Bendamustine Hydrochloride, Clofarabine, and Etoposide in Treating Younger Patients With Relapsed or Refractory Hematologic Malignancies

Bendamustine will be combined with clofarabine and etoposide in a five-day cycle.
Dexamethasone will be given to prevent capillary leak syndrome associated with clofarabine.

If the participant does not develop progressive disease or a dose-limiting toxicity (DLT)
during the first cycle, a second cycle may be administered as a bridge to transplant. Each
cycle lasts 21-28 days (or until count recovery).

Concomitant intrathecal therapy can be given at the investigator's discretion, but not on
the same days as chemotherapy. Recommendations are triple intrathecal therapy (methotrexate,
hydrocortisone, cytarabine) weekly for participants with CNS2 or CNS3 disease, and every two
weeks for participants with CNS1 disease. Leucovorin may be given according to institutional
guidelines.

The intent of this study design is for all participants to receive and complete one course
of therapy. Participants who exhibit signs of disease progression or experience an
unacceptable toxicity will be discontinued from protocol treatment.

INCLUSION CRITERIA

- Participants with Hodgkin or Non-Hodgkin lymphoma must meet one of the following
criteria: (a) Relapsing disease in 2nd or greater relapse and measurable disease, or
(b) Refractory disease failing to achieve complete remission (CR) with > 2 induction
or re-induction attempts.

- Participant with acute leukemia must meet one of the following criteria: (a)
Relapsing acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), or acute
biphenotypic leukemia in 2nd or greater relapse; or (b) Refractory ALL, AML, or acute
biphenotypic leukemia failing to achieve CR with ≥ 2 induction or re-induction
attempts.

- Participant with leukemia has M2 or M3 marrow at the time of enrollment. Participant
with M2 marrow must have definite cytogenetic, molecular, or immunophenotypic
evidence of recurrent/refractory disease.

- Age is ≤ 21 years (participant has not yet reached 22nd birthday).

- Karnofsky or Lansky performance score is ≥ 60%. The Lansky performance score should
be used for participants < 16 years and the Karnofsky performance score for
participants ≥ 16 years.

- There are no known contra-indications to any of the planned agents used in this
protocol. Etoposide may be substituted by etoposide phosphate (etopophos) if the
patient has a history of hypersensitivity reaction to etoposide

- Adequate renal function defined as glomerular filtration rate > 60 cc/min/1.73m2, or
normal serum creatinine based on age.

- Adequate hepatic function: (a) Direct bilirubin ≤ upper limit of normal (ULN) for
age, or if total bilirubin is > ULN, direct bilirubin is ≤ 1.4 mg/dl, and (b) AST and
ALT ≤ 5 x ULN for age.

- Adequate cardiac function defined as shortening fraction of ≥ 27% or ejection
fraction ≥ 45%.

- Lymphoma participants without bone marrow involvement must have: (a) Absolute
neutrophil count (ANC) ≥ 1,000/µL, and (b) Platelet count > 50,000/mm^3 (without
transfusion support). [Note: these criteria are waived for participants with leukemia
or lymphoma participants with bone marrow involvement.]

- Participant must have recovered from the acute side effects of all prior anti-cancer
therapy, and :

- At least 2 weeks have elapsed since prior systemic cytotoxic chemotherapy
(except intrathecal chemotherapy, and/or low dose maintenance therapy such as
vincristine, mercaptopurine, methotrexate or glucocorticoids), and

- At least 4 weeks have elapsed since treatment with an investigational agent or
antibody-based therapy, if applicable, and

- If the participant received a prior allogeneic hematopoietic stem cell
transplantation (HSCT), at least 3 months have elapsed and there is no evidence
of active graft-versus-host disease (GVHD), participant has discontinued
immunosuppression, and there is no history of veno-occlusive disease.

EXCLUSION CRITERIA

- Active, uncontrolled infection or severe concurrent medical disease, including but
not limited to congestive heart failure, cardiac arrhythmias, or psychiatric illness.

- Isolated extramedullary disease (leukemia).

- Primary CNS lymphoma.

- Pregnant or lactating (female participant of childbearing potential must have
negative serum or urine pregnancy test required within 7 days prior to start of
treatment).

- Known HIV or active hepatitis B or C infection.

- Known hypersensitivity to bendamustine or mannitol.