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S0530 Cytarabine and Clofarabine in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00337168
First Posted: June 15, 2006
Last Update Posted: March 25, 2015
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Southwest Oncology Group
  Purpose

RATIONALE: 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 more than one drug (combination chemotherapy) may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving cytarabine together with clofarabine works in treating patients with relapsed or refractory acute lymphoblastic leukemia.


Condition Intervention Phase
Leukemia Drug: clofarabine Drug: cytarabine Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Trial of Cytarabine and Clofarabine in Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL)

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • Number of Patients With Complete Remission [ Time Frame: Between day 28 and day 35 inclusive ]
    Complete remission is defined as: less than 5% bone marrow blasts, neutrophils greater or equal to 1,000 per microliter, platelets greater than 100,000 per microliter, no blasts in the peripheral blood, and no extramedullary disease


Secondary Outcome Measures:
  • Expression of Nucleoside Transporters [ Time Frame: On average, two weeks before treatment started ]
    Expression was examined in paraffin-embedded tissue by immunohistochemistry. Intensities were scored on a 0-2+ scale. High expression was a score of 2+.

  • Number of Patients With Very Poor Risk Cytogenetics [ Time Frame: On average, 2 weeks before treatment started ]
  • Toxicity [ Time Frame: Patients were assess for adverse events after each induction cycle (up to two cycles) and after the one consolidation cycle ]
    Number of patients with Grade 3-5 adverse events that are related to study drug by given type of adverse event


Enrollment: 36
Study Start Date: October 2006
Study Completion Date: January 2013
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Induc, ReInduc, Consol, clofarabine, cytarabine
Induction: 40mg/m2/d; IV over 1 hr; days 1-5 Re-induction (if necessary): 40mg/m2/d; IV over 1 hr; days 1-5 Consolidation: 40mg/m2/d; IV over 1 hr; days 1-4
Drug: clofarabine
Induction: 40mg/m2/d; IV over 1 hr; days 1-5 Re-induction (if necessary): 40mg/m2/d; IV over 1 hr; days 1-5 Consolidation: 40mg/m2/d; IV over 1 hr; days 1-4
Drug: cytarabine
Induction: 1g/m2/d; IV over 2 hrs; days 1-5 Re-induction (if necessary): 1g/m2/d; IV over 2 hrs; days 1-5 Consolidation: 1g/m2/d; IV over 2 hrs; days 1-4

Detailed Description:

Primary objective:

  • Determine whether the complete remission rate in adult patients with relapsed or refractory acute lymphoblastic leukemia (ALL) is sufficiently high after treatment with cytarabine and clofarabine to warrant further investigation.

Secondary objectives:

  • Estimate the frequency and severity of toxicities associated with this dosing schedule of cytarabine and clofarabine.
  • Investigate, preliminarily, the prognostic effects of cytogenetic features on response to treatment in these patients.

Other objectives (if funding allows):

  • Investigate, preliminarily, the prognostic effects of laboratory correlates (expression of nucleoside transporters, expression of other pertinent genes by tissue microarray) and FISH features on response to treatment in these patients

OUTLINE: This is an open-label, multicenter study.

  • Induction therapy (1 or 2 courses): Patients receive induction therapy comprising clofarabine IV over 1 hour followed 4 hours later by cytarabine IV over 2 hours on days 1-5 (course 1). Patients who achieve a response (5-25% blasts in the bone marrow with a ≥ 50% reduction in blasts from initial bone marrow aspirate) receive 1 more course of induction therapy beginning no later than day 45. Patients who achieve complete remission (< 5% blasts in the bone marrow) after 1 or 2 courses of induction therapy may proceed to consolidation therapy.
  • Consolidation therapy (1 course): Beginning within 60 days after the first day of the last induction therapy, patients may receive consolidation therapy comprising clofarabine IV over 1 hour followed 4 hours later by cytarabine IV over 2 hours on days 1-4.

After completion of study treatment, patients are followed periodically for up to 5 years.

PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   16 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Prior morphologic diagnosis of acute lymphoblastic leukemia (ALL)

    • No M0, mixed lineage, or L3 (Burkitt's) ALL
  • Refractory to a standard induction regimen OR relapsed after successful prior induction therapy

    • Standard induction regimen is defined as any program of treatment that includes vincristine and prednisone or high-dose cytarabine/mitoxantrone
    • Any number of inductions or remissions allowed
  • Must have evidence of ALL in bone marrow or peripheral blood

    • Immunophenotyping of the blood or bone marrow lymphoblasts must be performed to determine lineage (B cell, T cell, or mixed B/T cell)
    • No extramedullary only disease in the absence of bone marrow or blood involvement
    • Co-expression of myeloid antigens (CD13 and CD33) allowed
  • Patients with Philadelphia chromosome-positive (Ph+) ALL or bcr/abl-positive ALL who were previously eligible for imatinib mesylate treatment must have received imatinib mesylate either alone or in combination with chemotherapy for ALL and must have either failed treatment or been unable to tolerate treatment
  • No CNS involvement as determined by lumbar puncture (for previous CNS history or clinical signs or symptoms of CNS) or by clinical exam (if no previous history or signs/symptoms)
  • Must be registered on SWOG-S9910 and SWOG-9007

PATIENT CHARACTERISTICS:

  • Zubrod performance status 0-2
  • Creatinine ≤ 1.5 times upper limit of normal (ULN)
  • AST or ALT ≤ 1.5 times ULN
  • Bilirubin ≤ 1.5 times ULN
  • No psychiatric disorders that would interfere with study compliance
  • No uncontrolled systemic fungal, bacterial, viral, or other infection
  • No other severe concurrent disease
  • No other serious or poorly controlled medical condition that would preclude study participation
  • No history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that would preclude study participation
  • HIV negative
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No pre-existing motor or sensory neuropathy ≥ grade 2
  • No other prior malignancies, except for the following:

    • Adequately treated basal cell or squamous cell skin cancer
    • In situ cervical cancer
    • Adequately treated stage I or II cancer in complete remission
    • Any other prior cancer for which the patient has been disease free for ≥ 5 years

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Recovered from prior therapy
  • No prior clofarabine
  • More than 2 weeks since prior chemotherapy, major surgery, or other investigational agents
  • More than 6 weeks since prior monoclonal antibodies
  • Prior allogeneic or autologous bone marrow transplant allowed provided the following criteria are met:

    • More than 90 days since transplant
    • No acute graft-versus-host disease (GVHD) ≥ grade 2 OR moderate or severe limited chronic GVHD OR extensive chronic GVHD of any severity
  • Prior maintenance therapy with steroids, vincristine, and/or anti-metabolite agents, such as, but not limited to, mercaptopurine, thioguanine, or methotrexate allowed
  • Concurrent hydroxyurea allowed
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00337168


  Hide Study Locations
Locations
United States, Alaska
Providence Cancer Center
Anchorage, Alaska, United States, 99508
United States, Arkansas
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
United States, California
Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center
Orange, California, United States, 92868
Stanford Cancer Center
Stanford, California, United States, 94305-5824
United States, Florida
M.D. Anderson Cancer Center at Orlando
Orlando, Florida, United States, 32806
H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
Tampa, Florida, United States, 33612-9497
United States, Georgia
Piedmont Hospital
Atlanta, Georgia, United States, 30309
Northside Hospital Cancer Center
Atlanta, Georgia, United States, 30342-1611
Saint Joseph's Hospital of Atlanta
Atlanta, Georgia, United States, 30342-1701
CCOP - Atlanta Regional
Atlanta, Georgia, United States, 30342
WellStar Cobb Hospital
Austell, Georgia, United States, 30106
Charles B. Eberhart Cancer Center at DeKalb Medical Center
Decatur, Georgia, United States, 30033
Gwinnett Medical Center
Lawrenceville, Georgia, United States, 30045
Kennestone Cancer Center at Wellstar Kennestone Hospital
Marietta, Georgia, United States, 30060
Southern Regional Medical Center
Riverdale, Georgia, United States, 30274-2600
United States, Illinois
Cardinal Bernardin Cancer Center at Loyola University Medical Center
Maywood, Illinois, United States, 60153
United States, Indiana
St. Francis Hospital and Health Centers - Beech Grove Campus
Beech Grove, Indiana, United States, 46107
Reid Hospital & Health Care Services
Richmond, Indiana, United States, 47374
United States, Kansas
Cancer Center of Kansas, PA - Chanute
Chanute, Kansas, United States, 66720
Cancer Center of Kansas, PA - Dodge City
Dodge City, Kansas, United States, 67801
Cancer Center of Kansas, PA - El Dorado
El Dorado, Kansas, United States, 67042
Cancer Center of Kansas, PA - Kingman
Kingman, Kansas, United States, 67068
Southwest Medical Center
Liberal, Kansas, United States, 67901
Cancer Center of Kansas, PA - Newton
Newton, Kansas, United States, 67114
Cancer Center of Kansas, PA - Parsons
Parsons, Kansas, United States, 67357
Cancer Center of Kansas, PA - Pratt
Pratt, Kansas, United States, 67124
Cancer Center of Kansas, PA - Salina
Salina, Kansas, United States, 67042
Tammy Walker Cancer Center at Salina Regional Health Center
Salina, Kansas, United States, 67401
Cancer Center of Kansas, PA - Wellington
Wellington, Kansas, United States, 67152
Associates in Womens Health, PA - North Review
Wichita, Kansas, United States, 67208
Cancer Center of Kansas, PA - Medical Arts Tower
Wichita, Kansas, United States, 67208
Cancer Center of Kansas, PA - Wichita
Wichita, Kansas, United States, 67214
CCOP - Wichita
Wichita, Kansas, United States, 67214
Via Christi Cancer Center at Via Christi Regional Medical Center
Wichita, Kansas, United States, 67214
Wesley Medical Center
Wichita, Kansas, United States, 67214
Cancer Center of Kansas, PA - Winfield
Winfield, Kansas, United States, 67156
United States, Louisiana
Tulane Cancer Center Office of Clinical Research
Alexandria, Louisiana, United States, 71315-3198
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109-0942
United States, Montana
CCOP - Montana Cancer Consortium
Billings, Montana, United States, 59101
Hematology-Oncology Centers of the Northern Rockies - Billings
Billings, Montana, United States, 59101
Northern Rockies Radiation Oncology Center
Billings, Montana, United States, 59101
St. Vincent Healthcare Cancer Care Services
Billings, Montana, United States, 59101
Billings Clinic - Downtown
Billings, Montana, United States, 59107-7000
Bozeman Deaconess Cancer Center
Bozeman, Montana, United States, 59715
St. James Healthcare Cancer Care
Butte, Montana, United States, 59701
Frontier Cancer Center
Great Falls, Montana, United States, 59405
Great Falls Clinic - Main Facility
Great Falls, Montana, United States, 59405
St. Peter's Hospital
Helena, Montana, United States, 59601
Glacier Oncology, PLLC
Kalispell, Montana, United States, 59901
Kalispell Medical Oncology at KRMC
Kalispell, Montana, United States, 59901
Kalispell Regional Medical Center
Kalispell, Montana, United States, 59901
Community Medical Center
Missoula, Montana, United States, 59801
Guardian Oncology and Center for Wellness
Missoula, Montana, United States, 59804
Montana Cancer Specialists at Montana Cancer Center
Missoula, Montana, United States, 59807-7877
Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
Missoula, Montana, United States, 59807
United States, New York
James P. Wilmot Cancer Center at University of Rochester Medical Center
Rochester, New York, United States, 14642
United States, Ohio
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195
Grandview Hospital
Dayton, Ohio, United States, 45405
Good Samaritan Hospital
Dayton, Ohio, United States, 45406
David L. Rike Cancer Center at Miami Valley Hospital
Dayton, Ohio, United States, 45409
Samaritan North Cancer Care Center
Dayton, Ohio, United States, 45415
Veterans Affairs Medical Center - Dayton
Dayton, Ohio, United States, 45428
CCOP - Dayton
Dayton, Ohio, United States, 45429
Blanchard Valley Medical Associates
Findlay, Ohio, United States, 45840
Middletown Regional Hospital
Franklin, Ohio, United States, 45005-1066
Community Oncology Group at Cleveland Clinic Cancer Center
Independence, Ohio, United States, 44131
Charles F. Kettering Memorial Hospital
Kettering, Ohio, United States, 45429
UVMC Cancer Care Center at Upper Valley Medical Center
Troy, Ohio, United States, 45373-1300
Clinton Memorial Hospital
Wilmington, Ohio, United States, 45177
Cleveland Clinic - Wooster
Wooster, Ohio, United States, 44691
Ruth G. McMillan Cancer Center at Greene Memorial Hospital
Xenia, Ohio, United States, 45385
United States, South Carolina
Hollings Cancer Center at Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Texas
Baylor University Medical Center - Houston
Houston, Texas, United States, 77030
Ben Taub General Hospital
Houston, Texas, United States, 77030
Methodist Hospital
Houston, Texas, United States, 77030
St. Luke's Texas Cancer Institute at St. Luke's Episcopal Hospital
Houston, Texas, United States, 77030
Veterans Affairs Medical Center - Houston
Houston, Texas, United States, 77030
CCOP - Scott and White Hospital
Temple, Texas, United States, 76508
United States, Utah
Huntsman Cancer Institute at University of Utah
Salt Lake City, Utah, United States, 84112
United States, Washington
St. Joseph Cancer Center
Bellingham, Washington, United States, 98225
Olympic Hematology and Oncology
Bremerton, Washington, United States, 98310
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98104
Harborview Medical Center
Seattle, Washington, United States, 98104
Minor and James Medical, PLLC
Seattle, Washington, United States, 98104
Group Health Central Hospital
Seattle, Washington, United States, 98112
Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
Seattle, Washington, United States, 98122-4307
Polyclinic First Hill
Seattle, Washington, United States, 98122
University Cancer Center at University of Washington Medical Center
Seattle, Washington, United States, 98195-6043
Cancer Care Northwest - Spokane South
Spokane, Washington, United States, 99202
Wenatchee Valley Medical Center
Wenatchee, Washington, United States, 98801-2028
United States, Wyoming
Welch Cancer Center at Sheridan Memorial Hospital
Sheridan, Wyoming, United States, 82801
Sponsors and Collaborators
Southwest Oncology Group
National Cancer Institute (NCI)
Investigators
Study Chair: Anjali Advani, MD The Cleveland Clinic
Principal Investigator: Jerry Radich, MD Fred Hutchinson Cancer Research Center
  More Information

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00337168     History of Changes
Other Study ID Numbers: S0530
U10CA032102 ( U.S. NIH Grant/Contract )
SWOG-S0530 ( Other Identifier: SWOG )
First Submitted: June 13, 2006
First Posted: June 15, 2006
Results First Submitted: June 5, 2012
Results First Posted: July 10, 2012
Last Update Posted: March 25, 2015
Last Verified: March 2015

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

Additional relevant MeSH terms:
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cytarabine
Clofarabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs