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Shortened-duration Tacrolimus Following Nonmyeloablative, Related Donor BMT With High-dose Posttransplantation Cyclophosphamide

Phase 1/Phase 2
6 Months
75 Years
Open (Enrolling)
Hodgkin's Lymphoma, Leukemia, Myelodysplastic Syndrome(MDS), Multiple Myeloma, Non Hodgkin's Lymphoma

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Trial Information

Shortened-duration Tacrolimus Following Nonmyeloablative, Related Donor BMT With High-dose Posttransplantation Cyclophosphamide

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.

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

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

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

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

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.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome 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

Outcome 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.

Outcome Time Frame:

Day 5 - Day 120

Safety Issue:


Principal Investigator

Yvette Kasamon, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Johns Hopkins University


United States: Institutional Review Board

Study ID:




Start Date:

July 2011

Completion Date:

June 2022

Related Keywords:

  • Hodgkin's Lymphoma
  • Leukemia
  • Myelodysplastic Syndrome(MDS)
  • Multiple Myeloma
  • Non Hodgkin's Lymphoma
  • Nonmyeloablative
  • Allogeneic
  • Bone Marrow Transplant (BMT)
  • Tacrolimus
  • Cyclophosphamide
  • Hodgkin Disease
  • Leukemia
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Myelodysplastic Syndromes
  • Preleukemia



Sidney Kimmel Comprehensive Cancer CenterLutherville, Maryland