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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Sidney Kimmel Comprehensive Cancer Center
Sponsor:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01342289
First received: April 21, 2011
Last updated: September 29, 2014
Last verified: September 2014
  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.


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

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Shortened-duration Tacrolimus Following Nonmyeloablative, Related Donor BMT With High-dose Posttransplantation Cyclophosphamide

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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.

  • To estimate the tolerability of reduced-duration tacrolimus on patients following nonmyeloablative transplant. [ Time Frame: Day 60 - Day 180 ] [ Designated as safety issue: No ]
    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:
  • Incidence of GVHD [ Time Frame: Day 180, and beyond Day 180 (up to 7 years) ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 140
Study Start Date: July 2011
Estimated Study Completion Date: June 2022
Estimated Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)
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
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.

  Eligibility

Ages Eligible for Study:   6 Months to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  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: NCT01342289

Contacts
Contact: Yvette Kasamon, M.D. 410-955-8839 ykasamo1@jhmi.edu

Locations
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center Recruiting
Baltimore, Maryland, United States, 21231
Contact: Yvette Kasamon, M.D.    410-955-8839    ykasamo1@jhmi.edu   
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: NCT01342289     History of Changes
Other Study ID Numbers: J1151, NA_00048378
Study First Received: April 21, 2011
Last Updated: September 29, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
Nonmyeloablative
Allogeneic
Bone Marrow Transplant (BMT)
Tacrolimus
Cyclophosphamide

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

ClinicalTrials.gov processed this record on October 23, 2014