Study of Clofarabine, Etoposide, Cyclophosphamide [CEC], Liposomal Vincristine (VCR), Dexamethasone and Bortezomib in Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) and Lymphoblastic Lymphoma (LL)

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a study
part based on when you join this study. At least 1 group of up to 6 participants is planned
to be enrolled in the safety lead-in part of the study, and up to 54 participants will be
enrolled in Part 2. If the doctor thinks it is needed, more groups may be enrolled in the
safety lead-in part of the study.

If you are enrolled in the safety lead-in, the dose level of clofarabine, etoposide,
cyclophosphamide, liposomal vincristine, and bortezomib will depend on when you join the
study. If there are no intolerable side effects after the first 6 participants, Phase 2 will
open for all future participants. If intolerable side effects were seen, 6 more participants
will be enrolled in the safety lead-in and will receive a lower dose of the drug combination
than the group before them. This will continue until the highest tolerable dose of the drug
combination is found.

If you are enrolled in Part 2, you will receive the drug combination at the highest dose that
was tolerated in the safety lead-in.

All participants will receive the same dose level of dexamethasone or rituximab/ofatumumab.

Study Drug Administration:

Each cycle is about 28 days.

You will receive the study drugs in induction and consolidation phases. Induction therapy is
designed to help control the disease. If at any point during the induction phase the disease
appears to be responding to treatment (this is called remission), you will begin the
consolidation phase. Consolidation therapies are designed to keep the disease in remission.

Induction and/or Reinduction (Cycles 1-2):

- You will receive clofarabine by vein over about 1-2 hours on Days 1-5.

- You will receive etoposide by vein over about 2 hours on Days 1-5, after you receive
clofarabine.

- You will receive cyclophosphamide by vein over about 1 hour on Days 1-5 about 4 hours
after you receive clofarabine.

- You will receive liposomal vincristine by vein over about 1 hour on Days 2 and 11.

- You will receive dexamethasone by mouth or by vein over about 15 minutes on Days 1-5.
The study doctor will determine how you receive the drug.

- You will receive bortezomib as an injection under the skin on Days 1, 4, 8, and 11.

- You will receive either ofatumumab or rituximab by vein over about 4-24 hours on Days 2
and 11. The amount of time that this dose will take depends on how you tolerate the
drug.

- You will receive pegfilgrastim as an injection under the skin on Day 6.

Depending on how the disease responds to induction treatment, you may receive a 2nd induction
course (reinduction) or begin consolidation treatment. If you need to receive reinduction,
this will be given in 1 additional cycle.

Consolidation (5 Cycles: Cycles 2-6 or 3-7):

- You will receive clofarabine by vein over about 1-2 hours on Days 1-4.

- You will receive etoposide by vein over about 2 hours on Days 1-4, after you receive
clofarabine.

- You will receive cyclophosphamide by vein over about 1 hour on Days 1-4 about 4 hours
after you receive clofarabine.

- You will receive liposomal vincristine by vein over about 1 hour on Days 2 and 11.

- You will receive dexamethasone by mouth or by vein over about 15 minutes on Days 1-5.

- You will receive bortezomib as an injection under the skin on Days 1, 4, 8, and 11.

- You will receive pegfilgrastim as an injection under the skin on Day 6.

- If the doctor thinks it is needed, you will receive either ofatumumab or rituximab by
vein over about 4-24 hours on Days 2 and 11 of your first 4 cycles of consolidation
(Cycles 2-5 or 3-6).

If the doctor thinks it is needed, you may be given other chemotherapy, such as a tyrosine
kinase inhibitor (TKI) or other intrathecal chemotherapy (such as methotrexate or cytarabine)
to help prevent central-nervous-system leukemia. Intrathecal chemotherapy is given by
injecting the chemotherapy directly into the cerebrospinal fluid by use of a lumbar
puncture/spinal tap or Ommaya reservoir. The study doctor and separate consents will explain
TKI therapy and intrathecal chemotherapy to you in more detail, including the type of
chemotherapy you will receive and its risks.

If the doctor thinks it is needed, you may also be given standard drugs (such as rasburicase
or ondansetron) to help decrease the risk of side effects. You may ask the study staff for
information about how the drugs are given and their risks.

If you cannot come to the hospital for the therapy, you may be able to receive the study
drug(s) at a doctor's clinic closer to your home.

Length of Study:

You may continue taking the study drugs for as long as the study doctor thinks it is in your
best interest. You will no longer be able to take the study drugs if the disease gets worse
or comes back during treatment, if intolerable side effects occur, or if you are unable to
follow the study directions.

Study Visits:

One (1) time each week during Cycles 1-6, blood (about 1-2 teaspoons) will be drawn for
routine tests.

If your doctor thinks it is needed, on Days 14 (+/- 3 days) and 28 (+/- 5 days) of Cycle 1,
you will have a bone marrow aspirate to check the status of the disease. This will then be
done every 2 weeks unless the disease appears to respond to treatment.

If your doctor thinks it is needed, at any time during the study you may have a chest x-ray
or CT scan of the chest.

Inclusion Criteria:

1. Relapsed and/or refractory Philadelphia negative acute lymphoblastic leukemia or
lymphoblastic lymphoma (Lead-in and Phase 2)

2. Relapsed and/or refractory Philadelphia positive acute lymphoblastic leukemia, Burkitt
leukemia/lymphoma or "double-hit" leukemia/lymphoma (2 separate cohorts, phase II
only)

3. At least 21 days elapsed from prior systemic chemotherapy (at least 14 days elapsed
from prior systemic chemotherapy in the setting of rapidly progressive disease without
significant residual extramedullary toxicity). Hydroxyurea and dexamethasone permitted
up to approximately 24 hours prior to the start of therapy. Interruption of TKI not
required in Ph positive ALL subset.

4. ECOG performance status of rapidly proliferative/refractory ALL who would benefit from this regimen. We don't
want to exclude such patients who may derive benefit from this salvage regimen).

5. Serum bilirubin exception for Gilbert's syndrome

6. Estimated creatinine clearance or GFR (glomerular filtration rate) >/= 50 mL/min

7. Signed informed consent

Exclusion Criteria:

1. Active >/= grade 3 peripheral neuropathy

2. Active hepatic graft-versus-host disease

3. Known positivity for Hepatitis B or C

4. Pregnancy

5. Breast feeding after pregnant