Location: New Programs :101614
|Diagnosis Region||Lymphoid Leukemia|
|Trial Type||Treatment (TRE)|
|Title||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 (ALL)|
|Primary Investigator||Robert Stuart firstname.lastname@example.org|
|Study Coordinator||Rachel Whirley 843-792-9579 email@example.com|
Each of the criteria in the following section must be met in order for a patient to be considered eligible for
registration. Use the spaces provided to confirm a patient's eligibility. For each criterion requiring test
results and dates, please record this information on the Prestudy Form (Form #43884) and submit to the
Data Operations Center in Seattle (see Section 14.0). Any potential eligibility issues should be addressed
to the Data Operations Center in Seattle at 206/652-2267 prior to registration.
In calculating days of tests and measurements, the day a test or measurement is done is considered Day
0. Therefore, if a test is done on a Monday, the Monday 4 weeks later would be considered Day 28. This
allows for efficient patient scheduling without exceeding the guidelines. If Day 14, 28 or 42 falls on a
weekend or holiday, the limit may be extended to the next working day.
5.1. Patients must have a prior morphologic diagnosis of precursor B cell acute lymphoblastic
leukemia (ALL) (non T-cell), as defined in Section 4.1b and be either refractory to a
standard induction regimen or have relapsed following successful prior induction therapy.
Patients may have had any number of prior therapies. Patients with M0 AML or mixed
lineage leukemia are not eligible for this study. Patients with L3 (Burkitts) are also not
1. A standard induction regimen is defined as any program of treatment that
includes vincristine and prednisone or high dose cytarabine/mitoxantrone.
2. Patients who have received any number of inductions or achieved any number of
remissions are eligible.
5.2 Patients must have a diagnosis of Philadelphia chromosome-negative ALL. Patients with
unknown Ph status by cytogenetics or FISH and unknown BCR/ABL status by PCR are
eligible for registration, but must be removed from protocol therapy if found to be Ph+ or
BCR/ABL+ after registration.
5.3 Patients must have evidence of ALL in their marrow or peripheral blood.
1. For ALL in 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). Appropriate marker studies including CD19 (B cell), CD10, CD5,
and CD7 (T cell) must be performed. Co-expression of myeloid antigens (CD13
and CD33) will not exclude patients. If possible, the lineage specific markers
cytoplasmic CD79a (B cells), cytoplasmic CD3 (T cells) and cytoplasmic MPO
(myeloid cells) should be determined. The blood/bone marrow sample for these
assays must be obtained within 14 days before registration.
2. Patients with only extramedullary disease in the absence of bone marrow or
blood involvement are not eligible.
5.4 Patients must have at least 5% lymphoblasts present in the blood or bone marrow
collected within 14 days prior to registration.
5.5 At least 20% of marrow and/or peripheral blood lymphoblasts must be CD22+ (≥ 20
percent) by flow cytometry from a sample collected within 14 days prior to registration.
5.6 Pretreatment cytogenetics must be performed on all patients. Collection of pretreatment
specimens must be completed within 14 days prior to registration to S0910. Specimens
must be submitted to the site’s preferred cytogenetics laboratory.
5.7 Patients must be offered participation in minimal residual disease testing. With the
patient’s consent, specimens collected within 14 days prior to registration must be
submitted as outlined in Section 15.3.
5.8 Patients must not have active CNS involvement (by clinical evaluation). Patients with
previous documented history of CNS involvement of ALL, or with clinical signs or
symptoms consistent with CNS involvement of ALL, must have a lumbar puncture which
is negative for CNS involvement of ALL. The lumbar puncture must be completed within
14 days prior to registration. Patients with no previous history of documented CNS
involvement and with no clinical signs or symptoms consistent with CNS involvement are
not required to have completed a lumbar puncture before registration. Note that
monitoring of CNS involvement and treatment with intrathecal therapy is recommended
during protocol treatment.
5.9 Patients may have received prior allogeneic or autologous bone marrow transplant.
However, patients who have received prior transplant (allogeneic or autologous) will not
be eligible if they are still receiving immunosuppression therapy for the treatment of
GvHD. Patients with prior allogeneic bone marrow transplant will be eligible only if both
of the following conditions are met:
1. The transplant must have been performed more than 90 days before registration
to this study, and
2. At the time of registration the patient must not have ≥ Grade 2 acute graft versus
host disease (GvHD) or either moderate or severe limited chronic GvHD, or
extensive chronic GvHD of any severity.
5.10 Patients must not have received chemotherapy, any other investigational agents, or have
undergone any major surgery within 14 days prior to registration, with the following
• hydroxyurea, which may be administered concurrently with study drug until the
white blood count has come down to a reasonable level (as deemed by the
• Maintenance therapy with steroids, vincristine and/or anti-metabolite agents,
such as but not limited to, mercaptopurine, thioguanine and methotrexate.
All drug-related toxicities must have resolved to ≤ Grade 2.
5.11 Patients must be ≥ 16 years of age. (Institutions must assess their local requirements for
obtaining consent for treating minors on this protocol prior to registering a minor.)
5.12 Patients < 22 years of age must be willing to receive prophylactic intrathecal
chemotherapy (administered per Section 7.3) while on study.
5.13 Patients must not have received previous treatment with clofarabine or epratuzumab
5.14 Patients must have a Zubrod Performance Status of 0-2 (see Section 10.10).
5.15 Patients must have a serum creatinine ≤ 1.0 mg/dl
If serum creatinine > 1.0 mg/dL, then the estimated glomerular filtration rate (GFR) must
be > 60 mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease
Predicted GFR (ml/min/1.73 m2) = 186 x (Serum Creatinine)-1.154 x (age in years)-0.023
x (0.742 if patient is female) x (1.212 if patient is African American).
All tests to establish serum creatinine or glomerular filtration rate must be obtained within
14 days prior to registration.
5.16 Patients must have SGOT (AST) and SGPT (ALT) ≤ 2.5 x Institutional Upper Limit of
Normal (IULN) obtained within 14 days prior to registration.
5.17 Patients must have a pretreatment bilirubin ≤ 1.5 x Institutional Upper Limit of Normal
(IULN) obtained within 14 days prior to registration.
5.18 Patients must have alkaline phosphatase ≤ 2.5 x Institutional Upper Limit of Normal
(IULN) obtained within 14 days prior to registration.
5.19 Patients must undergo triplicate EKG within 14 days prior to registration. Electrolytes (K
and Mg) should be corrected prior to the first EKG. For QTc > 500, the Study
Coordinator must be contacted to determine whether the patient will be eligible. Note
that triplicate EKG is required at other timepoints as outlined in Section 7.3.
5.20 Patients must not have a systemic fungal, bacterial, viral, or other infection that is not
controlled (defined as exhibiting ongoing signs/symptoms related to the infection and
without improvement, despite appropriate antibiotics or other treatment).
5.21 Patients must not have ≥ Grade 2 neuropathy (cranial, motor or sensory) within 14 days
prior to registration.
5.22 Patients known to be positive for HIV (the human immunodeficiency virus) may be
eligible, but must be discussed with and approved by the Study Coordinator prior to
registration (see Section 2.0 for justification).
HIV+ patients meeting the following criteria should be considered as potentially eligible
for the study provided there are no other features present that would pose undue risk to
a. No history of AIDS-defining conditions
b. CD4 cells > 350 cells/mm3
c. If on antiretroviral agents, must not include zidovudine or stavudine
d. Must be willing to take prophylaxis for pneumocystis jirovecii pneumonia (PCP)
during protocol therapy regardless of CD4 cell count and until the CD4 cells are >
200/mm3 following completion of treatment.
5.23 Patients must not be pregnant or nursing because of the teratogenic potential of the drug
used in this study. Women/men of reproductive potential must have agreed to use an
effective contraceptive method during the study and for a minimum of six months after
5.24 Prior malignancy other than ALL is allowed, provided it is in remission and there is no
plan to treat the prior malignancy at the time of registration.
5.25 All patients must be informed of the investigational nature of this study and must sign and
give written consent in accordance with institutional and federal guidelines.
5.26 At the time of patient registration, the treating institution's name and ID number must be
provided to the Statistical Center in order to ensure that the current (within 365 days)
date of institutional review board approval for this study has been entered into the data
|Hypothesis||To test whether the complete remission rate (CR + CRi) in patients with relapsed or refractory precursor B-cell acute lymphoblastic leukemia (ALL) is sufficiently high following treatment with cytarabine, clofarabine, and epratuzumab to warrant further investigation.|
|Available Documents|| HIPAA |