrutinib in Treating Patients With Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia

NCT02129062 | Terminated Phase 2 Results DMC

• 5 other identifiers: NCI-2014-008862013-04599543P30CA016672N01CM39
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 8

Brief 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.

Conditions

Adult B Acute Lymphoblastic Leukemia; Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1; Recurrent Adult Acute Lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate (ORR)

  ORR is defined as the proportion of participants with complete or partial response. Response definitions of Complete Response (CR): disappearance of leukemia as indicated by \<5% marrow blasts \& absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by absolute neutrophil count (ANC) \>1000/μL \& platelets \>100,000/μL. C1 extramedullary disease status required. CR with incomplete count recovery (CRi): CR except with ANC \<1000/μL and/or platelets \<100,000/μL. Partial response (PR): improved or no worsening of ALL as indicated by no peripheral blood blasts, neutrophils \>1000/μL, platelets \>100,000μL, and either or both of the following: \>50% decrease in marrow blast percentage, compared to pretreatment value, \& marrow blast percentage ≥ 5% and ≤ 25%. C2 extramedullary disease status. Treatment failures are defined as participants who fail to achieve CR, CRi or PR.

  3 months after treatment

• Overall Survival Time

  The time measurement from beginning treatment to recurrent or progressive disease is objectively documented. 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. Progressive disease is defined as a doubling of the peripheral blasts and an absolute increase of \> 5 x 10\^9/L.

  Up to thirty days after after completion of study treatment anticipated to be 12 weeks for total of 16 weeks

Study Arms (1)

Treatment (ibrutinib)

EXPERIMENTAL

Ibrutinib 560 mg orally daily on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Drug: Ibrutinib; Other: Laboratory Biomarker Analysis

Interventions

Ibrutinib DRUG

Given orally 560 mg daily (dispensed as 4 x 140-mg capsules)

Also known as: BTK Inhibitor PCI-32765, CRA-032765, PCI-32765

Treatment (ibrutinib)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (ibrutinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead
• M.D. Anderson Cancer Center: collaborator

Study Sites (8)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

UC Davis Comprehensive Cancer Center LAPS

Sacramento, California, 95817, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, 17033-0850, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Burkitt Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

ibrutinib

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Lymphoid; Leukemia; Hematologic Diseases

Results Point of Contact

• Title: Jan Burger, MD/ UT MD Anderson Associate Professor, Leukemia
• Organization: UT MD Anderson Cancer Center

CR_Study_Registration@mdanderson.org

713-794-4329

Study Officials

• Jan Burger

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2014
• First Posted: May 2, 2014
• Study Start: April 1, 2014
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: January 16, 2017
• Results First Posted: January 16, 2017

Record last verified: 2016-11

Locations

US (8)