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Completed

NCT Number: NCT00134017

Combination Chemotherapy, Bone Marrow Transplant, and Post Transplant Cyclophosphamide for Hematologic Cancer

RATIONALE: Giving chemotherapy before a donor bone marrow transplant helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclophosphamide, mycophenolate mofetil, or tacrolimus after transplant may stop this from happening.

PURPOSE: This clinical trial is studying how well giving combination chemotherapy together with tacrolimus and mycophenolate mofetil works in treating patients who are undergoing a donor bone marrow transplant for hematologic cancer.

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Key information

Conditions

Chronic Myeloproliferative Disorders Anemia Anemia, Refractory Anemia, Refractory, with Excess of Blasts Blast Crisis Blood Protein Disorders Bone Marrow Diseases Burkitt Lymphoma Carcinogenesis Cardiovascular Diseases Cell Transformation, Neoplastic Chronic Disease Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities DNA Virus Infections Dendritic Cell Sarcoma, Interdigitating Disease Attributes Epstein-Barr Virus Infections Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhagic Disorders Hemostatic Disorders Herpesviridae Infections Histiocytic Disorders, Malignant Histiocytosis Hodgkin Disease Immune System Diseases Immunoproliferative Disorders Infections Leukemia Leukemia, B-Cell Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Lymphoid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Myeloid Leukemia, Myeloid, Accelerated Phase Leukemia, Myeloid, Acute Leukemia, Myeloid, Chronic-Phase Leukemia, Myelomonocytic, Chronic Leukemia, Neutrophilic, Chronic Lymphatic Diseases Lymphoma Lymphoma, B-Cell Lymphoma, B-Cell, Marginal Zone Lymphoma, Follicular Lymphoma, Large B-Cell, Diffuse Lymphoma, Large-Cell, Immunoblastic Lymphoma, Mantle-Cell Lymphoma, Non-Hodgkin Lymphoproliferative Disorders Multiple Myeloma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic-Myeloproliferative Diseases Myeloproliferative Disorders Neoplasms Neoplasms by Histologic Type Neoplasms, Plasma Cell Neoplastic Processes Paraproteinemias Pathologic Processes Pathological Conditions, Signs and Symptoms Pdgfra-Associated Chronic Eosinophilic Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Primary Myelofibrosis Recurrence Tumor Virus Infections Vascular Diseases Virus Diseases

Age range

6 month–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231-2410, United States

About this study

OBJECTIVES:

Primary

  • Determine the optimal dose of post-transplant immunosuppression comprising high-dose cyclophosphamide, tacrolimus, and mycophenolate mofetil administered after myeloablative conditioning chemotherapy comprising busulfan and cyclophosphamide followed by allogeneic bone marrow transplantation in patients with high-risk hematologic malignancies.
  • Determine the incidence and severity of acute graft-versus-host disease in patients treated with this regimen.
  • Determine other toxic effects of this regimen in these patients.

Secondary

  • Determine immune reconstitution in patients treated with this regimen.
  • Determine disease control in patients treated with this regimen.

OUTLINE: This is a pilot study. Patients are stratified according to age (≤ 19 years old vs > 19 years old).

  • Myeloablative conditioning chemotherapy: Patients receive busulfan IV or orally 4 times daily on days -7 to -4 OR days -6 to -3 and cyclophosphamide IV over 1 hour once daily on days -3 to -1 OR days -2 and -1.
  • Allogeneic bone marrow transplantation: Patients undergo allogeneic bone marrow transplantation on day 0.
  • Immunosuppression therapy: Patients receive high-dose cyclophosphamide IV over 1 hour on days 3 and 4.

After completion of study transplantation, patients are followed at 30 and 60 days, 6 months, 1 year, and then annually thereafter.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

DISEASE CHARACTERISTICS:

  • Diagnosis of 1 of the following hematologic malignancies:
  • Acute myeloid leukemia (AML), meeting 1 of the following criteria:
  • AML beyond first complete remission (CR1)
  • Refractory AML
  • AML arising from myelodysplastic syndromes (MDS)
  • Secondary AML
  • MDS
  • Refractory anemia with excess blasts with > 10% blasts in bone marrow
  • Acute lymphoblastic leukemia (ALL), meeting 1 of the following criteria:
  • ALL in CR1 with 1 of the following high-risk features:
  • Philadelphia chromosome (Ph)-positive disease
  • Less than 1 year of age at diagnosis
  • Cytogenetic abnormalities involving chromosome 11q23
  • ALL beyond CR1
  • Refractory ALL
  • Chronic myeloid leukemia beyond first chronic phase
  • Chronic myelomonocytic leukemia
  • Chronic lymphocytic leukemia
  • Stage III-IV disease
  • Does not meet criteria for other bone marrow transplantation (BMT) studies
  • Myeloproliferative disorders
  • Ph-negative disease
  • Hodgkin's or non-Hodgkin's lymphoma
  • Chemotherapy-resistant disease
  • Paroxysmal nocturnal hemoglobinuria with life-threatening thrombosis
  • Multiple myeloma
  • Stage II or III disease
  • Very high-risk disease
  • Having an unrelated donor is considered a high-risk condition
  • Meets medical criteria for myeloablative BMT for the Sidney Kimmel Comprehensive Cancer Center
  • Bone marrow donor available, meeting 1 of the following criteria:
  • Genotypically HLA-identical sibling
  • Phenotypically matched first-degree relative
  • Unrelated donor molecularly matched at HLA-A, -B, -C, -DRB1, and -DQB1

PATIENT CHARACTERISTICS:

Age

  • 6 months to 65 years

Performance status

  • Not specified

Life expectancy

  • Not specified

Hematopoietic

  • See Disease Characteristics

Hepatic

  • Not specified

Renal

  • Not specified

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • See Disease Characteristics

Endocrine therapy

  • No concurrent dexamethasone as an antiemetic during immunosuppression therapy

Radiotherapy

  • Not specified

Surgery

  • Not specified

Other

  • No concurrent immunosuppressants until ≥ 24 hours after the completion of cyclophosphamide (post-transplantation)

Treatment and study plan

busulfan

Drug

Days -7 to -4: 4 mg/kg PO daily OR 3.2 mg/kg IV daily OR 160 mg/m^2 daily (for pediatric recipients)

Other names: Myleran, Busulfex

Cyclophosphamide

Drug

Days -3, -2, +3, +4: 50 mg/kg IV daily

Other names: Cytoxan, CTX

Primary outcomes

  1. Percentage of Participants Who Develop Acute Graft-versus-host Disease (GVHD)

    Time frame: Day 100

    Percentage of participants who developed grades II-IV and grades III-IV acute GVHD. Acute GVHD is defined by the Przepiorka criteria, which stages the degree of organ involvement in the skin, liver, and gastrointestinal (GI) tract, based on severity, with Stage 1+ being least severe and stage 4+ being the most severe. Grading of acute GVHD is as follows: Grade I (skin involvement stages 1+ to 2+, with no liver or GI involvement), Grade II (skin involvement stages 1+ to 3+, liver 1+, GI tract 1+), Grade III (skin involvement stages 2+ to 3+, liver 1+, GI tract 2+ to 4+), Grade IV (skin involvement stages 4+, Liver 4+).

Secondary outcomes

  1. Days to Engraftment

    Time frame: Up to one year

    Median number of days to neutrophil and platelet engraftment.

  2. Chimerism

    Time frame: Day 30, Day 60

    Number of patients who achieved 100% donor chimerism.

  3. Non-relapse Mortality

    Time frame: Day 100, 2 years

    Percentage of participants who died for BMT-related reasons.

  4. Relapse

    Time frame: 2 years

    Percentage of participants who developed relapse or progressive disease.

Sponsors and collaborators

Lead sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Other

Collaborators

  • National Cancer Institute (NCI)

Registry information

Official study title

HLA Matched Related and Unrelated Bone Marrow Transplantation With Busulfan/Cyclophosphamide and Post Transplantation Cyclophosphamide for Hematological Malignancies

Important dates

Study start
2004
Primary completion
2010
Study completion
2010
First posted
Aug 24, 2005
Registry last updated
Aug 31, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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