Combination Chemotherapy Followed by Bone Marrow Transplantation in Treating Patients With Advanced Hematologic Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00014469
First received: April 10, 2001
Last updated: March 6, 2013
Last verified: March 2013
  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:


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

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
Investigators
Study Chair: Trudy N. Small, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

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)

Additional relevant MeSH terms:
Neoplasms
Graft vs Host Disease
Leukemia
Myelodysplastic Syndromes
Preleukemia
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Immune System Diseases
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Busulfan
Melphalan
Methotrexate
Tacrolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Antimetabolites, Antineoplastic

ClinicalTrials.gov processed this record on July 22, 2014