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Hodgkin's LymphomaPhase 1NCT01342289

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

A Phase 1 study testing Cyclophosphamide, Fludarabine and Total body irradiation in people with Hodgkin's Lymphoma and Leukemia, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 6 months to 75 years
What is being tested?
Cyclophosphamide, Fludarabine and Total body irradiation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
127 participants
Where
1 siteUnited States
Study dates
Aug 2011to Mar 2018
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 6 months to 75 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 0.5-75 years
  • Suitable first-degree related, HLA haploidentical or HLA-matched donor
  • Eligible diagnoses:
  • 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
  • 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.
  • 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.
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  • 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
  • For patients with SLL, CLL, or PLL, < 20% of bone marrow cellularity involved by this process (to lower risk of graft rejection).
  • Relapsed, refractory, or progressive acute leukemia in second or subsequent remission, with remission defined as <5% bone marrow blasts morphologically.
  • 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
  • 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
  • Interferon- or imatinib-refractory CML in first chronic phase, or CML in second or subsequent chronic phase
  • Philadelphia chromosome negative myeloproliferative disease (including myelofibrosis)
  • Chronic myelomonocytic leukemia
  • Juvenile myelomonocytic leukemia
  • One of the following:
  • 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
  • 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.

Who cannot join

  • Active extramedullary leukemia or known active Central Nervous System (CNS) involvement by malignancy.
  • Previous Bone marrow transplant (BMT) less than 3 months prior to start of conditioning.
  • Inadequate end-organ function as measured by:
  • Left ventricular ejection fraction less than or equal to 35% or shortening fraction less than 25%
  • 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
  • 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
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  • Previous allogeneic BMT (syngeneic BMT permissible).
  • Pregnant or breast-feeding.
  • Uncontrolled infection.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Sidney Kimmel Comprehensive Cancer Center

    Baltimore, Maryland, 21231

Other trials in United States

About this study

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

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.

Read the 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.

Keywords
Nonmyeloablative, Allogeneic, Bone Marrow Transplant (BMT), Tacrolimus, Cyclophosphamide
Medical subject headings
Hodgkin Disease, Leukemia, Myelodysplastic Syndromes, Multiple Myeloma, Lymphoma, Non-Hodgkin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CyclophosphamideDrug

    Also called Cytoxan

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

  • FludarabineDrug

    Also called Fludara

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

  • Total body irradiationRadiation

    Also called TBI

    Day -1: 200 centigray in one fraction.

  • Mycophenolate MofetilDrug

    Also called MMF, CellCept

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

  • Tacrolimus 60Drug

    Also called FK-506, Prograf

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

  • Tacrolimus 90Drug

    Also called FK-506, Prograf

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

  • Tacrolimus 120Drug

    Also called FK-506, Prograf

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

  • Bone marrow transplantBiological

    Also called BMT

    Donor stem cells infused IV on Day 0.

Study groups in NCT01342289
Study groupRoleWhat they receive
Tacrolimus 60ExperimentalNon-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.
Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Radiation: Total body irradiation; Drug: Mycophenolate Mofetil; Drug: Tacrolimus 60; Biological: Bone marrow transplant
Tacrolimus 90ExperimentalNon-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.
Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Radiation: Total body irradiation; Drug: Mycophenolate Mofetil; Drug: Tacrolimus 90; Biological: Bone marrow transplant
Tacrolimus 120ExperimentalNon-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.
Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Radiation: Total body irradiation; Drug: Mycophenolate Mofetil; Drug: Tacrolimus 120; Biological: Bone marrow transplant

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety of reduced-dose tacrolimus as assessed by Percentage of Participants with severe graft versus host disease (GVHD)

    Percentage of participants with severe graft versus host disease (GVHD) defined as grade III-IV acute GVHD or extensive chronic GVHD. Acute GVHD is defined by the Przepiorka criteria, which stages the degree of organ involvement in the skin, liver, and gastrointestinal (GI) tract, based on severity, with Stage 1+ being least severe and stage 4+ being the most severe. Grading of acute GVHD is as follows: Grade I (skin involvement stages 1+ to 2+, with no liver or GI involvement), Grade II (skin involvement stages 1+ to 3+, liver 1+, GI tract 1+), Grade III (skin involvement stages 2+ to 3+, liver 1+, GI tract 2+ to 4+), Grade IV (skin involvement stages 4+, Liver 4+). Chronic GVHD is defined by the NIH consensus criteria. This system gives scores from 0 to 3 for Karnofsky performance score, skin, mouth, eyes, gastrointestinal, liver, lungs, joints, and genitals, as well as an overall severity. Higher scores indicate more severe disease. Scores are not totaled or added up.

    Measured: Day 5 - Day 120

  2. Tolerability of tacrolimus as assessed by percentage of participants with treatment-emergent adverse events

    Percentage of participants with grade 3-4 toxicity by CTCAE 4.0 attributable to tacrolimus.

    Measured: Up to 120 days

Secondary outcomes (8)

  1. Percentage of participants experiencing acute GVHD

    Percentage of participants with grade II-IV and III-IV acute GVHD. Acute GVHD is defined by the Przepiorka criteria, which stages the degree of organ involvement in the skin, liver, and gastrointestinal (GI) tract, based on severity, with Stage 1+ being least severe and stage 4+ being the most severe. Grading of acute GVHD is as follows: Grade I (skin involvement stages 1+ to 2+, with no liver or GI involvement), Grade II (skin involvement stages 1+ to 3+, liver 1+, GI tract 1+), Grade III (skin involvement stages 2+ to 3+, liver 1+, GI tract 2+ to 4+), Grade IV (skin involvement stages 4+, Liver 4+).

    Measured: Up to 7 years

  2. Percentage of participants experiencing chronic GVHD

    Percentage of participants with chronic GVHD. Chronic GVHD is defined by the NIH consensus criteria. This system gives scores from 0 to 3 for Karnofsky performance score, skin, mouth, eyes, gastrointestinal, liver, lungs, joints, and genitals, as well as an overall severity (mild, moderate, or severe). Higher scores indicate more severe disease. Scores are not totalled or added up.

    Measured: Up to 7 years

  3. Disease relapse

    Percentage of participants experiencing disease relapse or progression.

    Measured: Up to 7 years

  4. Non-relapse mortality

    Percentage of participants who died for any reason other than disease relapse or progression.

    Measured: Up to 7 years

  5. Use of immunosuppression

    Percentage of participants who: required use of steroids; required use of non-steroid immunosuppression; and who were able to discontinue immunosuppression after starting treatment.

    Measured: Up to 2 years

  6. Survival

    Percentage of participants who are alive with and without disease relapse or progression.

    Measured: Up to 7 years

  7. Chimerism

    Percentage of participants who had >=95% donor chimerism.

    Measured: 30 and 60 days

  8. Engraftment

    Percentage of participants who had successful engraftment of neutrophils and platelets.

    Measured: 30 and 60 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Apr 2011 (estimated)
  2. Study startAug 2011
  3. Primary completionMar 2018
  4. Study completionMar 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
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.
Masking
None (open label)
Enrolment
127 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01342289
Sponsor's protocol ID
J1151
Other IDs
NA_00048378
Status last verified
Oct 2018
First submitted
21 Apr 2011
Last updated
17 Oct 2018
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • 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.

    PubMed 29353109

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cyclophosphamide, Fludarabine and Total body irradiation in people with Hodgkin's Lymphoma and Leukemia, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety of reduced-dose tacrolimus as assessed by Percentage of Participants with severe graft versus host disease (GVHD) (time frame: Day 5 - Day 120). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01342289, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Oct 2018.

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