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

Leukemia Clinical Trial

Official title:

A Phase II Trial of Cytarabine and Clofarabine in Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00337168
• Other study ID #: S0530
• Secondary ID: U10CA032102SWOG-
• Status: Completed
• Phase: Phase 2
• First received: June 13, 2006
• Last updated: March 5, 2015
• Start date: October 2006
• Est. completion date: January 2013

Study information

• Verified date: March 2015
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: January 2013
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years and older

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

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
• 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

Locations

Country	Name	City	State
United States	Tulane Cancer Center Office of Clinical Research	Alexandria	Louisiana
United States	Providence Cancer Center	Anchorage	Alaska
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	CCOP - Atlanta Regional	Atlanta	Georgia
United States	Northside Hospital Cancer Center	Atlanta	Georgia
United States	Piedmont Hospital	Atlanta	Georgia
United States	Saint Joseph's Hospital of Atlanta	Atlanta	Georgia
United States	WellStar Cobb Hospital	Austell	Georgia
United States	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana
United States	St. Joseph Cancer Center	Bellingham	Washington
United States	Billings Clinic - Downtown	Billings	Montana
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana
United States	Northern Rockies Radiation Oncology Center	Billings	Montana
United States	St. Vincent Healthcare Cancer Care Services	Billings	Montana
United States	Bozeman Deaconess Cancer Center	Bozeman	Montana
United States	Olympic Hematology and Oncology	Bremerton	Washington
United States	St. James Healthcare Cancer Care	Butte	Montana
United States	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas
United States	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	CCOP - Dayton	Dayton	Ohio
United States	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio
United States	Good Samaritan Hospital	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Samaritan North Cancer Care Center	Dayton	Ohio
United States	Veterans Affairs Medical Center - Dayton	Dayton	Ohio
United States	Charles B. Eberhart Cancer Center at DeKalb Medical Center	Decatur	Georgia
United States	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas
United States	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas
United States	Blanchard Valley Medical Associates	Findlay	Ohio
United States	Middletown Regional Hospital	Franklin	Ohio
United States	Frontier Cancer Center	Great Falls	Montana
United States	Great Falls Clinic - Main Facility	Great Falls	Montana
United States	St. Peter's Hospital	Helena	Montana
United States	Baylor University Medical Center - Houston	Houston	Texas
United States	Ben Taub General Hospital	Houston	Texas
United States	Methodist Hospital	Houston	Texas
United States	St. Luke's Texas Cancer Institute at St. Luke's Episcopal Hospital	Houston	Texas
United States	Veterans Affairs Medical Center - Houston	Houston	Texas
United States	Community Oncology Group at Cleveland Clinic Cancer Center	Independence	Ohio
United States	Glacier Oncology, PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology at KRMC	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Charles F. Kettering Memorial Hospital	Kettering	Ohio
United States	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas
United States	Gwinnett Medical Center	Lawrenceville	Georgia
United States	Southwest Medical Center	Liberal	Kansas
United States	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Kennestone Cancer Center at Wellstar Kennestone Hospital	Marietta	Georgia
United States	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois
United States	Community Medical Center	Missoula	Montana
United States	Guardian Oncology and Center for Wellness	Missoula	Montana
United States	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana
United States	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana
United States	Cancer Center of Kansas, PA - Newton	Newton	Kansas
United States	Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center	Orange	California
United States	M.D. Anderson Cancer Center at Orlando	Orlando	Florida
United States	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas
United States	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas
United States	Reid Hospital & Health Care Services	Richmond	Indiana
United States	Southern Regional Medical Center	Riverdale	Georgia
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	Cancer Center of Kansas, PA - Salina	Salina	Kansas
United States	Tammy Walker Cancer Center at Salina Regional Health Center	Salina	Kansas
United States	Huntsman Cancer Institute at University of Utah	Salt Lake City	Utah
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Group Health Central Hospital	Seattle	Washington
United States	Harborview Medical Center	Seattle	Washington
United States	Minor and James Medical, PLLC	Seattle	Washington
United States	Polyclinic First Hill	Seattle	Washington
United States	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington
United States	University Cancer Center at University of Washington Medical Center	Seattle	Washington
United States	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming
United States	Cancer Care Northwest - Spokane South	Spokane	Washington
United States	Stanford Cancer Center	Stanford	California
United States	H. Lee Moffitt Cancer Center and Research Institute at University of South Florida	Tampa	Florida
United States	CCOP - Scott and White Hospital	Temple	Texas
United States	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio
United States	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas
United States	Wenatchee Valley Medical Center	Wenatchee	Washington
United States	Associates in Womens Health, PA - North Review	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas
United States	CCOP - Wichita	Wichita	Kansas
United States	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas
United States	Wesley Medical Center	Wichita	Kansas
United States	Clinton Memorial Hospital	Wilmington	Ohio
United States	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas
United States	Cleveland Clinic - Wooster	Wooster	Ohio
United States	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Southwest Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Patients With Complete Remission	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	Between day 28 and day 35 inclusive	No
Secondary	Expression of Nucleoside Transporters	Expression was examined in paraffin-embedded tissue by immunohistochemistry. Intensities were scored on a 0-2+ scale. High expression was a score of 2+.	On average, two weeks before treatment started	No
Secondary	Number of Patients With Very Poor Risk Cytogenetics		On average, 2 weeks before treatment started	No
Secondary	Toxicity	Number of patients with Grade 3-5 adverse events that are related to study drug by given type of adverse event	Patients were assess for adverse events after each induction cycle (up to two cycles) and after the one consolidation cycle	Yes