Clinical trial NCT00004896: Busulfan and Cyclophosphamide Followed by Bone Marrow Transplantation in Treating Patients With Acute Myelogenous Leukemia or Myelodysplastic Syndrome
Official title: Phase II Study of High-Dose Busulfan and Cyclophosphamide Followed by Allogeneic Bone Marrow Transplantation for Patients With Acute Myelogenous Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Diseases
Keywords: recurrent adult acute myeloid leukemia
adult acute myeloid leukemia in remission
adult acute erythroid leukemia (M6)
adult acute myeloblastic leukemia without maturation (M1)
adult acute myeloblastic leukemia with maturation (M2)
adult acute promyelocytic leukemia (M3)
adult acute myelomonocytic leukemia (M4)
adult acute monoblastic leukemia (M5a)
adult acute megakaryoblastic leukemia (M7)
refractory anemia
refractory anemia with ringed sideroblasts
refractory anemia with excess blasts
refractory anemia with excess blasts in transformation
chronic myelomonocytic leukemia
adult acute monocytic leukemia (M5b)
previously treated myelodysplastic syndromes
myelodysplastic/myeloproliferative disease, unclassifiable
atypical chronic myeloid leukemia
adult acute myeloid leukemia with t(8;21)(q22;q22)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with t(15;17)(q22;q12)
childhood myelodysplastic syndromes
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 16
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with donor bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of busulfan and cyclophosphamide followed by bone marrow transplantation in treating patients who have acute myelogenous leukemia or myelodysplastic syndrome.

Detailed description: OBJECTIVES:

* Determine the remission duration, disease-free survival, and overall survival of patients with acute myelogenous leukemia in remission or early relapse or myelodysplastic syndrome treated with high-dose busulfan and cyclophosphamide followed by allogeneic bone marrow transplantation.

OUTLINE: Patients receive oral high-dose busulfan every 6 hours for 14-16 doses on days -9 to -6, followed by high-dose cyclophosphamide IV over 1 hour on days -5 to -2. Allogeneic bone marrow is infused on day 0.

Patients who have already had 1 transplant receive high-dose cyclophosphamide IV on days -6 and -5, total body irradiation twice a day on days -4 to -1, and allogeneic bone marrow infusion on day 0.

All patients receive prophylaxis for graft versus host disease.

Patients are followed every 6 months for at least 2 years.

PROJECTED ACCRUAL: A total of 25-40 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Morphologically proven (from bone marrow aspirate smears or touch preps of marrow biopsy) acute myelogenous leukemia or myelodysplastic syndrome of 1 of the following subtypes:

  * Acute myeloblastic leukemia (M1, M2)
  * Acute promyelocytic leukemia (M3)
  * Acute myelomonocytic leukemia (M4)
  * Acute monocytic leukemia (M5)
  * Acute erythroleukemia (M6)
  * Acute megakaryocytic leukemia (M7)
  * Refractory anemia
  * Refractory anemia with excess blasts
  * Refractory anemia with excess blasts in transformation
  * Refractory anemia with ringed sideroblasts
  * Chronic myelomonocytic leukemia
* In remission or in early relapse as defined by less than 20% blast cells in the marrow or overt active acute myeloid leukemia
* Suitable marrow donor, defined as a sibling donor matched at the HLA-A, HLA-B, and HLA-D/DR locus nonreactive in bidirectional mixed lymphocyte culture or a donor who is mismatched at 1 antigen loci
* Active CNS disease allowed

PATIENT CHARACTERISTICS:

Age:

* 16 to physiologic 60

Performance status:

* ECOG 0-2

Life expectancy:

* Not specified

Hematopoietic:

* Not specified

Hepatic:

* Bilirubin no greater than 3 times upper limit of normal (ULN) unless due to Gilbert's disease
* SGOT no greater than 3 times ULN

Renal:

* Creatinine no greater than 2.0 mg/dL

Cardiovascular:

* Cardiac ejection fraction normal

Pulmonary:

* FEV_1 at least 50% of predicted
* DLCO at least 50% of predicted

Other:

* HIV negative
* No evidence of persistent infection
* No concurrent organ damage or medical problems that would preclude study therapy

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* Not specified

Endocrine therapy:

* Not specified

Radiotherapy:

* Not specified

Surgery:

* Not specified

Other:

* No concurrent antibiotics

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
Study officials:
affiliation: Robert H. Lurie Cancer Center
name: Martin S. Tallman, MD
role: STUDY_CHAIR
References: