Clinical Trials /

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

NCT01342289

Description:

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.

Related Conditions:
  • Acute Biphenotypic Leukemia
  • Acute Leukemia
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Burkitt Lymphoma
  • Chronic Lymphocytic Leukemia
  • Chronic Myeloid Leukemia
  • Chronic Myelomonocytic Leukemia
  • Hodgkin Lymphoma
  • Juvenile Myelomonocytic Leukemia
  • Mantle Cell Lymphoma
  • Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma
  • Myelodysplastic Syndromes
  • Myeloproliferative Neoplasm
  • Non-Hodgkin Lymphoma
  • Peripheral T-Cell Lymphoma
  • Plasma Cell Leukemia
  • Plasma Cell Neoplasm
  • Small Lymphocytic Lymphoma
  • T-Cell Prolymphocytic Leukemia
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Shorter Course Tacrolimus After Nonmyeloablative, Related Donor BMT With High-dose Posttransplantation Cyclophosphamide
  • Official Title: Shortened-duration Tacrolimus Following Nonmyeloablative, Related Donor BMT With High-dose Posttransplantation Cyclophosphamide

Clinical Trial IDs

  • ORG STUDY ID: J1151
  • SECONDARY ID: NA_00048378
  • NCT ID: NCT01342289

Conditions

  • Hodgkin's Lymphoma
  • Leukemia
  • Myelodysplastic Syndrome(MDS)
  • Multiple Myeloma
  • Non Hodgkin's Lymphoma

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions

Eligibility Criteria

        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.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:6 Months
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Incidence of GVHD
Time Frame:Day 180, and beyond Day 180 (up to 7 years)
Safety Issue:
Description: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.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Trial Keywords

  • Nonmyeloablative
  • Allogeneic
  • Bone Marrow Transplant (BMT)
  • Tacrolimus
  • Cyclophosphamide

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