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

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

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00337168
Enrollment
36
Registered
2006-06-15
Start date
2006-10-31
Completion date
2013-01-31
Last updated
2015-03-25

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

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

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.

Interventions

DRUGclofarabine

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

DRUGcytarabine

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

Sponsors

National Cancer Institute (NCI)
CollaboratorNIH
SWOG Cancer Research Network
Lead SponsorNETWORK

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No

Inclusion 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

Design outcomes

Primary

MeasureTime frameDescription
Number of Patients With Complete RemissionBetween day 28 and day 35 inclusiveComplete 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

MeasureTime frameDescription
Expression of Nucleoside TransportersOn average, two weeks before treatment startedExpression 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 CytogeneticsOn average, 2 weeks before treatment started
ToxicityPatients were assess for adverse events after each induction cycle (up to two cycles) and after the one consolidation cycleNumber of patients with Grade 3-5 adverse events that are related to study drug by given type of adverse event

Countries

United States

Participant flow

Participants by arm

ArmCount
Induction36
Total36

Withdrawals & dropouts

PeriodReasonFG000
Overall StudyDeath5
Overall StudyDid not start therapy1
Overall StudyNot protocol specified2

Baseline characteristics

CharacteristicInduction
Age, Continuous41 years
Region of Enrollment
United States
36 participants
Sex: Female, Male
Female
13 Participants
Sex: Female, Male
Male
23 Participants

Adverse events

Event typeEG000
affected / at risk
deaths
Total, all-cause mortality
— / —
other
Total, other adverse events
31 / 36
serious
Total, serious adverse events
5 / 36

Outcome results

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

Time frame: Between day 28 and day 35 inclusive

Population: Eligible patients who started therapy

ArmMeasureValue (NUMBER)
InductionNumber of Patients With Complete Remission3 participants
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+.

Time frame: On average, two weeks before treatment started

Population: Eligible patients who submitted paraffin-embedded tissue

ArmMeasureGroupValue (NUMBER)
InductionExpression of Nucleoside TransportersHigh expression of hENT17 participants
InductionExpression of Nucleoside TransportersHigh expression of hCNT36 participants
InductionExpression of Nucleoside TransportersHigh expression of dCK cytoplasmic4 participants
InductionExpression of Nucleoside TransportersHigh expression of dCK nuclear4 participants
Secondary

Number of Patients With Very Poor Risk Cytogenetics

Time frame: On average, 2 weeks before treatment started

Population: Eligible patients with acceptable centrally reviewed cytogenetics

ArmMeasureValue (NUMBER)
InductionNumber of Patients With Very Poor Risk Cytogenetics10 participants
Secondary

Toxicity

Number of patients with Grade 3-5 adverse events that are related to study drug by given type of adverse event

Time frame: Patients were assess for adverse events after each induction cycle (up to two cycles) and after the one consolidation cycle

Population: Eligible patients who started therapy

ArmMeasureGroupValue (NUMBER)
InductionToxicityHypoxia1 Participants with a given type of AE
InductionToxicityINR1 Participants with a given type of AE
InductionToxicityALT, SGPT (serum glutamic pyruvic transaminase)5 Participants with a given type of AE
InductionToxicityAST, SGOT (serum glut oxaloacetic transaminase)7 Participants with a given type of AE
InductionToxicityAlbumin, serum-low (hypoalbuminemia)3 Participants with a given type of AE
InductionToxicityAnorexia1 Participants with a given type of AE
InductionToxicityAscites (non-malignant)2 Participants with a given type of AE
InductionToxicityBilirubin (hyperbilirubinemia)3 Participants with a given type of AE
InductionToxicityCalcium, serum-low (hypocalcemia)1 Participants with a given type of AE
InductionToxicityColitis1 Participants with a given type of AE
InductionToxicityColitis, infectious (e.g., Clostridium difficile)2 Participants with a given type of AE
InductionToxicityConfusion1 Participants with a given type of AE
InductionToxicityCreatinine4 Participants with a given type of AE
InductionToxicityDIC (disseminated intravascular coagulation)1 Participants with a given type of AE
InductionToxicityDeath not assoc with CTCAE term-Multi-organ fail1 Participants with a given type of AE
InductionToxicityDermatology/Skin-Other (Specify)1 Participants with a given type of AE
InductionToxicityDiarrhea2 Participants with a given type of AE
InductionToxicityDyspnea (shortness of breath)1 Participants with a given type of AE
InductionToxicityEdema: limb1 Participants with a given type of AE
InductionToxicityFatigue (asthenia, lethargy, malaise)2 Participants with a given type of AE
InductionToxicityFebrile neutropenia14 Participants with a given type of AE
InductionToxicityGlucose, serum-high (hyperglycemia)1 Participants with a given type of AE
InductionToxicityHemoglobin13 Participants with a given type of AE
InductionToxicityHypotension3 Participants with a given type of AE
InductionToxicityInfec with Gr 3\4 neutrophils - Bladder (urin1 Participants with a given type of AE
InductionToxicityIInfec with Gr 3\4 neutrophils - Blood9 Participants with a given type of AE
InductionToxicityInfec with Gr 3\4 neutrophils - Catheter-rela1 Participants with a given type of AE
InductionToxicityInfec with Gr 3\4 neutrophils - Colon2 Participants with a given type of AE
InductionToxicityInfec with Gr 3\4 neutrophils - Conjunctiva1 Participants with a given type of AE
InductionToxicityInfec with Gr 3\4 neutrophils - Larynx1 Participants with a given type of AE
InductionToxicityInfec with Gr 3\4 neutrophils - Lung (pneumon2 Participants with a given type of AE
InductionToxicityInfec with Gr 3\4 neutrophils - Skin (celluli1 Participants with a given type of AE
InductionToxicityInfec with Gr 3\4 neutrophils - Urinary tract1 Participants with a given type of AE
InductionToxicityInfec with Gr 3\4 neutrophils - Wound1 Participants with a given type of AE
InductionToxicityInfection with unknown ANC - Lung (pneumonia)1 Participants with a given type of AE
InductionToxicityInfection-Other (Specify)1 Participants with a given type of AE
InductionToxicityLeukocytes (total WBC)11 Participants with a given type of AE
InductionToxicityLiver dysfunction/failure (clinical)1 Participants with a given type of AE
InductionToxicityLymphopenia7 Participants with a given type of AE
InductionToxicityMental status1 Participants with a given type of AE
InductionToxicityNeutrophils/granulocytes (ANC/AGC)18 Participants with a given type of AE
InductionToxicityPTT (Partial thromboplastin time)1 Participants with a given type of AE
InductionToxicityPain - Abdomen NOS1 Participants with a given type of AE
InductionToxicityPain - Back1 Participants with a given type of AE
InductionToxicityPain - Bone1 Participants with a given type of AE
InductionToxicityPlatelets20 Participants with a given type of AE
InductionToxicityPneumonitis/pulmonary infiltrates1 Participants with a given type of AE
InductionToxicityPotassium, serum-high (hyperkalemia)1 Participants with a given type of AE
InductionToxicityPotassium, serum-low (hypokalemia)4 Participants with a given type of AE
InductionToxicityPruritus/itching1 Participants with a given type of AE
InductionToxicityRenal failure3 Participants with a given type of AE
InductionToxicityRestrictive cardiomyopathy1 Participants with a given type of AE
InductionToxicitySodium, serum-high (hypernatremia)1 Participants with a given type of AE
InductionToxicitySodium, serum-low (hyponatremia)2 Participants with a given type of AE
InductionToxicitySupraventricular and nodal arrhythmia1 Participants with a given type of AE
InductionToxicityTumor lysis syndrome1 Participants with a given type of AE
InductionToxicityTyphlitis (cecal inflammation)1 Participants with a given type of AE
InductionToxicityUric acid, serum-high (hyperuricemia)1 Participants with a given type of AE
InductionToxicityPleural effusion (non-malignant)1 Participants with a given type of AE

Source: ClinicalTrials.gov · Data processed: Feb 24, 2026