Phase I/II Study of the Combination of Inotuzumab Ozogamycin (CMC-544) with Low-intensity Chemotherapy in Patients with Acute Lymphoblastic Leukemia (ALL)
If you are reading and signing this form on behalf of a potential participant, please note: Any time the words "you," "your," "I," or "me" appear, it is meant to apply to the potential participant. The goal of the Phase I part of this clinical research study is to test 2 dose levels of the drug inotuzumab ozogamycin to find the highest tolerable dose that can be given in combination with chemotherapy. The goal of Phase II is to learn if inotuzumab ozogamycin given in combination with chemotherapy can help to control acute lymphoblastic leukemia (ALL). The safety of the study drugs will also be studied. Participants in this study are at least 60 years of age and have newly diagnosed ALL or have refractory-relapsed ALL regardless of age. Inotuzumab ozogamycin is designed to attach to a protein that is often found in leukemia cells. This may cause the cancer cells to die. Rituximab is designed to attach to cancer cells and damage them, which may cause the cells to die. Hyper-CVD includes a combination of cyclophosphamide, vincristine, dexamethasone, methotrexate, Ara-C (cytarabine), and Neulasta (pegfilgrastim). The maintenance therapy used in this study is called POMP, which includes a combination of mercaptopurine, methotrexate, vincristine, and prednisone. These chemotherapy drugs are designed to interfere with the multiplication of cancer cells, which may slow or stop their growth and spread throughout the body. This may cause the cancer cells to die.
Disease Group: Leukemia
Treatment Agent: 6-mercaptopurine
Treatment Location: Only at MDACC
Phase I: Determine the maximum tolerated dose (MTD) of inotuzumab ozogamycin in combination with low-intensity chemotherapy in elderly patients (age 60 or older) with ALL. Phase II: a. Evaluate the efficacy of inotuzumab ozogamycin in combination with low-intensity chemotherapy in elderly patients with ALL. To evaluate the side effects of the treatment. b. Evaluate the regimen efficacy in refractory-relapsed ALL. Primary Study Endpoint a. Phase I: Define the dose limiting toxicities (DLTs) and MTD. b. Phase II: Evaluate progression-free survival (PFS) ) in frontline elderly ALL. c. Evaluate response rate and survival in refractory-relapsed ALL.
IRB Review and Approval Date: 08/26/2011
Recruitment Status: Open
Projected Accrual: N/A
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 </= 1.95 mg/dL and SGPT or SGOT </= 3 x upper limit 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 </= 2.6 mg/dL and creatinine </= 3 mg/dL.
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.
1) Ph-positive ALL, Burkitt’s Leukemia or Lymphoma, T-cell ALL or
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.