Clinical trial NCT00945815: S0910 Epratuzumab, Cytarabine, and Clofarabine in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Keywords: B-cell adult acute lymphoblastic leukemia
L1 adult acute lymphoblastic leukemia
L2 adult acute lymphoblastic leukemia
recurrent adult acute lymphoblastic leukemia
Lead sponsor: SWOG Cancer Research Network
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-07-24
Enrollment: 35
Sex: ALL
Minimum age (years): 16
Maximum age (years): 120
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

Eligibility 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)

Primary outcomes:
measure: Complete Remission
timeFrame: After induction therapy was completed (1 or 2 months)
Secondary outcomes:
measure: Number of Patients With Grade 3 Through 5 Treatment-Related Adverse Events
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
state: Arkansas
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center and Hospital
state: California
city: Sacramento
country: United States
facility: University of California Davis Cancer Center
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center at UC Health Sciences Center
state: Colorado
city: Grand Junction
country: United States
facility: St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center
state: Colorado
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
state: Florida
city: Maywood
country: United States
facility: Cardinal Bernardin Cancer Center at Loyola University Medical Center
state: Illinois
city: Beech Grove
country: United States
facility: St. Francis Hospital and Health Centers - Beech Grove Campus
state: Indiana
city: Richmond
country: United States
facility: Reid Hospital & Health Care Services
state: Indiana
city: Alexandria
country: United States
facility: Tulane Cancer Center Office of Clinical Research
state: Louisiana
city: Baton Rouge
country: United States
facility: Hematology-Oncology Clinic
state: Louisiana
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Jackson
country: United States
facility: University of Mississippi Cancer Clinic
state: Mississippi
city: Saint Louis
country: United States
facility: Saint Louis University Cancer Center
state: Missouri
city: Billings
country: United States
facility: CCOP - Montana Cancer Consortium
state: Montana
city: Billings
country: United States
facility: St. Vincent Healthcare Cancer Care Services
state: Montana
city: Billings
country: United States
facility: Hematology-Oncology Centers of the Northern Rockies - Billings
state: Montana
city: Billings
country: United States
facility: Billings Clinic - Downtown
state: Montana
city: Bozeman
country: United States
facility: Bozeman Deaconess Cancer Center
state: Montana
city: Great Falls
country: United States
facility: Great Falls Clinic - Main Facility
state: Montana
city: Great Falls
country: United States
facility: Sletten Cancer Institute at Benefis Healthcare
state: Montana
city: Helena
country: United States
facility: St. Peter's Hospital
state: Montana
city: Kalispell
country: United States
facility: Glacier Oncology, PLLC
state: Montana
city: Kalispell
country: United States
facility: Kalispell Regional Medical Center
state: Montana
city: Missoula
country: United States
facility: Montana Cancer Specialists at Montana Cancer Center
state: Montana
city: Missoula
country: United States
facility: Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
state: Montana
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center at University of Rochester Medical Center
state: New York
city: Charlotte
country: United States
facility: Presbyterian Cancer Center at Presbyterian Hospital
state: North Carolina
city: Cincinnati
country: United States
facility: Charles M. Barrett Cancer Center at University Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Dayton
country: United States
facility: Grandview Hospital
state: Ohio
city: Dayton
country: United States
facility: Good Samaritan Hospital
state: Ohio
city: Dayton
country: United States
facility: David L. Rike Cancer Center at Miami Valley Hospital
state: Ohio
city: Dayton
country: United States
facility: Samaritan North Cancer Care Center
state: Ohio
city: Dayton
country: United States
facility: CCOP - Dayton
state: Ohio
city: Findlay
country: United States
facility: Blanchard Valley Medical Associates
state: Ohio
city: Franklin
country: United States
facility: Middletown Regional Hospital
state: Ohio
city: Greenville
country: United States
facility: Wayne Hospital
state: Ohio
city: Kettering
country: United States
facility: Charles F. Kettering Memorial Hospital
state: Ohio
city: Troy
country: United States
facility: UVMC Cancer Care Center at Upper Valley Medical Center
state: Ohio
city: Xenia
country: United States
facility: Ruth G. McMillan Cancer Center at Greene Memorial Hospital
state: Ohio
city: Charleston
country: United States
facility: Hollings Cancer Center at Medical University of South Carolina
state: South Carolina
city: Greenville
country: United States
facility: Cancer Centers of the Carolinas - Faris Road
state: South Carolina
city: Greenville
country: United States
facility: Cancer Centers of the Carolinas - Grove Commons
state: South Carolina
city: Greenville
country: United States
facility: CCOP - Greenville
state: South Carolina
city: Greer
country: United States
facility: Cancer Centers of the Carolinas - Greer Medical Oncology
state: South Carolina
city: Seneca
country: United States
facility: Cancer Centers of the Carolinas - Seneca
state: South Carolina
city: Spartanburg
country: United States
facility: Cancer Centers of the Carolinas - Spartanburg
state: South Carolina
city: Houston
country: United States
facility: Baylor University Medical Center - Houston
state: Texas
city: Houston
country: United States
facility: Ben Taub General Hospital
state: Texas
city: Houston
country: United States
facility: St. Luke's Texas Cancer Institute at St. Luke's Episcopal Hospital
state: Texas
city: Houston
country: United States
facility: Veterans Affairs Medical Center - Houston
state: Texas
city: American Fork
country: United States
facility: American Fork Hospital
state: Utah
city: Cedar City
country: United States
facility: Sandra L. Maxwell Cancer Center
state: Utah
city: Logan
country: United States
facility: Logan Regional Hospital
state: Utah
city: Murray
country: United States
facility: Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
state: Utah
city: Ogden
country: United States
facility: Val and Ann Browning Cancer Center at McKay-Dee Hospital Center
state: Utah
city: Provo
country: United States
facility: Utah Valley Regional Medical Center - Provo
state: Utah
city: Saint George
country: United States
facility: Dixie Regional Medical Center - East Campus
state: Utah
city: Salt Lake City
country: United States
facility: LDS Hospital
state: Utah
city: Anacortes
country: United States
facility: Island Hospital Cancer Care Center at Island Hospital
state: Washington
city: Bellingham
country: United States
facility: St. Joseph Cancer Center
state: Washington
city: Bremerton
country: United States
facility: Olympic Hematology and Oncology
state: Washington
city: Burien
country: United States
facility: Highline Medical Center Cancer Center
state: Washington
city: Issaquah
country: United States
facility: Swedish Medical Center - Issaquah Campus
state: Washington
city: Kennewick
country: United States
facility: Columbia Basin Hematology
state: Washington
city: Mount Vernon
country: United States
facility: Skagit Valley Hospital Cancer Care Center
state: Washington
city: Poulsbo
country: United States
facility: Harrison Poulsbo Hematology and Onocology
state: Washington
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Seattle
country: United States
facility: Group Health Central Hospital
state: Washington
city: Seattle
country: United States
facility: Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
state: Washington
city: Seattle
country: United States
facility: Polyclinic First Hill
state: Washington
city: Seattle
country: United States
facility: University Cancer Center at University of Washington Medical Center
state: Washington
city: Sedro-Woolley
country: United States
facility: North Puget Oncology at United General Hospital
state: Washington
city: Spokane
country: United States
facility: Cancer Care Northwest - Spokane South
state: Washington
city: Spokane
country: United States
facility: Evergreen Hematology and Oncology, PS
state: Washington
city: Wenatchee
country: United States
facility: Wenatchee Valley Medical Center
state: Washington
city: Sheridan
country: United States
facility: Welch Cancer Center at Sheridan Memorial Hospital
state: Wyoming
Study officials:
affiliation: The Cleveland Clinic
name: Anjali Advani, MD
role: STUDY_CHAIR
References:
citation: Statler A, Othus M, Erba HP, Chauncey TR, Radich JP, Coutre S, Advani A, Nand S, Ravandi F, Mukherjee S, Sekeres MA. Comparable outcomes of patients eligible vs ineligible for SWOG leukemia studies. Blood. 2018 Jun 21;131(25):2782-2788. doi: 10.1182/blood-2018-01-826693. Epub 2018 Apr 4.