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

NCT ID: NCT01342289

Last Updated: 2018-10-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

127 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-08-31

Study Completion Date

2018-03-31

Brief Summary

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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

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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.

Conditions

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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Participants were initially enrolled on the 90-day arm. When that arm completed enrollment, participants were enrolled on the 120-day arm while safety of the 90-day arm was evaluated. The 90-day arm was found to be safe, so participants were then enrolled on the 60-day arm for the remainder of the study.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Tacrolimus 60

Non-myeloablative bone marrow transplant with fludarabine, cyclophosphamide, total body irradiation conditioning regimen and cyclophosphamide, mycophenolate mofetil, and tacrolimus prophylaxis for graft-versus-host disease (GVHD). Tacrolimus was given for 60 days.

Group Type EXPERIMENTAL

Cyclophosphamide

Intervention Type DRUG

Days -6 and -5: 14.5 mg/kg/day IV. Days 3 and 4: 50 mg/kg/day IV.

Fludarabine

Intervention Type DRUG

Days -6, -5, -4, -3, and -2: 30 mg/m\^2/day IV.

Total body irradiation

Intervention Type RADIATION

Day -1: 200 centigray in one fraction.

Mycophenolate Mofetil

Intervention Type DRUG

Days 5 to 35: 15 mg/kg PO three times per day; max daily dose 1 g.

Tacrolimus 60

Intervention Type DRUG

Begin dosing at 1 mg IV daily on Day 5. Dose is titrated according to serum levels. Stop at Day 60.

Bone marrow transplant

Intervention Type BIOLOGICAL

Donor stem cells infused IV on Day 0.

Tacrolimus 90

Non-myeloablative bone marrow transplant with fludarabine, cyclophosphamide, total body irradiation conditioning regimen and cyclophosphamide, mycophenolate mofetil, and tacrolimus prophylaxis for graft-versus-host disease (GVHD). Tacrolimus was given for 90 days.

Group Type EXPERIMENTAL

Cyclophosphamide

Intervention Type DRUG

Days -6 and -5: 14.5 mg/kg/day IV. Days 3 and 4: 50 mg/kg/day IV.

Fludarabine

Intervention Type DRUG

Days -6, -5, -4, -3, and -2: 30 mg/m\^2/day IV.

Total body irradiation

Intervention Type RADIATION

Day -1: 200 centigray in one fraction.

Mycophenolate Mofetil

Intervention Type DRUG

Days 5 to 35: 15 mg/kg PO three times per day; max daily dose 1 g.

Tacrolimus 90

Intervention Type DRUG

Begin dosing at 1 mg IV daily on Day 5. Dose is titrated according to serum levels. Stop at Day 90.

Bone marrow transplant

Intervention Type BIOLOGICAL

Donor stem cells infused IV on Day 0.

Tacrolimus 120

Non-myeloablative bone marrow transplant with fludarabine, cyclophosphamide, total body irradiation conditioning regimen and cyclophosphamide, mycophenolate mofetil, and tacrolimus prophylaxis for graft-versus-host disease (GVHD). Tacrolimus was given for 120 days.

Group Type EXPERIMENTAL

Cyclophosphamide

Intervention Type DRUG

Days -6 and -5: 14.5 mg/kg/day IV. Days 3 and 4: 50 mg/kg/day IV.

Fludarabine

Intervention Type DRUG

Days -6, -5, -4, -3, and -2: 30 mg/m\^2/day IV.

Total body irradiation

Intervention Type RADIATION

Day -1: 200 centigray in one fraction.

Mycophenolate Mofetil

Intervention Type DRUG

Days 5 to 35: 15 mg/kg PO three times per day; max daily dose 1 g.

Tacrolimus 120

Intervention Type DRUG

Begin dosing at 1 mg IV daily on Day 5. Dose is titrated according to serum levels. Stop at Day 120.

Bone marrow transplant

Intervention Type BIOLOGICAL

Donor stem cells infused IV on Day 0.

Interventions

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Cyclophosphamide

Days -6 and -5: 14.5 mg/kg/day IV. Days 3 and 4: 50 mg/kg/day IV.

Intervention Type DRUG

Fludarabine

Days -6, -5, -4, -3, and -2: 30 mg/m\^2/day IV.

Intervention Type DRUG

Total body irradiation

Day -1: 200 centigray in one fraction.

Intervention Type RADIATION

Mycophenolate Mofetil

Days 5 to 35: 15 mg/kg PO three times per day; max daily dose 1 g.

Intervention Type DRUG

Tacrolimus 60

Begin dosing at 1 mg IV daily on Day 5. Dose is titrated according to serum levels. Stop at Day 60.

Intervention Type DRUG

Tacrolimus 90

Begin dosing at 1 mg IV daily on Day 5. Dose is titrated according to serum levels. Stop at Day 90.

Intervention Type DRUG

Tacrolimus 120

Begin dosing at 1 mg IV daily on Day 5. Dose is titrated according to serum levels. Stop at Day 120.

Intervention Type DRUG

Bone marrow transplant

Donor stem cells infused IV on Day 0.

Intervention Type BIOLOGICAL

Other Intervention Names

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Cytoxan Fludara TBI MMF CellCept FK-506 Prograf FK-506 Prograf FK-506 Prograf BMT

Eligibility Criteria

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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.
Minimum Eligible Age

6 Months

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Richard Jones, M.D.

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

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Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States

Site Status

Countries

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United States

References

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Kasamon YL, Fuchs EJ, Zahurak M, Rosner GL, Symons HJ, Gladstone DE, Huff CA, Swinnen LJ, Brodsky RA, Matsui WH, Borrello I, Shanbhag S, Cooke KR, Ambinder RF, Luznik L, Bolanos-Meade J, Jones RJ. Shortened-Duration Tacrolimus after Nonmyeloablative, HLA-Haploidentical Bone Marrow Transplantation. Biol Blood Marrow Transplant. 2018 May;24(5):1022-1028. doi: 10.1016/j.bbmt.2018.01.011. Epub 2018 Jan 17.

Reference Type DERIVED
PMID: 29353109 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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NA_00048378

Identifier Type: OTHER

Identifier Source: secondary_id

J1151

Identifier Type: -

Identifier Source: org_study_id

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