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Trial record 51 of 52 for:    "Acute Leukemia" | "Anti-Bacterial Agents"

Reduced-intensity, Related-donor Bone Marrow Transplantation Followed by High-dose Cyclophosphamide for Hematologic Cancers

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ClinicalTrials.gov Identifier: NCT01135329
Recruitment Status : Terminated (The stopping rule was met and hence the study was closed)
First Posted : June 2, 2010
Results First Posted : July 3, 2018
Last Update Posted : July 3, 2018
Sponsor:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary:

This research is being done to learn more about reduced-intensity bone marrow transplantation (BMT), also known as a "mini" transplant for patients with blood cancers, using bone marrow from a relative.

The main goal of the study is to determine how quickly the donor's bone marrow "takes" in your body. Other goals include describing how many people accept the bone marrow and how quickly the blood counts come up; describing Graft-versus-host disease (GVHD) and other complications; and describing how many people survive without progressive cancer and survive overall


Condition or disease Intervention/treatment Phase
Lymphoma Leukemia Myelodysplastic Syndrome Drug: Fludarabine Drug: Busulfan Drug: Cyclophosphamide Drug: Mycophenolate Mofetil Drug: Tacrolimus Phase 2

Detailed Description:

At the present time there are few or no cures for people with cancer of the blood or lymph glands outside of a bone marrow transplant (BMT). BMT has developed over several decades of research as an effective treatment of various malignant and nonmalignant hematologic diseases.

This research is being done to learn more about reduced-intensity bone marrow transplantation (BMT), also known as a "mini" transplant for patients with blood cancers, using bone marrow from a relative. The bone marrow for this transplant comes from a relative who is a half-match or "haplo" match to you. Possible donors include parents, siblings, and children.

"Mini" transplants have been given to many people with various cancers but are considered experimental. Over 200 people at Johns Hopkins have received mini transplants with high doses of cyclophosphamide after the transplant. However, the chemotherapy combination and other treatment given before those transplants were different from what is in this study. Although all of the chemotherapy and immune-lowering drugs used in this study are approved by the Food and Drug Administration (FDA), the combination of medications used in this study are not FDA approved and are experimental.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Reduced-intensity, Related-donor Allogeneic BMT With Fludarabine, Busulfan, and High-dose Posttransplantation Cyclophosphamide for Hematologic Malignancies
Study Start Date : August 2010
Actual Primary Completion Date : May 2012
Actual Study Completion Date : May 2012


Arm Intervention/treatment
Experimental: Transplant
Reduced-intensity transplant with a fludarabine- and busulfan-based preparative regimen. GVHD prophylaxis with cyclophosphamide, tacrolimus, and mycophenolate mofetil.
Drug: Fludarabine
30 mg/m^2 IV daily on Day -6 through Day -2.
Other Names:
  • Fludara
  • Flu

Drug: Busulfan
1 mg/kg PO OR 0.8 mg/kg IV four times daily on Day -6 through Day -3.
Other Names:
  • Busulfex
  • Myleran

Drug: Cyclophosphamide
50 mg/kg IV daily on Day +3 and Day +4.
Other Names:
  • CTX
  • Cytoxan
  • Cy

Drug: Mycophenolate Mofetil
15 mg/kg PO three times daily (max daily dose of 3g) starting on Day +5.
Other Names:
  • MMF
  • CellCept

Drug: Tacrolimus
Dosed based on drug levels; begin on Day +5 at 1 mg IV daily.
Other Names:
  • FK506
  • FK-506
  • Prograf




Primary Outcome Measures :
  1. Chimerism in Unsorted Peripheral Blood [ Time Frame: Day 60 ]
    Percentage of participants achieving full-donor chimerism in unsorted peripheral blood.

  2. Chimerism in CD3+ Sorted Peripheral Blood [ Time Frame: Day 60 ]
    Percentage of participants achieving full-donor chimerism in CD3+ sorted peripheral blood


Secondary Outcome Measures :
  1. Overall Survival [ Time Frame: 1 year ]
    Percentage of participants alive

  2. Progression-free Survival [ Time Frame: 1 year ]
    Percentage of participants alive without disease relapse or progression.

  3. Incidence of Relapse [ Time Frame: 1 year ]
    Percentage of participants experiencing disease relapse or progression

  4. Non-relapse Mortality [ Time Frame: 1 year ]
    Percentage of participants who died due to BMT-related reasons

  5. Incidence of Graft-versus-host-disease (GVHD) [ Time Frame: 1 year ]
    Percentage of participants experiencing acute and chronic GVHD. Acute GVHD is graded by Przepiorka criteria. Chronic GVHD is graded by NIH consensus criteria and Seattle criteria.

  6. Graft Failure [ Time Frame: Day 60 ]
    Percentage of participants who failed to engraft.



Information from the National Library of Medicine

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Ages Eligible for Study:   6 Months to 75 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • First-degree related donor who is at minimum HLA haploidentical
  • Eligible diagnoses:

    1. Low-grade non-Hodgkin's lymphoma or plasma cell neoplasm that has progressed during multiagent therapy, failed at least two prior therapies (excluding single agent rituximab and single agent steroids), or in the case of lymphoma undergone histological conversion:

      • Follicular grade 1 or 2 lymphoma
      • Follicular lymphoma not otherwise specified
      • Marginal zone (or MALT) lymphoma
      • Lymphoplasmacytic lymphoma / Waldenstrom's macroglobulinemia
      • Hairy cell leukemia
      • Small lymphocytic lymphoma (SLL) or chronic lymphocytic leukemia (CLL)
      • Prolymphocytic leukemia
      • Low grade B-cell lymphoma, unspecified
      • Multiple myeloma
      • Plasma cell leukemia
    2. Poor-risk SLL or CLL, defined by an 11q or 17p deletion, histological conversion, or disease progression < 6 months after a purine analog-containing regimen
    3. Aggressive lymphoma that has failed at least one prior regimen of multiagent chemotherapy, and patient is either ineligible for autologous BMT or autologous BMT is not recommended:

      • Hodgkin lymphoma
      • Follicular grade 3 lymphoma
      • Mantle cell lymphoma or leukemia
      • Diffuse large B-cell lymphoma (excluding primary CNS lymphoma). Eligible subtypes include primary mediastinal large B-cell lymphoma, T-cell rich large B-cell lymphoma, and large B-cell lymphoma not otherwise specified.
      • Burkitt's lymphoma/leukemia
      • Atypical Burkitt's lymphoma/leukemia (high grade B-cell lymphoma, unclassified, including that with features intermediate between Burkitt's and diffuse large B-cell lymphoma)
      • Anaplastic large cell lymphoma
      • Plasmablastic lymphoma
      • Peripheral T-cell lymphoma
    4. Relapsed or refractory acute leukemia in second or subsequent remission
    5. Poor-risk acute leukemia in first remission
    6. AML with at least one of the following:

      • AML arising from MDS or a myeloproliferative disorder, or secondary AML
      • Presence of Flt3 internal tandem duplications
      • Poor-risk cytogenetics
      • Primary refractory disease

        • ALL (leukemia and/or lymphoma) with at least one of the following:
      • Adverse cytogenetics
      • Clear evidence of hypodiploidy
      • Primary refractory disease

        • Biphenotypic leukemia
        • MDS with at least one of the following features:
        • Poor-risk cytogenetics
        • IPSS score of INT-2 or greater
        • Treatment-related MDS
        • MDS diagnosed before age 21 years
        • Progression on or lack of response to standard DNA-methyltransferase inhibitor therapy
        • Life-threatening cytopenias, including those generally requiring greater than weekly transfusions
    7. Interferon- or imatinib-refractory CML in first chronic phase, or non-blast crisis CML beyond first chronic phase
    8. Philadelphia chromosome negative myeloproliferative disease (including myelofibrosis)
    9. Chronic myelomonocytic leukemia
    10. Juvenile myelomonocytic leukemia

      • For patients with SLL, CLL, or prolymphocytic leukemia, < 20% of bone marrow cellularity involved by this process
      • Adequate end-organ function:
  • Left ventricular ejection fraction greater than or equal to 35%
  • Bilirubin ≤ 3.0 mg/dL (unless due to Gilbert's syndrome or hemolysis), and ALT and AST < 5 x ULN
  • FEV1 and FVC > 40% of predicted; or in pediatric patients, if unable to perform pulmonary function tests due to young age, oxygen saturation >92% on room air

    • ECOG performance status < 2 or Karnofsky or Lansky score > 60

Exclusion Criteria:

  • Pregnant or breast-feeding
  • Uncontrolled infection Note: Infection is permitted if there is evidence of response to medication. Eligibility of HIV infected patients will be determined on a case-by-case basis.
  • Any previous BMT within 3 months prior to start of conditioning
  • Active extra-medullary leukemia or known active Central Nervous System (CNS) involvement by malignancy. Such disease treated into remission is permitted.

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): NCT01135329


Locations
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United States, Maryland
The Sydney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States, 21231
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Investigators
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Principal Investigator: Yvette Kasamon, M.D. Johns Hopkins University

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Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT01135329     History of Changes
Other Study ID Numbers: J1046
NA_00039363 ( Other Identifier: JHM IRB )
First Posted: June 2, 2010    Key Record Dates
Results First Posted: July 3, 2018
Last Update Posted: July 3, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
High-risk acute leukemia in first remission
Lymphoma
Hodgkin's lymphoma
Non hodgkin's lymphoma
Leukemia
Acute myeloid leukemia (AML)
Acute lymphoblastic leukemia(ALL)
Chronic myeloid leukemia (CML)
Chronic Myelomonocytic (CMML)
Myelodysplastic syndrome (MDS)
Relapsed leukemia in remission
Cyclophosphamide
High-dose cyclophosphamide
Fludarabine
Busulfan
Allogeneic
Nonmyeloablative
Reduced intensity
Haploidentical
Bone marrow transplant (BMT)
Additional relevant MeSH terms:
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Antibiotics, Antineoplastic
Antibiotics, Antitubercular
Anti-Bacterial Agents
Lymphoma
Leukemia
Preleukemia
Myelodysplastic Syndromes
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Vidarabine
Mycophenolic Acid
Cyclophosphamide
Busulfan
Fludarabine
Fludarabine phosphate
Tacrolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action