Clinical trial NCT00014469: Combination Chemotherapy Followed by Bone Marrow Transplantation in Treating Patients With Advanced Hematologic Cancer
Official title: A Phase II Trial of IV Busulfan (Busulfex) and Melphalan as a Preparatory Regimen Prior to Allogeneic Bone Marrow Transplantation for the Treatment of Advanced and High Risk Hematologic Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Graft Versus Host Disease
Leukemia
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Neoplasms
Keywords: recurrent childhood acute lymphoblastic leukemia
recurrent childhood acute myeloid leukemia
recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
relapsing chronic myelogenous leukemia
refractory chronic lymphocytic leukemia
chronic phase chronic myelogenous leukemia
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
adult acute myeloid leukemia in remission
adult acute lymphoblastic leukemia in remission
childhood acute myeloid leukemia in remission
childhood acute lymphoblastic leukemia in remission
refractory anemia with excess blasts
refractory anemia with excess blasts in transformation
chronic myelomonocytic leukemia
acute undifferentiated leukemia
secondary acute myeloid leukemia
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
graft versus host disease
refractory cytopenia with multilineage dysplasia
juvenile myelomonocytic leukemia
childhood chronic myelogenous leukemia
atypical chronic myeloid leukemia, BCR-ABL1 negative
myelodysplastic/myeloproliferative neoplasm, unclassifiable
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)
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_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 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 melphalan followed by donor bone marrow transplantation in treating patients who have advanced hematologic cancer.

Detailed description: OBJECTIVES:

* Determine the antileukemic potential of busulfan and melphalan prior to allogeneic bone marrow transplantation in patients with advanced or high-risk hematologic malignancy.
* Determine the incidence of transplantation-related morbidity and mortality in patients treated with this regimen.
* Determine the incidence of acute and chronic graft-versus-host disease in patients treated with this regimen.

OUTLINE: Patients receive cytoreductive chemotherapy comprising busulfan IV over 2 hours every 6 hours for a total of 16 doses on days -8 to -5 and melphalan IV over 30 minutes on days -4 to -2. Patients undergo T-cell replete allogeneic bone marrow transplantation on day 0. For graft-versus-host disease prophylaxis, patients receive tacrolimus IV continuously or every 12 hours beginning on day -1 and continuing for 50 days to 6 months followed by a taper. Once oral medications are tolerated, patients switch to oral tacrolimus every 12 hours. Patients also receive methotrexate IV on days 1, 3, 6, and 11.

Patients are followed weekly through day 100, every 6 weeks for 3 months, every 3 months for 1 year, and then every 3-6 months for 6 months.

PROJECTED ACCRUAL: A maximum of 30 patients will be accrued for this study within 3 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of one of the following:

  * Infant leukemia
  * Acute lymphoblastic leukemia in 3rd or greater remission or relapse
  * Undifferentiated or biphenotypic leukemia in 2nd or greater remission or relapse
  * Juvenile chronic myelogenous leukemia (CML)
  * Acute myelogenous leukemia (AML) in 3rd or greater remission or relapse
  * Primary advanced myelodysplastic syndrome (MDS) excluding refractory anemia (RA) and RA with ringed sideroblasts
  * Therapy-related MDS of any stage or AML
  * CML in 2nd or greater chronic phase, accelerated, or blastic phase
  * Acute leukemia, CML, or MDS but unable to tolerate total body irradiation (TBI) due to potential neurotoxicity (prior TBI, prior local radiotherapy,or under 2 years of age)
* No active CNS disease
* Related or unrelated bone marrow donor matched at HLA-A, B, and DR beta 1

PATIENT CHARACTERISTICS:

Age:

* Under 60 (over 60 considered on case-by-case basis)

Performance status:

* Karnofsky 70-100%
* Lansky 70-100%

Life expectancy:

* Not specified

Hematopoietic:

* Not specified

Hepatic:

* AST and ALT less than 2 times upper limit of normal
* Bilirubin less than 1.5 mg/dL unless liver is involved with disease

Renal:

* Creatinine normal
* Creatinine clearance greater than 60 mL/min

Cardiovascular:

* Asymptomatic with no prior risk factors OR
* LVEF greater than 50% if symptomatic

Pulmonary:

* Asymptomatic with no prior risk factors OR
* Diffusion capacity greater than 50% predicted (corrected for hemoglobin) if symptomatic

Other:

* No active uncontrolled viral, bacterial, or fungal infection
* Not pregnant or nursing
* Negative pregnancy test
* HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* More than 6 months since prior allogeneic or autologous stem cell transplantation

Chemotherapy:

* Not specified

Endocrine therapy:

* Not specified

Radiotherapy:

* See Disease Characteristics

Surgery:

* Not specified

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Trudy N. Small, MD
role: STUDY_CHAIR
References: