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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00945815
First received: July 23, 2009
Last updated: November 13, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Leukemia
Biological: epratuzumab
Drug: clofarabine
Drug: cytarabine
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • Complete Remission [ Time Frame: After induction therapy was completed (1 or 2 months) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Number of Patients With Grade 3 Through 5 Treatment-Related Adverse Events [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 35
Study Start Date: September 2010
Estimated Study Completion Date: August 2017
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Biological: epratuzumab Drug: clofarabine Drug: cytarabine Other: laboratory biomarker analysis

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).

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00945815

  Show 81 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
Investigators
Study Chair: Anjali Advani, MD The Cleveland Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00945815     History of Changes
Other Study ID Numbers: CDR0000649725, S0910, U10CA032102
Study First Received: July 23, 2009
Results First Received: November 13, 2013
Last Updated: November 13, 2013
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Southwest Oncology Group:
B-cell adult acute lymphoblastic leukemia
L1 adult acute lymphoblastic leukemia
L2 adult acute lymphoblastic leukemia
recurrent adult acute lymphoblastic leukemia

Additional relevant MeSH terms:
Burkitt Lymphoma
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Lymphoma, Non-Hodgkin
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoma, B-Cell
Neoplasms, Experimental
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cytarabine
Clofarabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents

ClinicalTrials.gov processed this record on August 18, 2014