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Phase I/II Evaluation of Safety and Activity of Mylotarg Plus Melphalan and Fludarabine as Preparative Therapy for Older or Medically Infirm Patients Undergoing Allogeneic Bone Marrow and Peripheral Blood Stem Cell Transplantation

Phase 1/Phase 2
12 Years
75 Years
Not Enrolling
Acute Myelogenous Leukemia, Myelodysplastic Syndrome, Chronic Lymphocytic Leukemia

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Trial Information

Phase I/II Evaluation of Safety and Activity of Mylotarg Plus Melphalan and Fludarabine as Preparative Therapy for Older or Medically Infirm Patients Undergoing Allogeneic Bone Marrow and Peripheral Blood Stem Cell Transplantation

Before treatment starts, patients will have a complete physical exam, including blood and
urine tests. Patients will have a chest x-ray, heart scan, lung function test, and a bone
marrow biopsy. Women who are able to have children will have a pregnancy test.

In this study, patients will receive Mylotarg twelve days before the transplant. The first
patients will receive Mylotarg at the lowest dose level. As the study continues, the dose
levels will be increased as long as no severe side effects occur. Mylotarg may be given in
the outpatient Ambulatory Treatment Center (ATC). Patients will be monitored in the ATC for
eight hours on the day of infusion. For the next 5 days, patients will be evaluated in the
Clinic on a daily basis or as per physician orders. One week before the transplant, all
patients will be admitted to the hospital and will continue their treatment as inpatients.
Patients experiencing side effects from their leukemia or leukemia treatment may need to be
hospitalized earlier.

On the 1st day of hospitalization, patients will receive fluids by vein. On the 5th, 4th,
3rd and 2nd day before the transplant, patients will receive Fludarabine, by vein.
Melphalan will be given by vein on the 2nd day before transplant. Patients receiving five
out of six antigen matched or unrelated bone marrow will also receive antithymocyte
globulin, by vein, on the 3rd, 2nd and 1st day before transplant.

On the 7th day, healthy blood stem cells or bone marrow from the donor will be given through
the central catheter. Some donor bone marrow or stem cells may be saved for future

Patients will also receive several other medications to help the treatment work and to help
prevent infections while their immune system is weak. Tacrolimus and methotrexate will be
given to prevent graft-versus-host disease (GVHD). GVHD occurs when the donor's immune cells
fight the patient's body. The Tacrolimus will be started on the day before the transplant
and will continue for up to six months. Tacrolimus is given by vein at first and then by
mouth when patients are able to eat. Methotrexate is given by vein on days 1, 3, 6 and
possibly on day 11 after the transplant.

Sulfamethoxazole (Bactrim) or pentamidine will be given to fight bacteria. Bactrim is given
by mouth when the counts are good. Pentamidine is given by vein when the counts are low.
Acyclovir will be given at first by vein and then Valtrex will be given by pill to prevent
viral infections. Granulocyte colony-stimulating factor (G-CSF) will be given to help the
new bone marrow grow. It is given as an injection under the skin beginning on the 7th day
after the transplant. It will continue until the patient's white blood cells reach an
acceptable level. Overall, some of these drugs will be given for as long as 6 months or
possibly longer. Other medications may be necessary. If you are allergic to some of these
drugs, changes will be made.

Patients will be in the hospital for about 3-4 weeks. Patients will have checkups every day
until discharged from the hospital then 3 times a week until their blood counts improve.
Patients will then be seen by their doctor at least every week until 100 days after the bone
marrow transplant. Patients must stay in Houston during this time. After 100 days, patients
will return at least every 3 months for the first year, then every 6 months for an
additional two years.

Bone marrow samples will be taken at about 1 month, 3 months, 6 and 12 months after the

This is an investigational study. All of the drugs in this study are approved by the FDA.
About 47 patients will take part in this study. All will be enrolled at M. D. Anderson.

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
always eligible if ejection fraction > 35, FEV1, FVC, or DLCO > 40%, abnormal LFT's.

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

- Patients with the following disease categories will be eligible:

1. AML with induction failure, relapse or 2nd remission

2. MDS with IPI INT-2 or High-risk disease (Appendix 4) or CMML

3. CML in accelerated phase or blast crisis

4. Interferon or STI resistant CML not eligible for conventional stem cell

- 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-compatible related donor (6/6 or 5/6 HLA-match) capable of
donating bone marrow or G-CSF stimulated peripheral blood stem cells using aphereses
techniques or a 6/6 HLA matched unrelated bone marrow donor (serologic matching for
Class I, molecular matching for DR?1).

- Patients must have a ECOG PS<2 (Appendix 6), Cr<2.0, bilirubin <2, and (SGPT) <3x

- Patients must have an estimated life expectancy > 3 months

- Patient and donor must sign informed consent. Unrelated donors will be consented
according to the National Donor Marrow Registry policy

Exclusion Criteria:

- uncontrolled active infection

- HIV disease

- pregnancy and nursing

- 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 Mylotarg as Determined by Number of Participants With Dose Limiting Toxicity (DLT) at Each Dose Level

Outcome Time Frame:

Followed in outpatient clinic from day -12 (prior to transplant) thru day -6 with each dose level

Safety Issue:


Principal Investigator

Marcos De Lima, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

May 2001

Completion Date:

October 2006

Related Keywords:

  • Acute Myelogenous Leukemia
  • Myelodysplastic Syndrome
  • Chronic Lymphocytic Leukemia
  • Acute Myelogenous leukemia
  • AML
  • Myelodysplastic Syndrome
  • MDS
  • Chronic Lymphocytic Leukemia
  • CML
  • Mylotarg
  • Gemtuzumab
  • Gemtuzumab ozogamicin
  • Melphalan
  • Alkeran
  • Fludarabine Phosphate
  • Fludarabine
  • Fludara
  • Anti-thymocyte globulin
  • ATG
  • Allogeneic Bone Marrow
  • Peripheral Blood Stem Cell Transplantation
  • Allo PBSCT
  • Allogeneic transplantation
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Myelodysplastic Syndromes
  • Preleukemia



MD Anderson Cancer Center Houston, Texas  77030-4096