Combination Chemotherapy Followed by Bone Marrow Transplantation in Treating Patients With Advanced Hematologic Cancer - Full Text View

Purpose

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.

Condition	Intervention	Phase
Graft Versus Host Disease Leukemia Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Neoplasms	Drug: busulfan Drug: melphalan Drug: methotrexate Drug: tacrolimus Procedure: allogeneic bone marrow transplantation	Phase 2


Study Type:	Interventional
Study Design:	Primary Purpose: Treatment
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

Resource links provided by NLM:

Genetics Home Reference related topics: chronic myeloid leukemia cytogenetically normal acute myeloid leukemia familial acute myeloid leukemia with mutated CEBPA

MedlinePlus related topics: Bone Marrow Transplantation Cancer Leukemia Myelodysplastic Syndromes

Drug Information available for: Busulfan Methotrexate Melphalan Melphalan hydrochloride Tacrolimus

Genetic and Rare Diseases Information Center resources: Myeloid Leukemia Acute Myeloid Leukemia Acute Non Lymphoblastic Leukemia Myelodysplastic Syndromes Chronic Lymphocytic Leukemia Leukemia, B-cell, Chronic Homologous Wasting Disease Chronic Myeloid Leukemia Acute Lymphoblastic Leukemia Chronic Myelomonocytic Leukemia Childhood Acute Lymphoblastic Leukemia Chronic Myeloproliferative Disorders Myelodysplastic/myeloproliferative Disease Juvenile Myelomonocytic Leukemia

U.S. FDA Resources

Further study details as provided by Memorial Sloan Kettering Cancer Center:


Study Start Date:	December 2000
Study Completion Date:	May 2007
Primary Completion Date:	May 2007 (Final data collection date for primary outcome measure)

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


Ages Eligible for Study:	Child, Adult, Senior
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00014469

Locations


United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021

Sponsors and Collaborators

Memorial Sloan Kettering Cancer Center

National Cancer Institute (NCI)

Investigators


Study Chair:	Trudy N. Small, MD	Memorial Sloan Kettering Cancer Center

More Information


ClinicalTrials.gov Identifier:	NCT00014469 History of Changes
Other Study ID Numbers:	00-126 P30CA008748 P01CA023766 MSKCC-00126 NCI-H01-0070
Study First Received:	April 10, 2001
Last Updated:	March 6, 2013
Health Authority:	United States: Federal Government

Keywords provided by Memorial Sloan Kettering Cancer Center:


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)

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)

Additional relevant MeSH terms:


Leukemia Syndrome Myelodysplastic Syndromes Preleukemia Graft vs Host Disease Myeloproliferative Disorders Myelodysplastic-Myeloproliferative Diseases Neoplasms by Histologic Type Neoplasms Disease Pathologic Processes Bone Marrow Diseases Hematologic Diseases Precancerous Conditions Immune System Diseases	Methotrexate Tacrolimus Busulfan Melphalan Abortifacient Agents, Nonsteroidal Abortifacient Agents Reproductive Control Agents Physiological Effects of Drugs Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Dermatologic Agents Enzyme Inhibitors Folic Acid Antagonists

ClinicalTrials.gov processed this record on September 30, 2016