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

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ClinicalTrials.gov Identifier: NCT00134017
Recruitment Status : Completed
First Posted : August 24, 2005
Results First Posted : August 31, 2018
Last Update Posted : August 31, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary:

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 or disease Intervention/treatment Phase
Chronic Myeloproliferative Disorders Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Drug: Busulfan Drug: Cyclophosphamide Phase 2

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 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 142 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (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
Actual Study Start Date : June 2004
Actual Primary Completion Date : February 2010
Actual Study Completion Date : February 2010


Arm Intervention/treatment
Experimental: Bone marrow transplant
Myeloablative bone marrow transplant with a busulfan (Bu), cyclophosphamide (Cy), preparative regimen and post-transplant cyclophosphamide (PTCy) as GVHD prophylaxis
Drug: Busulfan
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

Drug: Cyclophosphamide
Days -3, -2, +3, +4: 50 mg/kg IV daily
Other Names:
  • Cytoxan
  • CTX




Primary Outcome Measures :
  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 Outcome Measures :
  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.



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Ages Eligible for Study:   6 Months to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00134017


Locations
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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 at Johns Hopkins
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Leo Luznik, MD Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Publications of Results:
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Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT00134017    
Other Study ID Numbers: J0373
P01CA015396 ( U.S. NIH Grant/Contract )
P30CA006973 ( U.S. NIH Grant/Contract )
NA_00034100 ( Other Identifier: JHMIRB )
First Posted: August 24, 2005    Key Record Dates
Results First Posted: August 31, 2018
Last Update Posted: August 31, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Product Manufactured in and Exported from the U.S.: No
Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
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:
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Lymphoma
Leukemia
Multiple Myeloma
Neoplasms, Plasma Cell
Preleukemia
Myelodysplastic Syndromes
Myeloproliferative Disorders
Syndrome
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Disease
Pathologic Processes
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Bone Marrow Diseases
Precancerous Conditions
Cyclophosphamide
Busulfan
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs