Shorter Course Tacrolimus After Nonmyeloablative, Related Donor BMT With High-dose Posttransplantation Cyclophosphamide

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: NCT01342289
Recruitment Status : Active, not recruiting
First Posted : April 27, 2011
Last Update Posted : July 13, 2017
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center

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

Condition or disease Intervention/treatment Phase
Hodgkin's Lymphoma Leukemia Myelodysplastic Syndrome(MDS) Multiple Myeloma Non Hodgkin's Lymphoma Procedure: Bone Marrow Transplant Phase 1 Phase 2

Detailed Description:

The main goal is to learn whether a drug called tacrolimus, which is an immune-lowering drug (an immunosuppressant) given after transplant to help prevent certain complications, can be given safely for a shorter period of time than it has been in the past.

At the present time there are few or no cures for your type of disease outside of a bone marrow transplant. 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. In order to help the bone marrow grow, or "take", inside your body, you will receive chemotherapy and radiation before the transplant. After the transplant you will receive high doses of cyclophosphamide (Cytoxan®) along with other medications to lower the immune system, tacrolimus. These medications may lower the risk of graft versus host disease (GVHD) and of your body rejecting the bone marrow graft.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 127 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Shortened-duration Tacrolimus Following Nonmyeloablative, Related Donor BMT With High-dose Posttransplantation Cyclophosphamide
Study Start Date : July 2011
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : June 2022

Intervention Details:
    Procedure: Bone Marrow Transplant
    Preparative regimen consists of Fludarabine - 30 mg/m2/day , Cytoxan - 14.5 mg/kg/day , and Total Body Irradiation administered in a single fraction , with posttransplantation high-dose Cytoxan - 50 mg/kg IV, Mycophenolate mofetil - 15 mg/kg PO TID, and tacrolimus- starting dose is 1 mg IV QD.
    Other Names:
    • Fludara
    • Cyclophosphamide
    • TBI
    • High-dose Cy
    • MMF
    • Tacrolimus
    • BMT

Primary Outcome Measures :
  1. Evaluate the safety of reduced-duration tacrolimus (from Day 5 through either To estimate the number of patients with GVHD as a measure of the safety of reduced-duration tacrolimus [ Time Frame: Day 5 - Day 120 ]
    Immunosuppression must be sufficient to prevent excessive rates of GVHD including severe GVHD. There are presently no published data on the minimum required duration of tacrolimus after nonmyeloablative, partially HLA-mismatched BMT that includes high-dose Cy as part of postgrafting immunosuppression.

  2. To estimate the tolerability of reduced-duration tacrolimus on patients following nonmyeloablative transplant. [ Time Frame: Day 60 - Day 180 ]
    Tacrolimus levels will be monitored. Patients who develop a prohibitive toxicity to tacrolimus (resulting in earlier than scheduled discontinuation of tacrolimus) will be considered unevaluable for the primary endpoint. The duration of tacrolimus will be evaluated at Day 90. If tacrolimus at Day 90 appears feasible, then it will be continued until Day 120 with analogous monitoring rules.

Secondary Outcome Measures :
  1. Incidence of GVHD [ Time Frame: Day 180, and beyond Day 180 (up to 7 years) ]
    Estimate the incidences of acute grade II-IV GVHD, acute grade III or higher GVHD, chronic GVHD, graft failure, relapse, and nonrelapse mortality between the date of early tacrolimus cessation and Day 180, and beyond Day 180.

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

Inclusion Criteria:

  1. 0.5-75 years
  2. Suitable first-degree related, HLA haploidentical or HLA-matched donor
  3. Eligible diagnoses:

    a. Low-grade non-Hodgkin's lymphoma or plasma cell neoplasm with either of the following, and with stable disease or better prior to transplantation: i. Progressed during multiagent therapy, failed at least two prior therapies (excluding single agent rituximab), or there is evidence of prior transformation ii. SLL or CLL with 11q or 17p deletion or with progression < 6 months after a purine analog-containing regimen

    b. Relapsed, refractory, or progressive aggressive non Hodgkin's lymphoma (including mantle cell lymphoma), with PR or better prior to transplantation, and autologous BMT is not recommended. Note: Patients with Burkitt's, atypical Burkitt's, or acute lymphoblastic lymphoma must be in CR.

    c. Relapsed, refractory, or progressive Hodgkin's lymphoma meeting one of the following criteria, and autologous BMT is not recommend: i. PR or better prior to transplantation. ii. Stable disease prior to transplantation, provided that the disease is low-volume and disease control is regarded as sufficient to proceed with BMT. Eligibility of such patients will be determined on a case-by-case basis with the PI or co-PI.

    d. One of the following poor-risk lymphomas or plasma cell neoplasms, in PR or better prior to transplantation: i. Transformed lymphoma ii. T-cell PLL iii. Peripheral T-cell lymphoma iv. NK or NK/T-cell lymphoma v. Blastic/blastoid mantle cell lymphoma vi. Plasma cell leukemia

    e. For patients with SLL, CLL, or PLL, < 20% of bone marrow cellularity involved by this process (to lower risk of graft rejection).

    f. Relapsed, refractory, or progressive acute leukemia in second or subsequent remission, with remission defined as <5% bone marrow blasts morphologically.

    g. Poor-risk acute leukemia in first remission, with remission defined as <5% bone marrow blasts morphologically: i. 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 ii. ALL (leukemia and/or lymphoma) with at least one of the following: Poor-risk cytogenetics Clear evidence of hypodiploidy Primary refractory disease iii. Biphenotypic leukemia

    h. MDS with at least one of the following poor-risk features: i. Poor-risk cytogenetics ii. IPSS score of INT-2 or greater iii. Treatment-related or secondary MDS iv. MDS diagnosed before age 21 years v. Progression on or lack of response to standard DNA-methyltransferase inhibitor therapy vi. Life-threatening cytopenias, including those requiring frequent transfusions

    i. Interferon- or imatinib-refractory CML in first chronic phase, or CML in second or subsequent chronic phase

    j. Philadelphia chromosome negative myeloproliferative disease (including myelofibrosis)

    k. Chronic myelomonocytic leukemia

    l. Juvenile myelomonocytic leukemia

  4. One of the following:

    1. Cytotoxic chemotherapy, alemtuzumab, or an adequate course of 5-azacitidine or decitabine must have been given within 3 months prior to start of conditioning or
    2. Previous BMT within 6 months prior to start of conditioning. --Note: Patients who have received treatment outside of these windows may be eligible if it is deemed sufficient to reduce graft rejection risk; this will be decided on a case-by-case basis by the PI or co-PI.

Exclusion Criteria:

  1. Active extramedullary leukemia or known active Central Nervous System (CNS) involvement by malignancy.
  2. Previous Bone marrow transplant (BMT) less than 3 months prior to start of conditioning.
  3. Inadequate end-organ function as measured by:

    1. Left ventricular ejection fraction less than or equal to 35% or shortening fraction less than 25%
    2. Bilirubin greater than or equal to 3.0 mg/dL (unless due to Gilbert's syndrome or hemolysis), and ALT and AST greater than or equal to 5 x ULN
    3. FEV1 and FVC less than or equal to 40% of predicted; or if unable to perform pulmonary function tests due to young age, oxygen saturation less than 92% on room air
  4. Previous allogeneic BMT (syngeneic BMT permissible).
  5. Pregnant or breast-feeding.
  6. Uncontrolled infection.

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): NCT01342289

United States, Maryland
Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States, 21231
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Principal Investigator: Richard Jones, M.D. Johns Hopkins University

Responsible Party: Sidney Kimmel Comprehensive Cancer Center Identifier: NCT01342289     History of Changes
Other Study ID Numbers: J1151
NA_00048378 ( Other Identifier: JHMIRB )
First Posted: April 27, 2011    Key Record Dates
Last Update Posted: July 13, 2017
Last Verified: July 2017

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
Bone Marrow Transplant (BMT)

Additional relevant MeSH terms:
Multiple Myeloma
Myelodysplastic Syndromes
Lymphoma, Non-Hodgkin
Hodgkin Disease
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Bone Marrow Diseases
Precancerous Conditions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents