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S0910 Epratuzumab, Cytarabine, and Clofarabine in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia

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

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00945815
Enrollment
35
Registered
2009-07-24
Start date
2010-09-30
Completion date
2017-08-31
Last updated
2017-11-06

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

Conditions

Leukemia

Keywords

B-cell adult acute lymphoblastic leukemia, L1 adult acute lymphoblastic leukemia, L2 adult acute lymphoblastic leukemia, recurrent adult acute lymphoblastic leukemia

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).

Interventions

BIOLOGICALepratuzumab
DRUGclofarabine
DRUGcytarabine
OTHERlaboratory biomarker analysis

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 120 Years
Healthy volunteers
No

Inclusion 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)

Design outcomes

Primary

MeasureTime frameDescription
Complete RemissionAfter induction therapy was completed (1 or 2 months)Complete remission (CR) is defined as: \<5% marrow aspirate blasts. Blasts can be \>=5% if the blasts are found to be myeloid and there is no evidence of lymphoblasts by flow cytometry or immunostaining. Neutrophils \>= 1000/mcl; platelets \>100,000/mcl; and no blasts in the peripheral blood. C1 Extramedullary disease status as defined in the protocol. Complete remission with incomplete platelet recovery (CRi) is same as CR but platelet count may be \<=100,000/mcl and/or ANC may be \<1,000/mcl.

Secondary

MeasureTime frameDescription
Number of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsUp to 5 yearsOnly adverse events that are possibly, probably or definitely related to study drug are reported. Any CTCAE 4.0 event of Grade 3 (severe), Grade 4 (life threatening), or Grade 5 (fatal) which were deemed to be related to protocol treatment are included.

Countries

United States

Participant flow

Participants by arm

ArmCount
Ara-C + Clofarabine + Epratuzumab
Ara-C 1 g/m2/d IV Days 1-5, clofarabine 40 mg/m2/d IV Days 2-6, epratuzumab 360 mg/m2/d IV Days 7, 14, 21, 28, acetaminophen 650 mg/d PO Days 7, 14, 21, 28, dephenhydramine 50 mg/d IV Days 7, 14, 21, 28, IT methotrexate 12 mg IT at least 1 wk apart during induction. 1 cycle=28 days. Maximum of one cycle.
31
Total31

Withdrawals & dropouts

PeriodReasonFG000
Overall StudyDeath3
Overall StudyDid not begin protocol therapy1
Overall StudyIneligible3
Overall StudyNot protocol specified1

Baseline characteristics

CharacteristicAra-C + Clofarabine + Epratuzumab
Age, Continuous41 years
Ethnicity (NIH/OMB)
Hispanic or Latino
11 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
18 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
2 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
Race (NIH/OMB)
Asian
1 Participants
Race (NIH/OMB)
Black or African American
1 Participants
Race (NIH/OMB)
More than one race
0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
Race (NIH/OMB)
Unknown or Not Reported
3 Participants
Race (NIH/OMB)
White
26 Participants
Sex: Female, Male
Female
8 Participants
Sex: Female, Male
Male
23 Participants

Adverse events

Event typeEG000
affected / at risk
deaths
Total, all-cause mortality
— / —
other
Total, other adverse events
27 / 31
serious
Total, serious adverse events
15 / 31

Outcome results

Primary

Complete Remission

Complete remission (CR) is defined as: \<5% marrow aspirate blasts. Blasts can be \>=5% if the blasts are found to be myeloid and there is no evidence of lymphoblasts by flow cytometry or immunostaining. Neutrophils \>= 1000/mcl; platelets \>100,000/mcl; and no blasts in the peripheral blood. C1 Extramedullary disease status as defined in the protocol. Complete remission with incomplete platelet recovery (CRi) is same as CR but platelet count may be \<=100,000/mcl and/or ANC may be \<1,000/mcl.

Time frame: After induction therapy was completed (1 or 2 months)

Population: Eligible patients who began protocol therapy.

ArmMeasureValue (NUMBER)
Ara-C + Clofarabine + EpratuzumabComplete Remission52 percentage of participants
Secondary

Number of Patients With Grade 3 Through 5 Treatment-Related Adverse Events

Only adverse events that are possibly, probably or definitely related to study drug are reported. Any CTCAE 4.0 event of Grade 3 (severe), Grade 4 (life threatening), or Grade 5 (fatal) which were deemed to be related to protocol treatment are included.

Time frame: Up to 5 years

Population: Eligible patients who received any treatment and were assessed for toxicity were included in the adverse event summaries.

ArmMeasureGroupValue (NUMBER)
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsAbdominal pain1 Participants
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsAcute kidney injury1 Participants
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsAlanine aminotransferase increased5 Participants
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsAlkaline phosphatase increased1 Participants
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsAnemia6 Participants
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsAnorexia1 Participants
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsAspartate aminotransferase increased6 Participants
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsCardiac arrest2 Participants
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsCatheter related infection2 Participants
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsDiarrhea2 Participants
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsElectrocardiogram QT corrected interval prolonged1 Participants
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsEncephalopathy2 Participants
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsEnterocolitis infectious2 Participants
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsFebrile neutropenia17 Participants
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsGum infection1 Participants
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsHepatic failure1 Participants
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsHypercalcemia1 Participants
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsHyperglycemia1 Participants
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsHyperkalemia1 Participants
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsHypertension1 Participants
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsHypocalcemia1 Participants
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsHypokalemia1 Participants
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsHyponatremia1 Participants
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsHypophosphatemia1 Participants
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsHypotension2 Participants
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsHypoxia2 Participants
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsInfections and infestations-Gram neg. bacteremia1 Participants
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsInvestigations - Bacteremia1 Participants
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsLeukocytosis1 Participants
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsLung infection4 Participants
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsLymphocyte count decreased4 Participants
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsNervous system disorders - subdural hematoma1 Participants
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsNeutrophil count decreased9 Participants
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsOral pain1 Participants
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsPlatelet count decreased12 Participants
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsRespiratory failure1 Participants
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsSepsis4 Participants
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsTooth infection1 Participants
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsTumor lysis syndrome1 Participants
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsTyphlitis2 Participants
Ara-C + Clofarabine + EpratuzumabNumber of Patients With Grade 3 Through 5 Treatment-Related Adverse EventsWhite blood cell decreased8 Participants

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