S0910 Epratuzumab, Cytarabine, and Clofarabine in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia

Tracking Information
First Submitted Date ICMJE	July 23, 2009
First Posted Date ICMJE	July 24, 2009
Results First Submitted Date	November 13, 2013
Results First Posted Date	January 3, 2014
Last Update Posted Date	November 6, 2017
Study Start Date ICMJE	September 2010
Actual Primary Completion Date	March 2013 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: November 13, 2013)	Complete Remission [ Time Frame: After induction therapy was completed (1 or 2 months) ]; Complete remission (CR) is defined as: <5% marrow aspirate blasts. Blasts can be >=5% if the blasts are found to be myeloid and there is no evidence of lymphoblasts by flow cytometry or immunostaining. Neutrophils >= 1000/mcl; platelets >100,000/mcl; and no blasts in the peripheral blood. C1 Extramedullary disease status as defined in the protocol. Complete remission with incomplete platelet recovery (CRi) is same as CR but platelet count may be <=100,000/mcl and/or ANC may be <1,000/mcl.
Original Primary Outcome Measures ICMJE; (submitted: July 23, 2009)	Complete remission (CR) rate (CR and incomplete CR); Frequency and severity of toxicities
Change History	Complete list of historical versions of study NCT00945815 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: November 13, 2013)	Number of Patients With Grade 3 Through 5 Treatment-Related Adverse Events [ Time Frame: Up to 5 years ]; Only adverse events that are possibly, probably or definitely related to study drug are reported. Any CTCAE 4.0 event of Grade 3 (severe), Grade 4 (life threatening), or Grade 5 (fatal) which were deemed to be related to protocol treatment are included.
Original Secondary Outcome Measures ICMJE	Not Provided
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	S0910 Epratuzumab, Cytarabine, and Clofarabine in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia
Official Title ICMJE	S0910, A Phase II Study of Epratuzumab (NSC-716711) in Combination With Cytarabine and Clofarabine for Patients With Relapsed or Refractory Ph- Negative Precursor B-Cell Acute Lymphoblastic Leukemia
Brief Summary	RATIONALE: Monoclonal antibodies, such as epratuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as cytarabine and clofarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving epratuzumab together with cytarabine and clofarabine may kill more cancer cells. PURPOSE: This phase II trial is studying the side effects and how well giving epratuzumab together with cytarabine and clofarabine works in treating patients with relapsed or refractory acute lymphoblastic leukemia.
Detailed Description	OBJECTIVES: To test whether the complete remission (CR) rate (CR and incomplete CR) in adult patients with relapsed or refractory precursor B-cell acute lymphoblastic leukemia is sufficiently high after treatment with cytarabine, clofarabine, and epratuzumab to warrant further investigation.; To estimate the frequency and severity of toxicities associated with the dosing schedule of cytarabine, clofarabine, and epratuzumab used in this study.; To investigate, preliminarily, the effect of laboratory correlates (minimal post-treatment residual disease) and cytogenetic factors on prognosis in this patient population. (Not reported here due to limited MRD data) OUTLINE: This is a multicenter study. Patients receive cytarabine IV over 2 hours on days 1-5, clofarabine IV over 1 hour on days 2-6, and epratuzumab IV over at least 1 hour on days 7, 14, 21, and 28 in the absence of disease progression or unacceptable toxicity*. NOTE: * Prophylactic intrathecal methotrexate is required for patients < 22 years of age, and is recommended (but not required) for patients ≥ 22 years of age. Blood samples, bone marrow samples, and/or tumor tissue samples may be collected for further laboratory analysis. Patients are followed up every 3 months for 2 years, then annually for 3 years (until 5 years after registration).
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Leukemia
Intervention ICMJE	Biological: epratuzumab; Drug: clofarabine; Drug: cytarabine; Other: laboratory biomarker analysis
Study Arms	Experimental: treatment; AraC 1 g/m2/d IV Days 1-5 clofarabine 40 mg/m2/d IV Days 2-6 epratuzumab 360 mg/m2/d IV Days 7, 14, 21, 28 acetaminophen 650 mg/d PO Days 7, 14, 21, 28 diphenhydramine 50 mg/d IV Days 7, 14, 21, 28 IT methotrexate 12 mg IT at least 1 wk apart during induction All give 1 cycle; Interventions: Biological: epratuzumab; Drug: clofarabine; Drug: cytarabine; Other: laboratory biomarker analysis
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: July 23, 2009)	35
Original Estimated Enrollment ICMJE	Same as current
Actual Study Completion Date	August 2017
Actual Primary Completion Date	March 2013 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	DISEASE CHARACTERISTICS: Morphologically confirmed precursor B-cell acute lymphoblastic leukemia (ALL) (non T-cell) Must have evidence of disease in bone marrow or peripheral blood Immunophenotyping of the blood or marrow lymphoblasts must be performed to determine lineage (B cell, T cell, or mixed B/T cell) Must have ≥ 5% lymphoblasts present in the blood or bone marrow At least 20% of marrow and/or peripheral blood lymphoblasts must be CD22+ by flow cytometry Co-expression of myeloid antigens (CD13 and CD33) allowed Patients with only extramedullary disease in the absence of bone marrow or blood involvement are not eligible; Philadelphia (Ph) chromosome-negative disease Patients with unknown Ph status by cytogenetics or FISH and unknown BCR/ABL status by PCR are eligible for study registration, but must be removed from study therapy if found to be Ph+ or BCR/ABL+ after study registration; Refractory to a standard induction regimen that included vincristine and prednisone or high-dose cytarabine or mitoxantrone OR relapsed after successful prior induction therapy Any number of prior induction therapies or any number of remissions achieved are allowed; No M0 acute myeloid leukemia, mixed lineage leukemia, or L3 (Burkitt) leukemia; No active CNS involvement by clinical evaluation Patients with a documented history of CNS involvement of ALL or with clinical signs or symptoms consistent with CNS involvement of ALL must undergo a lumbar puncture that is negative for CNS involvement of ALL; Patients < 22 years of age must be willing to receive prophylactic intrathecal chemotherapy; Must be registered on SWOG-9007 "Cytogenetic Studies in Leukemia Patients" (closed as of 07/01/2010) PATIENT CHARACTERISTICS: Zubrod performance status 0-2; Serum creatinine ≤ 1.0 mg/dL OR glomerular filtration rate > 60 mL/min; AST and ALT ≤ 2.5 times upper limit of normal (ULN); Alkaline phosphatase ≤ 2.5 times ULN; Bilirubin ≤ 1.5 times ULN; Not pregnant or nursing; Fertile patients must use effective contraception during and for ≥ 6 months after completion of study treatment; HIV-positive patients are eligible (at the discretion of the investigator) provided the following criteria are met: No history of AIDS-defining conditions CD4 cell count > 350/mm³ If on antiretroviral agents, must not include zidovudine or stavudine Willing to receive prophylaxis for pneumocystis jirovecii pneumonia during study therapy (regardless of CD4 cell count) until the CD4 cell count is > 200/mm³ after completion of study treatment; Prior malignancy (other than ALL) allowed provided it is in remission and there are no plans to treat the malignancy at the time of study registration; No uncontrolled systemic fungal, bacterial, viral, or other infection, defined as exhibiting ongoing signs or symptoms related to the infection with no improvement despite appropriate antibiotics or other treatment; No neuropathy (cranial, motor or sensory) ≥ grade 2 PRIOR CONCURRENT THERAPY: See Disease Characteristics; Any number of prior therapies allowed; More than 90 days since prior allogeneic bone marrow transplant (BMT) No concurrent immunosuppression therapy for the treatment of graft-vs-host disease (GVHD) No acute GVHD ≥ grade 2, moderate or severe limited chronic GVHD, or extensive chronic GVHD of any severity; Prior autologous BMT allowed No concurrent immunosuppression therapy for the treatment of GVHD; More than 14 days since prior chemotherapy, investigational agents, or major surgery and recovered Maintenance therapy with steroids, vincristine, and/or anti-metabolite agents, including but not limited to, mercaptopurine, thioguanine, and methotrexate allowed Concurrent hydroxyurea to reduce WBC to a reasonable level (as deemed by the treating physician) allowed; No prior clofarabine or epratuzumab; No other concurrent cytotoxic therapy or investigational therapy; No concurrent alternative medications (e.g., herbal or botanical medications for anticancer purposes); Concurrent participation on SWOG-S9910 "Leukemia Centralized Reference Laboratories and Tissue Repositories, Ancillary" allowed (closed as of 07/01/2010)
Sex/Gender	Sexes Eligible for Study: All
Ages	16 Years to 120 Years (Child, Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00945815
Other Study ID Numbers ICMJE	S0910; S0910 ( Other Identifier: SWOG ); U10CA032102 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Southwest Oncology Group
Study Sponsor ICMJE	Southwest Oncology Group
Collaborators ICMJE	National Cancer Institute (NCI)
Investigators ICMJE	Study Chair: Anjali Advani, MD The Cleveland Clinic
PRS Account	Southwest Oncology Group
Verification Date	October 2017
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP