Clinical trial NCT00337168: S0530 Cytarabine and Clofarabine in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia
Official title: A Phase II Trial of Cytarabine and Clofarabine in Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Keywords: 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
Lead sponsor: SWOG Cancer Research Network
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-06-15
Enrollment: 36
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: Number of Patients With Complete Remission
timeFrame: Between day 28 and day 35 inclusive
Secondary outcomes:
measure: Expression of Nucleoside Transporters
timeFrame: On average, two weeks before treatment started
measure: Number of Patients With Very Poor Risk Cytogenetics
timeFrame: On average, 2 weeks before treatment started
measure: Toxicity
timeFrame: Patients were assess for adverse events after each induction cycle (up to two cycles) and after the one consolidation cycle
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Providence Cancer Center
state: Alaska
city: Little Rock
country: United States
facility: Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
state: Arkansas
city: Orange
country: United States
facility: Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: Orlando
country: United States
facility: M.D. Anderson Cancer Center at Orlando
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
state: Florida
city: Atlanta
country: United States
facility: Piedmont Hospital
state: Georgia
city: Atlanta
country: United States
facility: Northside Hospital Cancer Center
state: Georgia
city: Atlanta
country: United States
facility: Saint Joseph's Hospital of Atlanta
state: Georgia
city: Atlanta
country: United States
facility: CCOP - Atlanta Regional
state: Georgia
city: Austell
country: United States
facility: WellStar Cobb Hospital
state: Georgia
city: Decatur
country: United States
facility: Charles B. Eberhart Cancer Center at DeKalb Medical Center
state: Georgia
city: Lawrenceville
country: United States
facility: Gwinnett Medical Center
state: Georgia
city: Marietta
country: United States
facility: Kennestone Cancer Center at Wellstar Kennestone Hospital
state: Georgia
city: Riverdale
country: United States
facility: Southern Regional Medical Center
state: Georgia
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: Chanute
country: United States
facility: Cancer Center of Kansas, PA - Chanute
state: Kansas
city: Dodge City
country: United States
facility: Cancer Center of Kansas, PA - Dodge City
state: Kansas
city: El Dorado
country: United States
facility: Cancer Center of Kansas, PA - El Dorado
state: Kansas
city: Kingman
country: United States
facility: Cancer Center of Kansas, PA - Kingman
state: Kansas
city: Liberal
country: United States
facility: Southwest Medical Center
state: Kansas
city: Newton
country: United States
facility: Cancer Center of Kansas, PA - Newton
state: Kansas
city: Parsons
country: United States
facility: Cancer Center of Kansas, PA - Parsons
state: Kansas
city: Pratt
country: United States
facility: Cancer Center of Kansas, PA - Pratt
state: Kansas
city: Salina
country: United States
facility: Cancer Center of Kansas, PA - Salina
state: Kansas
city: Salina
country: United States
facility: Tammy Walker Cancer Center at Salina Regional Health Center
state: Kansas
city: Wellington
country: United States
facility: Cancer Center of Kansas, PA - Wellington
state: Kansas
city: Wichita
country: United States
facility: Associates in Womens Health, PA - North Review
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Medical Arts Tower
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Wichita
state: Kansas
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Wichita
country: United States
facility: Via Christi Cancer Center at Via Christi Regional Medical Center
state: Kansas
city: Wichita
country: United States
facility: Wesley Medical Center
state: Kansas
city: Winfield
country: United States
facility: Cancer Center of Kansas, PA - Winfield
state: Kansas
city: Alexandria
country: United States
facility: Tulane Cancer Center Office of Clinical Research
state: Louisiana
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Billings
country: United States
facility: CCOP - Montana Cancer Consortium
state: Montana
city: Billings
country: United States
facility: Hematology-Oncology Centers of the Northern Rockies - Billings
state: Montana
city: Billings
country: United States
facility: Northern Rockies Radiation Oncology Center
state: Montana
city: Billings
country: United States
facility: St. Vincent Healthcare Cancer Care Services
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: Butte
country: United States
facility: St. James Healthcare Cancer Care
state: Montana
city: Great Falls
country: United States
facility: Frontier Cancer Center
state: Montana
city: Great Falls
country: United States
facility: Great Falls Clinic - Main Facility
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 Medical Oncology at KRMC
state: Montana
city: Kalispell
country: United States
facility: Kalispell Regional Medical Center
state: Montana
city: Missoula
country: United States
facility: Community Medical Center
state: Montana
city: Missoula
country: United States
facility: Guardian Oncology and Center for Wellness
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: 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: Veterans Affairs Medical Center - Dayton
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: Independence
country: United States
facility: Community Oncology Group at Cleveland Clinic Cancer Center
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: Wilmington
country: United States
facility: Clinton Memorial Hospital
state: Ohio
city: Wooster
country: United States
facility: Cleveland Clinic - Wooster
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: 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: Methodist 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: Temple
country: United States
facility: CCOP - Scott and White Hospital
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute at University of Utah
state: Utah
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: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
city: Seattle
country: United States
facility: Minor and James Medical, PLLC
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: Spokane
country: United States
facility: Cancer Care Northwest - Spokane South
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
affiliation: Fred Hutchinson Cancer Center
name: Jerry Radich, MD
role: PRINCIPAL_INVESTIGATOR
References: