AzTrials
AzTrials

LymphomaPhase 2NCT00946023

Optimized Donor Selection, Nonmyeloablative BMT for B-cell Lymphomas With Post-transplantation Cy and Rituximab

A Phase 2 study testing Fludarabine, Cyclophosphamide and Total body irradiation in people with Lymphoma and B-cell Lymphoma, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

This phase II trial is studying how well giving fludarabine and cyclophosphamide together with total-body irradiation and rituximab works in treating patients with B-cell lymphoma or chronic lymphocytic leukemia who are undergoing an allogeneic (donor) bone marrow transplant. Read more about this study

Who is it for?
Ages 1 year to 75 years
Conditions the study is for
Lymphoma, B-cell Lymphoma, Non Hodgkin Lymphoma
What is being tested?
Fludarabine, Cyclophosphamide and Total body irradiation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
135 participants
Where
1 siteUnited States
Study dates
Jul 2009to 17 Jul 2013
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 1 year to 75 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Poor-risk CD20+, B-cell lymphoma, as follows:
  • Low grade B-cell lymphoma that has failed at least two prior therapies (excluding single agent rituximab), or undergone histologic conversion (if histologic conversion, PR or CR is required):
  • Follicular grade 1 or 2 lymphoma
  • Follicular lymphoma not otherwise specified
  • Marginal zone (or MALT) lymphoma
  • Lymphoplasmacytic lymphoma / Waldenstrom's macroglobulinemia
Show all 25Show fewer
  • Hairy cell leukemia
  • Small lymphocytic lymphoma / chronic lymphocytic leukemia (SLL/CLL)
  • Low grade B-cell lymphoma, unspecified
  • Nodular lymphocyte-predominant Hodgkin lymphoma
  • Poor-risk small lymphocytic lymphoma or chronic lymphocytic leukemia, defined by a 17p deletion, 11q deletion, or histologic conversion (if histologic conversion, PR or CR is required)
  • Aggressive B-cell non-Hodgkin's lymphoma that has failed at least one prior regimen of multiagent chemotherapy, is in PR (partial remission) or CR (complete remission), and patient is either ineligible for autologous hematopoietic BMT or autologous BMT is not recommended:
  • Follicular grade 3 lymphoma
  • Histoconversion of low-grade B-cell lymphoma (including SLL/CLL) to aggressive B-cell non-Hodgkin's lymphoma
  • Mantle cell lymphoma
  • Diffuse large B-cell lymphoma (excluding primary CNS [central nervous system] lymphoma)
  • "Gray zone" or composite lymphomas with combined features of primary mediastinal large B-cell and Hodgkin's lymphoma
  • Burkitt's lymphoma/leukemia
  • Atypical Burkitt's lymphoma/leukemia (high grade B-cell lymphoma, unclassified, including that with features intermediate between Burkitt's and diffuse large B-cell lymphoma)
  • Must have a related donor who is at least HLA haploidentical
  • Any previous BMT must have occurred at least 3 months prior
  • Left ventricular ejection fraction at least 35%
  • Bilirubin no more than 3.0 mg/dL (unless due to Gilbert's syndrome), and ALT (alanine aminotransferase) and AST (aspartate aminotransferase) no more than 5 x upper limit of normal
  • FEV1 (forced expiratory volume in one second) and FVC (forced vital capacity) at least 40% of predicted
  • Absence of uncontrolled infection

Who cannot join

  • More than 20% involvement of bone marrow by chronic lymphocytic leukemia
  • Active central nervous system lymphoma
  • ECOG (Eastern Cooperative Oncology Group) performance status greater than 1 (2,3, and 4)
  • HIV positive
  • Pregnant or breastfeeding

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    Baltimore, Maryland, 21231

Other trials in United States

About this study

Official title: Nonmyeloablative BMT With Post-transplant Cyclophosphamide, Rituximab and Optimized Donor Selection for B-cell Lymphomas

This phase II trial is studying how well giving fludarabine and cyclophosphamide together with total-body irradiation and rituximab works in treating patients with B-cell lymphoma or chronic lymphocytic leukemia who are undergoing an allogeneic (donor) bone marrow transplant. The type of bone marrow transplant is a less intensive or "mini" transplant using a relative as the bone marrow donor. The donated bone marrow stem cells may replace the patient's immune system cells and help destroy any remaining cancer (graft-versus-tumor effect). Patients undergoing this type of transplant often have more than one relative who could be a donor. The trial is also studying a new way of choosing amongst possible donors which might improve how the rituximab works.

Read the detailed description

This phase II for relapsed or refractory B-cell malignancies builds on the platform of nonmyeloablative, related-donor, HLA (human leukocyte antigen)-matched or HLA-haploidentical BMT with post-transplantation high-dose cyclosphosphamide administered for prophylaxis of graft-versus-host disease and graft rejection. Rituximab is added to the transplant regimen with the goal of augmenting anti-tumor activity. In patients with B-cell lymphomas, specific polymorphisms in the immunoglobulin Fc receptor have been associated with greater sensitivity to rituximab or rituximab-based therapies, translating in some series into higher response rates and improved progression-free survival. This raises the possibility of selecting donors who carry this permissive polymorphism. This trial identifies and selects donors who have the favorable polymorphism at FcgammaR3A-158, thereby potentially conferring greater sensitivity to rituximab in the host after BMT.

Being tested
Fludarabine, Cyclophosphamide, Total body irradiation, Tacrolimus, Mycophenolate Mofetil
Keywords
lymphoma, non hodgkin lymphoma, allogeneic, bone marrow transplantation, nonmyeloablative, cyclophosphamide, rituximab
Medical subject headings
Lymphoma, Lymphoma, B-Cell, Lymphoma, Non-Hodgkin, Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

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

  • FludarabineDrug

    Also called Fludara

    Days -6 through -2: 30 mg/m^2 IV daily

  • CyclophosphamideDrug

    Also called Cytoxan, CTX, Cy

    Days -6 and -5: 14.5 mg/kg IV daily; Days 3 and 4: 50 mg/kg IV daily

  • Total body irradiationRadiation

    Also called TBI

    Day -1: 200 centigray (cGy) in a single fraction

  • TacrolimusDrug

    Also called FK-506, FK506, Prograf

    Start on Day 5 through Day 180

  • Mycophenolate MofetilDrug

    Also called MMF, CellCept

    Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)

  • RituximabDrug

    Also called Rituxan

    Day 30 and every week after for 8 total doses: 375 mg/m^2 IV

  • Allogeneic Bone Marrow Transplant (BMT)Biological

    Day 0: Donor bone marrow infusion

Study groups in NCT00946023
Study groupRoleWhat they receive
TransplantExperimentalNon-myeloablative allogeneic bone marrow transplant (BMT) with a fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD (graft vs host disease) prophylaxis. Rituximab will be given as post-transplant maintenance.
Receives: Drug: Fludarabine; Drug: Cyclophosphamide; Radiation: Total body irradiation; Drug: Tacrolimus; Drug: Mycophenolate Mofetil; Drug: Rituximab; Biological: Allogeneic Bone Marrow Transplant (BMT)

What is being measured

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

  1. Progression-free Survival

    Percentage of participants alive and without relapse or disease progression.

    Measured: 1 year post-intervention

Secondary outcomes (11)

  1. Progression-free Survival

    Percentage of participants alive with and without relapse.

    Measured: 2 years post-intervention

  2. Overall Survival

    Percentage of participants alive.

    Measured: 1 year post intervention

  3. Overall Survival

    Percentage of participants alive.

    Measured: 2 years post intervention

  4. Relapse

    Percentage of participants alive with relapse or disease progression.

    Measured: 1 year post intervention

  5. Relapse

    Percentage of participants alive with relapse or disease progression.

    Measured: 2 years post intervention

  6. Non-relapse Mortality

    Percentage of participants who died due to BMT-related reasons.

    Measured: 1 year post intervention

  7. Incidence of Grades II-IV Acute Graft-versus-Host-Disease (GVHD)

    Percentage of participants who experienced grade II, III, or IV acute GVHD. Acute GVHD is graded using the Przepiorka criteria.

    Measured: 1 year post intervention

  8. Incidence of Grades III-IV Acute GVHD

    Percentage of participants who experienced grade II, III, or IV acute GVHD. Acute GVHD is graded using the Przepiorka criteria.

    Measured: 1 year post intervention

  9. Incidence of Chronic GVHD

    Percentage of participants who experienced chronic GVHD. Chronic GVHD is graded using NIH consensus criteria and Seattle criteria.

    Measured: 1 year post intervention

  10. Engraftment

    Percentage of patients who engrafted neutrophils and platelets.

    Measured: Day 60

  11. Graft Failure

    Percentage of participants who failed to engraft.

    Measured: Day 60

Timeline

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

  1. First posted24 Jul 2009 (estimated)
  2. Study startJul 2009
  3. Primary completionJul 2013
  4. Study completion17 Jul 2013

Why it stopped: Funding was unavailable to complete the study as originally planned.

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
135 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00946023
Sponsor's protocol ID
J0941
Other IDs
NA_00025589
Status last verified
Jul 2018
First submitted
21 Jul 2009
Last updated
27 Aug 2018
Data monitoring committee
Yes

Publications

  • Kanakry JA, Gocke CD, Bolanos-Meade J, Gladstone DE, Swinnen LJ, Blackford AL, Fuchs EJ, Huff CA, Borrello I, Matsui WH, Brodsky RA, Rosner GL, Shanbhag S, Luznik L, Jones RJ, Ambinder RF, Kasamon YL. Phase II Study of Nonmyeloablative Allogeneic Bone Marrow Transplantation for B Cell Lymphoma with Post-Transplantation Rituximab and Donor Selection Based First on Non-HLA Factors. Biol Blood Marrow Transplant. 2015 Dec;21(12):2115-2122. doi: 10.1016/j.bbmt.2015.07.012. Epub 2015 Jul 14.

    PubMed 26183076

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Fludarabine, Cyclophosphamide and Total body irradiation in people with Lymphoma and B-cell Lymphoma, 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 25 inclusion and 5 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: stopped early, as of the sponsor's last update on 27 Aug 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Jul 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Progression-free Survival (time frame: 1 year post-intervention). 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 NCT00946023, 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 27 Aug 2018.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in