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

This study has been terminated.
(The stopping rule was met and hence the study was closed)
Sponsor:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01135329
First received: June 1, 2010
Last updated: April 16, 2014
Last verified: April 2014
  Purpose

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 Intervention Phase
Lymphoma
Leukemia
Myelodysplastic Syndrome
Drug: Fludarabine, Busulfan, Cyclophosphamide, Tacrolimus,
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Reduced-intensity, Related-donor Allogeneic BMT With Fludarabine, Busulfan, and High-dose Posttransplantation Cyclophosphamide for Hematologic Malignancies

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Estimate the proportion of patients achieving full donor chimerism [ Time Frame: Day 60 ] [ Designated as safety issue: No ]
    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:
  • Graft-versus-host disease (GVHD) [ Time Frame: Day 60 ] [ Designated as safety issue: Yes ]
    Estimate the cumulative incidence of acute and chronic Graft-versus-host disease (GVHD), and describe other major toxicities.


Enrollment: 15
Study Start Date: August 2010
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
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
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.

  Eligibility

Ages Eligible for Study:   6 Months to 75 Years
Genders Eligible for Study:   Both
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.
  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: NCT01135329

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

No publications provided

Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01135329     History of Changes
Other Study ID Numbers: J1046, NA_00039363
Study First Received: June 1, 2010
Last Updated: April 16, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
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)
High-risk acute leukemia in first remission
Relapsed leukemia in remission
Cyclophosphamide
High-dose cyclophosphamide
Fludarabine
Busulfan
Allogeneic
Nonmyeloablative
Reduced intensity
Haploidentical
Bone marrow transplant (BMT)

Additional relevant MeSH terms:
Leukemia
Lymphoma
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Pathologic Processes
Precancerous Conditions
Busulfan
Cyclophosphamide
Fludarabine
Fludarabine phosphate
Alkylating Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists

ClinicalTrials.gov processed this record on October 30, 2014