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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01135329
Recruitment Status : Terminated (The stopping rule was met and hence the study was closed)
First Posted : June 2, 2010
Last Update Posted : April 17, 2014
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, Busulfan, Cyclophosphamide, 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.

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

Intervention Details:
  • Drug: Fludarabine, Busulfan, Cyclophosphamide, Tacrolimus,
    Fludarabine 30 mg/m2 IV once a day for 4 days Busulfan 0.8 mg/kg IV every 12 hours for 4 days Cyclophosphamide 50 mg/kg IV daily for 2 days
    Other Names:
    • BMT
    • Allogeneic
    • Transplantation

Primary Outcome Measures :
  1. Estimate the proportion of patients achieving full donor chimerism [ Time Frame: Day 60 ]
    After reduced-intensity, partially (Human leukocyte antigen) HLA-mismatched or HLA-matched BMT with fludarabine, busulfan, and post-grafting immunosuppression that includes high-dose cyclophosphamide, estimate the proportion achieving full donor chimerism by Day 60 in unsorted and CD3+ sorted peripheral blood.

Secondary Outcome Measures :
  1. Graft-versus-host disease (GVHD) [ Time Frame: Day 60 ]
    Estimate the cumulative incidence of acute and chronic Graft-versus-host disease (GVHD), and describe other major toxicities.

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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

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 identifier (NCT number): NCT01135329

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
Principal Investigator: Yvette Kasamon, M.D. Johns Hopkins University

Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Identifier: NCT01135329     History of Changes
Other Study ID Numbers: J1046
NA_00039363 ( Other Identifier: JHM IRB )
First Posted: June 2, 2010    Key Record Dates
Last Update Posted: April 17, 2014
Last Verified: April 2014

Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
Hodgkin's lymphoma
Non hodgkin's lymphoma
Acute myeloid leukemia (AML)
Acute lymphoblastic leukemia(ALL)
Chronic myeloid leukemia (CML)
Chronic Myelomonocytic (CMML)
Myelodysplastic syndrome (MDS)
High-risk acute leukemia in first remission
Relapsed leukemia in remission
High-dose cyclophosphamide
Reduced intensity
Bone marrow transplant (BMT)

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Fludarabine phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Calcineurin Inhibitors
Enzyme Inhibitors