Gemtuzumab Ozogamicin, Fludarabine, and Total-body Irradiation Followed by Peripheral Stem Cell or Bone Marrow Transplantation in Treating Patients With Advanced Acute Myeloid Leukemia or Myelodysplastic Syndrome

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00008151
First received: January 6, 2001
Last updated: March 31, 2010
Last verified: March 2010
  Purpose

RATIONALE: Monoclonal antibodies such as gemtuzumab ozogamicin can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Peripheral stem cell or bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy and radiation therapy used to kill cancer cells.

PURPOSE: Phase II trial to study the effectiveness of gemtuzumab ozogamicin combined with fludarabine and total-body irradiation followed by donor peripheral stem cell or bone marrow transplantation in treating patients who have advanced acute myeloid leukemia or myelodysplastic syndrome.


Condition Intervention Phase
Leukemia
Myelodysplastic Syndromes
Drug: cyclosporine
Drug: fludarabine phosphate
Drug: gemtuzumab ozogamicin
Drug: methotrexate
Drug: mycophenolate mofetil
Procedure: allogeneic bone marrow transplantation
Procedure: peripheral blood stem cell transplantation
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Gemtuzumab Ozogamicin (GO), Fludarabine, And Low-Dose TBI Followed By Donor Stem Cell Transplantation For Patients With Advanced Acute Myeloid Leukemia Or Myelodysplastic Syndrome

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Study Start Date: October 2000
Study Completion Date: July 2002
Primary Completion Date: July 2002 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES: I. Determine the response and disease-free survival at 1 year of patients with advanced acute myeloid leukemia or myelodysplastic syndrome treated with gemtuzumab ozogamicin, fludarabine, and total body irradiation followed by allogeneic peripheral blood stem cell or bone marrow transplantation with cyclosporine and mycophenolate mofetil. II. Determine the leukemic blast clearance from the blood and marrow in these patients treated with this regimen. III. Determine the safety and pharmacokinetics of gemtuzumab ozogamicin as part of this regimen in these patients. IV. Determine the incidence of donor stem cell engraftment in these patients. V. Determine the incidence and severity of graft-versus-host disease in these patients treated with this regimen. VI. Determine whether donor lymphocyte infusion can be safely used in the patients with mixed or full donor chimerism to eliminate persistent or progressive disease.

OUTLINE: Patients receive gemtuzumab ozogamicin IV over 2 hours on days -21 (first 5 patients) or -14 (subsequent patients) and -7, and fludarabine IV over 2 hours on days -4 to -2. Patients undergo total body irradiation followed by infusion of allogeneic peripheral blood stem cells or bone marrow on day 0. Patients receive oral or IV cyclosporine 2-3 times daily on days -3 to 56 (if related donor) or 100 (if unrelated donor) and oral or IV mycophenolate mofetil twice daily on days 0 to 27 (if related donor) or 40 (if unrelated donor). Patients receive 2 doses of intrathecal methotrexate prior to transplant and an additional 4 doses after transplant. Patients with cerebral spinal fluid (CSF) positive for malignant cells instead receive intrathecal cytarabine, methotrexate and hydrocortisone prior to transplant twice weekly until CSF blasts clear. Patients with persistent or recurrent disease after transplant may receive up to 3 donor lymphocyte infusions if graft-versus-host disease is less than grade II and they have greater than 5% donor CD3 cells. Patients are followed at 6 months and then annually thereafter.

PROJECTED ACCRUAL: A total of 20-40 patients will be accrued for this study within 1-2 years.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS: Diagnosis of recurrent or refractory acute myeloid leukemia CD33 positive Greater than 5% morphologically identified blasts in the marrow OR Diagnosis of myelodysplastic syndrome CD33 positive Greater than 5% morphologically identified blasts in the marrow (refractory anemia with excess blasts (RAEB) and RAEB in transformation) Must have donor who meets the following criteria: HLA-A, B, C, DRB1 and DQB1 identical or mismatched for no more than 1 allelic or cross-reactive antigen Under 75 years of age

PATIENT CHARACTERISTICS: Age: Any age Performance status: Not specified Life expectancy: Not specified Hematopoietic: WBC no greater than 30,000/mm3 (leukophereses or hydroxyurea allowed) Hepatic: Bilirubin no greater than 2 times upper limit of normal No synthetic dysfunction No severe cirrhosis Renal: Not specified Cardiovascular: No symptomatic coronary artery disease No cardiac failure requiring therapy Pulmonary: DLCO at least 35% OR Receiving supplementary continuous oxygen Other: No uncontrolled infection No other diseases that would severely limit life expectancy Not pregnant or nursing Fertile patients must use effective contraception during and for 1 year after study

PRIOR CONCURRENT THERAPY: No post-transplant growth factors during and for 1 month after mycophenolate mofetil administration

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00008151

Locations
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109-1024
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Study Chair: Eric Sievers, MD Fred Hutchinson Cancer Research Center
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00008151     History of Changes
Other Study ID Numbers: 1555.00, FHCRC-1555.00, NCI-G00-1900, CDR0000068383+
Study First Received: January 6, 2001
Last Updated: March 31, 2010
Health Authority: United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Fred Hutchinson Cancer Research Center:
recurrent childhood acute myeloid leukemia
recurrent adult acute myeloid leukemia
refractory anemia with excess blasts
refractory anemia with excess blasts in transformation
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
childhood myelodysplastic syndromes

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Cyclosporins
Cyclosporine
Methotrexate
Mycophenolic Acid
Mycophenolate mofetil
Fludarabine monophosphate
Vidarabine
Fludarabine
Gemtuzumab
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on April 16, 2014