Combination Chemotherapy, Tacrolimus, and Mycophenolate Mofetil in Treating Patients Who Are Undergoing a Donor Bone Marrow Transplant For Hematologic Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00134017
First received: August 22, 2005
Last updated: March 20, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Chronic Myeloproliferative Disorders
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Drug: busulfan
Drug: cyclophosphamide
Drug: mycophenolate mofetil
Drug: tacrolimus
Procedure: allogeneic bone marrow transplantation
Procedure: bone marrow ablation with stem cell support
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: HLA Matched Related and Unrelated Bone Marrow Transplantation With Busulfan/Cyclophosphamide and Post Transplantation Cyclophosphamide for Hematological Malignancies

Resource links provided by NLM:

Genetic and Rare Diseases Information Center resources: Lymphosarcoma Lymphoma, Small Cleaved-cell, Diffuse Leukemia, Myeloid Chronic Myeloid Leukemia Myelodysplastic Syndromes Acute Lymphoblastic Leukemia Multiple Myeloma Chronic Myeloproliferative Disorders Hodgkin Lymphoma Acute Myelocytic Leukemia Acute Non Lymphoblastic Leukemia Acute Myeloid Leukemia, Adult Follicular Lymphoma Hodgkin Lymphoma, Childhood B-cell Lymphomas Myelofibrosis Burkitt Lymphoma Lymphoma, Large-cell Lymphoma, Large-cell, Immunoblastic Plasmablastic Lymphoma Lymphoblastic Lymphoma Small Non-cleaved Cell Lymphoma Chronic Lymphocytic Leukemia Leukemia, B-cell, Chronic Chronic Myelomonocytic Leukemia Acute Lymphoblastic Leukemia, Childhood Chronic Neutrophilic Leukemia Hypereosinophilic Syndrome Acute Myeloid Leukemia, Childhood Mantle Cell Lymphoma Anaplastic Plasmacytoma
U.S. FDA Resources

Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • Dose Finding [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]

    To find the optimal dose of post-grafting immunosuppression with high-dose cyclophosphamide (Cy), FK-506 and MMF following myeloablative fully HLA-matched related or unrelated BMT for the patients with hematological malignancies who are at high risk of relapse.

    To estimate the incidence and severity of acute GVHD and other toxicities following myeloablative fully HLA-matched related or unrelated BMT using this approach for the patients with hematological malignancies



Secondary Outcome Measures:
  • Immune reconstitution and disease control [ Time Frame: Survival ] [ Designated as safety issue: No ]

    To evaluate immune reconstitution following HLA-matched related or unrelated myeloablative BMT and post-grafting immunossuppression with high dose Cy, FK-506 and MMF.

    To evaluate disease control after myeloablative fully HLA-matched related or unrelated BMT for the patients with hematological malignancies who are at high risk of relapse when Cy is included in the post-grafting immune suppression



Enrollment: 92
Study Start Date: May 2004
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Detailed Description:

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 1 of the following immunosuppressive treatment regimens:

    • Regimen 1: Patients receive high-dose cyclophosphamide IV over 1 hour on day 3.
    • Regimen 2: Patients receive high-dose cyclophosphamide IV over 1 hour on days 3 and 4.
    • Regimen 3: Patients receive high-dose cyclophosphamide as in regimen 2 and oral mycophenolate mofetil three times daily on days 5-35.
    • Regimen 4: Patients receive high-dose cyclophosphamide as in regimen 2 and mycophenolate mofetil as in regimen 3. Patients also receive tacrolimus IV or orally twice daily on days 5-50.

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

PROJECTED ACCRUAL: Approximately 30-60 patients (approximately 5 per immunosuppressive treatment regimen) will be accrued for this study.

  Eligibility

Ages Eligible for Study:   up to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  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: NCT00134017

Locations
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Investigators
Principal Investigator: Leo Luznik, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00134017     History of Changes
Other Study ID Numbers: CDR0000440164, J0373, P01CA015396, P30CA006973, JHOC-03121504, JHOC-J0373
Study First Received: August 22, 2005
Last Updated: March 20, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
adult acute myeloid leukemia in remission
refractory anemia with excess blasts
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
childhood acute myeloid leukemia in remission
recurrent adult acute myeloid leukemia
recurrent childhood acute myeloid leukemia
secondary acute myeloid leukemia
de novo myelodysplastic syndromes
adult acute lymphoblastic leukemia in remission
childhood acute lymphoblastic leukemia in remission
recurrent adult acute lymphoblastic leukemia
recurrent childhood acute lymphoblastic leukemia
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
childhood chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
relapsing chronic myelogenous leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
chronic eosinophilic leukemia
chronic idiopathic myelofibrosis
chronic neutrophilic leukemia
stage III adult Hodgkin lymphoma
stage IV adult Hodgkin lymphoma
stage II multiple myeloma
stage III multiple myeloma

Additional relevant MeSH terms:
Neoplasms
Leukemia
Lymphoma
Lymphoma, Non-Hodgkin
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Myelodysplastic Syndromes
Preleukemia
Myeloproliferative Disorders
Lymphoma, Large-Cell, Immunoblastic
Hematologic Neoplasms
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Bone Marrow Diseases
Precancerous Conditions
Neoplasms by Site
Busulfan
Cyclophosphamide
Mycophenolate mofetil

ClinicalTrials.gov processed this record on August 20, 2014