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Allogeneic Stem Cell Transplantation Using Mylotarg (CMA-676) Plus Nonmyeloablative Chemotherapy in Older or Medically Infirm Patients With High-Risk Acute Leukemia (ALL), Chronic Myelogenous Leukemia (CML) or Myelodysplastic Syndrome (MDS)

Phase 2/Phase 3
55 Years
75 Years
Not Enrolling

Thank you

Trial Information

Allogeneic Stem Cell Transplantation Using Mylotarg (CMA-676) Plus Nonmyeloablative Chemotherapy in Older or Medically Infirm Patients With High-Risk Acute Leukemia (ALL), Chronic Myelogenous Leukemia (CML) or Myelodysplastic Syndrome (MDS)

Mylotarg is a novel immunoconjugate directed against the CD33 antigen found on most leukemia
cells. This humanized murine IgG4 monoclonal antibody is tagged with the toxin,
calicheamicin. In equal molar concentrations, calicheamicin is about 3200 times more potent
than adriamycin. In a Phase I study involving adult patients with relapse AML, Mylotarg has
been shown to have significant anti-leukemia activity with little toxicity. The most
concerning side effects of Mylotarg were prolonged neutropenia and thrombocytopenia. Phase
II studies have also demonstrated good efficacy with little toxicity.

The goal of this proposal is to include Mylotarg in a nonmyeloablative preparative regimen
similar to FAI used at MD Anderson Cancer Center. The hypothesis is that Mylotarg will
provide potent anti-leukemic effects without adding toxicity to the mini-allogeneic bone
marrow transplant regimen. A more potent anti-leukemic response may increase the complete
remission rates and induce a state of minimal residual disease (MRD). Therefore, the Graft
vs. Leukemia (GVL) effect of allogeneic transplantation will have a better chance for
success. In addition, the administration of donor cells after Mylotarg should ameliorate
the cytopenias previously associated with Mylotarg. This medication likely will be

Patients with high-risk hematopoietic malignancies that express CD33 (i.e. AML, ALL, CML and
MDS) will be included. We will enroll older patients (>55 years old) or medically infirm
patients who are unable to tolerate standard allogeneic bone marrow transplant. Patients
will be evaluated at 28 days post-transplant for evidence of response. Those with residual
disease may be eligible for additional Mylotarg given together with donor lymphocyte
infusions. Additional courses of Mylotarg may improve overall survival in this poor
prognosis group.

Inclusion Criteria:

- Patients 12-75 years of age

- Patients are eligible if deemed ineligible for conventional high dose chemotherapy
programs because of concurrent medical conditions. Patients with refractory AML are
eligible provided ejection fraction >= 35%; FEV1, FVC, or DLCO >= 40%; GPT < 3 x
normal, direct bilirubin < 2.

- Patients must have recovered from previous Grade III-IV toxicity due to prior
antineoplastic therapy (except alopecia).

- Patients with AML with induction failure, relapse or 2nd remission

- Patients with MDS with IPI INT-2 or High-risk disease or CMML.

- Patients with CML in accelerated phase or blast crisis

- Patients with ALL with induction failure, relapse or 2nd remission

- Patients receiving prior BMT are eligible. If myeloablative chemoradiotherapy was
used in the prior transplant patients must be >90 days from transplant. If
non-myeloablative therapy was used patients must be >30 days post-transplant.

- Leukemia cells must express cell surface CD33 evaluated by flow cytometry in > 20% of
leukemia cells.

- Patients must have an HLA identical related donor capable of donating G-CSF
stimulated peripheral blood stem cells using apheresis techniques. If patient has a
contraindication to PBSC collection bone marrow can be used.

- Patients must have a Zubrod PS <2, Cr <2.0, direct bilirubin <2, and transaminases
SGPT <3x normal

- Patients must have an estimated life expectancy > 3 months

- Patient and donor must sign informed consent

Exclusion Criteria:

- no uncontrolled active infection

- no HIV disease

- no pregnancy and no nursing

- no active, uncontrolled CNS leukemia

Type of Study:


Study Design:

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

Outcome Measure:

Maximum Tolerated Dose (MTD) of CMA-676

Outcome Time Frame:

Continual Reassessment Method (CRM); each cycle

Safety Issue:


Principal Investigator

Marcos de Lima, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

May 2001

Completion Date:

November 2004

Related Keywords:

  • Leukemia
  • High Risk Acute Myeloid Leukemia
  • Acute Lymphocytic Leukemia
  • Chronic Myeloid Leukemia
  • Myelodysplastic Syndrome
  • ALL
  • AML
  • MDS
  • CML
  • CMML
  • Nonmyeloablative Preparative Regimen
  • Mylotarg
  • CMA-676
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Myelodysplastic Syndromes
  • Preleukemia



UT MD Anderson Cancer Center Houston, Texas  77030