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Phase I/II Study of the Combination of Inotuzumab Ozogamycin (CMC-544) With Low-intensity Chemotherapy in Elderly Patients With Acute Lymphoblastic Leukemia (ALL)


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
Leukemia, Acute Lymphoblastic Leukemia

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Trial Information

Phase I/II Study of the Combination of Inotuzumab Ozogamycin (CMC-544) With Low-intensity Chemotherapy in Elderly Patients With Acute Lymphoblastic Leukemia (ALL)


Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a study
group based on when you join this study. One (1) group of 6 participants will be enrolled
in the Phase I portion of the study, and 1 group of up to 60 participants will be enrolled
in Phase II.

The Phase I group will receive the lowest dose level of inotuzumab ozogamycin. The Phase II
group will receive a higher dose of inotuzumab ozogamycin, if no intolerable side effects
were seen.

All participants will receive the same dose level of the rest of the study drugs.

Study Drug Administration:

You will receive up to 8 cycles of induction and consolidation therapy. Each study cycle is
about 3-4 weeks.

Hyper-CVAD: Cycles 1, 3, 5, and 7 On Days 1-3 of Cycles 1, 3, 5, and 7, you will receive
cyclophosphamide 2 times a day by vein over about 3 hours.

On Days 1-3 of Cycles 1, 3, 5, and 7, you will receive mesna as a continuous infusion
starting about 1 hour before you receive cyclophosphamide and ending about 12 hours after
the last dose of cyclophosphamide. Mesna is given to lower the risk of side effects.

On Days 1 and 8 of Cycles 1, 3, 5, and 7 (+/- 2 days), you will receive vincristine by vein
over about 30 minutes.

On Days 1-4 and 11-14 of Cycles 1, 3, 5, and 7 (+/- 2 days), you will take dexamethasone by
mouth 1 time a day.

On Days 2 and 8 of Cycles 1 and 3 (+/- 2 days), if your doctor feels it is in your best
interest, you may receive rituximab over 6-8 hours (Day 2 of Cycle 1) or over 2-6 hours (all
other days).

On Day 3 of Cycle 1 and Day 2 or 3 of Cycle 3 (+/- 2 days), you will receive inotuzumab
ozogamycin by vein over about 60 minutes (+/- 15 minutes). The dose you receive will depend
on when you start treatment. If your doctor thinks it is needed to lower the risk of side
effects, you will take acetaminophen, diphenhydramine, and hydrocortisone before your doses
of inotuzumab ozogamycin. Acetaminophen will be given by mouth or by vein over 15-30
minutes. Diphenhydramine will be given by mouth or by vein over 15-30 minutes.
Hydrocortisone will be given by vein over 15-30 minutes.

You will also receive methotrexate alternating with cytarabine by a spinal tap
(intrathecally) to help lower the risk of the disease coming back in the fluid surrounding
your brain. A spinal tap (also called a lumbar puncture) is when fluid surrounding the
spinal cord is removed by inserting a needle into the lower back. The affected area is
numbed with local anesthetic during the procedure. It can also be used to give
chemotherapy.

On Day 2 of Cycles 1, 2, 3, and 4 (+/- 2 days), you will receive intrathecal methotrexate.

On Day 8 of Cycles 1, 2, 3, and 4 (+/- 2 days), you will receive intrathecal cytarabine.

On Day 4 of Cycles 1, 3, 5, and 7 (+/- 2 days) you will receive pegfilgrastim as an
injection under the skin.

Methotrexate alternating with cytarabine by vein: Cycles 2, 4, 6, and 8 On Day 1 of Cycles
2, 4, 6 and 8, you will receive methotrexate by vein over about 24 hours (+/- 3 hours).

On Days 2 and 3 of Cycles 2, 4, 6, and 8 you will receive cytarabine by vein 2 times a day
over about 3 hours each time.

On Days 2 and 8 of Cycles 2 and 4 (+/- 2 days), if your doctor feels it is in your best
interest, you may receive rituximab by vein over about 2-6 hours.

On Day 2 or 3 of Cycles 2 and 4 (+/- 2 days), you will receive inotuzumab ozogamycin by vein
over about 60 minutes (+/- 15 minutes). If your doctor thinks it is in your best interest,
you may receive inotuzumab ozogamycin more often.

On Day 4 of Cycles 2, 4, 6, and 8 (+/- 2 days), you will receive pegfilgrastim as an
injection under the skin.

On Days 2-5 of Cycles 2, 4, 6, and 8 you will receive leucovorin by vein over about 1 hour
or by mouth every 6 hours for 8 doses beginning about 12 hours (+/- 2 hours) after you
finish receiving methotrexate. Leucovorin is given to lower the risk of side effects.

Your dose of the study drugs may change depending on any side effects you may have.

You may be given other drugs to help prevent side effects. Your doctor will tell you about
these drugs, how they will be given, and the possible risks.

Maintenance Therapy:

After you complete the first 8 cycles described above, you will receive POMP maintenance
therapy for up to 3 years.

You will take mercaptopurine by mouth 2 times a day for 3 years.

You will take methotrexate by mouth 1 time a week for 3 years.

You will receive vincristine by vein over about 30 minutes 1 time a month for 1 year.

You will take prednisone by mouth 1 time a day for 5 days every month for 1 year.

If bone marrow samples drawn during consolidation and maintenance therapy show that the
disease is not gone, your doctor may recommend that you receive additional doses of
inotuzumab ozogamycin. You would receive it at a lower dose 1 time every 3-4 weeks for up
to 6 doses instead of receiving the POMP maintenance therapy.

Study Visits:

Within 1 week before Day 1 of each cycle:

- You will have a physical exam, including measurement of your vital signs.

- Your performance status will be recorded.

- You will be asked how you are feeling and about any drugs you may be taking.

- If the doctor thinks it is needed, blood (about 1 tablespoon) will be drawn to test how
the study drugs may affect cancer cells.

- If you are receiving rituximab and if you have a history of irregular heartbeat or
chest pain due to heart trouble, you will have ECGs performed before the rituximab
infusion, 1 time during the infusion, and within 2 hours after the infusion. The
rituximab infusion will be stopped if you have any serious episodes of irregular
heartbeat.

- If you are receiving rituximab, you may be checked during the physical exam for any
signs or symptoms of intestinal blockage and/or holes. If your doctor thinks it is
needed, you will have CT scans and/or you will meet with a surgeon.

Blood (about 1 tablespoon) will be drawn for routine tests 1-3 times each week during Cycles
1 and 2, at least 1 time every week during consolidation, and every 2-4 weeks during
maintenance cycles.

You will have a bone marrow aspiration and/or biopsy (about 1 teaspoon) to check the status
of the disease between Days 14-21 (+/- 3 days) of Cycle 1, and then every 2-4 cycles during
consolidation.

Within 1 week before Day 1 of Cycles 2, 4, 6, and 8, you will have a chest x-ray to check
your lungs.

Every 3 months during maintenance:

- You will be asked how you are feeling and about any drugs you may be taking.

- You will have a bone marrow aspiration and/or biopsy (about 1 teaspoon). Bone marrow
aspirations and/or biopsies may be done every 3-6 months beginning in the 2nd year of
maintenance.

The blood draws for routine tests, bone marrow aspirations/biopsies, and ECGs may be
repeated more often anytime the doctor thinks it is needed.

Length of Treatment:

You may receive the study drugs for up to 8 cycles (about 8 months) and then maintenance
therapy for up to 3 years. You will no longer be able to take the study drugs if the
disease gets worse, if intolerable side effects occur, or if you are unable to follow study
directions.

Your participation on the study will be over once you have completed the follow-up.

Follow-up:

You will have a follow-up visit 30 days after your last dose of the study drugs. At this
visit, you will be asked about any side effects you may be having. If you cannot make it to
the clinic for this visit, it can be done over the phone with a member of the study staff.
The phone call should last about 10 minutes.

This is an investigational study. Rituximab, Hyper-CVAD, methotrexate, cytarabine, and POMP
maintenance drugs are FDA approved and commercially available for the treatment of leukemia.
Combining inotuzumab ozogamycin with rituximab is investigational. Giving inotuzumab
ozogamycin to patients with leukemia is investigational.

Up to 106 patients will take part in this study. All will be enrolled at MD Anderson.


Inclusion Criteria:



1. Patients age 60 years or older with previously untreated ALL of pre-B, Philadelphia
chromosome (Ph-) negative ALL. Minimal prior therapy (less than 1 week of steroids,
vincristine, and/or 1 dose of anthracycline or alkylating agents) are allowed.

2. Zubrod performance status 0-3.

3. Adequate liver function (bilirubin of normal [ULN], unless considered due to tumor), and renal function (creatinine 2 mg/dL). Even if organ function abnormalities are considered due to tumor, the upper
limit for bilirubin is
4. Provision of written informed consent.

5. Patients in first remission are eligible.

6. Patients with refractory-relapsed ALL of any age are eligible, provided they are not
eligible for regimens of higher priority. Currently study 2012-0151 (inotuzumab vs.
intensive chemotherapy in ALL salvage 1 and 2) is an FDA pivotal trial and is a
higher priority (September 10, 2012).

Exclusion Criteria:

1. Ph-positive ALL, Burkitt's Leukemia or Lymphoma, T-cell ALL or lymphoblastic
lymphoma.

2. Patient with active heart disease (NYHA class >/= 3 as assessed by history and
physical examination).

3. Patients with a cardiac ejection fraction (as measured by either MUGA or
echocardiogram) < 40% are excluded.

4. Patients with active hepatitis are excluded.

5. Pregnant or breast-feeding women are excluded.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Phase I: Maximum Tolerated Dose (MTD) of Inotuzumab Ozogamycin in Combination With Low-Intensity Chemotherapy

Outcome Description:

MTD defined by Dose Limiting Toxicities (DLTs) where DLTS observed in less than 2/6 participants treated at dose level 1 results in testing dose level 2 of inotuzumab ozogamycin. If DLTs are observed in < 2/6 patients treated, the second dose level is utilized for Phase II.

Outcome Time Frame:

With each 4 week study cycle

Safety Issue:

Yes

Principal Investigator

Hagop Kantarjian, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

2010-0991

NCT ID:

NCT01371630

Start Date:

August 2011

Completion Date:

Related Keywords:

  • Leukemia
  • Acute Lymphoblastic Leukemia
  • Leukemia
  • Acute Lymphoblastic Leukemia
  • ALL
  • Elderly
  • pre-B, Philadelphia chromosome (Ph-) negative
  • Maximum tolerated dose
  • Inotuzumab Ozogamycin
  • CMC-544
  • Vincristine
  • Rituximab
  • Rituxan
  • Cyclophosphamide
  • Cytoxan
  • Neosar
  • Dexamethasone
  • Decadron
  • Mesna
  • Mesnex
  • Pegfilgrastim
  • Neulasta
  • PEG-G-CSF
  • Methotrexate
  • Ara-C
  • Cytarabine
  • Cytosar
  • DepoCyt
  • Cytosine Arabinosine Hydrochloride
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030