B-cell Adult Acute Lymphoblastic LeukemiaPhase 2NCT00867529

Rituximab in Treating Patients Undergoing Donor Peripheral Blood Stem Cell Transplant for Relapsed or Refractory B-cell Lymphoma

A Phase 2 study testing rituximab, peripheral blood stem cell transplantation and nonmyeloablative allogeneic hematopoietic stem cell transplantation in people with B-cell Adult Acute Lymphoblastic Leukemia and B-cell Childhood Acute Lymphoblastic Leukemia, run by Fred Hutchinson Cancer Center 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

Who is it for?: Any age
Conditions the study is for: B-cell Adult Acute Lymphoblastic Leukemia, B-cell Childhood Acute Lymphoblastic Leukemia, B-cell Chronic Lymphocytic Leukemia
What is being tested?: rituximab, peripheral blood stem cell transplantation and nonmyeloablative allogeneic hematopoietic stem cell transplantation
Type of treatment: Injection or infusion, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 63 participants
Where: 1 siteUnited States
Study dates: Feb 2009to 26 Mar 2015
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 Any age
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

With a diagnosis of CD20-expressing B-cell malignancy of any histologic type or grade for whom non-myeloablative allogeneic transplant is considered an appropriate treatment option
Who are enrolled on a non-myeloablative allogeneic HCT protocol employing total-body irradiation (TBI)-based conditioning of =< 4.5 Gy, with or without fludarabine; this protocol may be used as an adjunct to the allogeneic arm of a tandem autologous/allogeneic transplant protocol, provided the allogeneic conditioning meets the above criteria
Receiving unmodified peripheral blood mononuclear cell graft products
With an appropriate related or unrelated donor; human leukocyte antigen (HLA)-haploidentical donors are excluded
Able to give informed consent (if >= 18 years of age), or with a legal guardian capable of giving consent (if < 18 years of age)

Who cannot join

Ineligible for non-myeloablative allogeneic HCT
Receiving an HLA-haploidentical allograft
Who are fertile but unwilling to use contraception during and for at least 12 months after HCT
Females who are pregnant or breast-feeding

Trial locations and contacts

1 site in 1 country.

United States1 site

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, 98109

Other trials in United States

About this study

Official title: Addition of Pre- and Post-Transplant Rituximab for Patients Undergoing Non-myeloablative Allogeneic Hematopoietic Cell Transplantation With Relapsed or Refractory CD20+ B-Cell Malignancies

This phase II trial studies giving rituximab before and after a donor peripheral blood stem cell transplant in patients with B-cell lymphoma that does not respond to treatment (refractory) or has come back after a period of improvement (relapsed). Monoclonal antibodies, such as rituximab, can interfere with the ability of cancer cells to grow and spread. Giving rituximab before and after a donor peripheral blood stem cell transplant may help stop cancer from coming back and may help keep the patient's immune system from rejecting the donor's stem cells.

Read the detailed description

PRIMARY OBJECTIVES:

To determine the effect of addition of peri-transplant rituximab on relapse rate at 18 months after non-myeloablative allogeneic hematopoietic cell transplant (HCT) for cluster of differentiation (CD)20+ B-cell malignancies.

SECONDARY OBJECTIVES:

To determine overall and progression-free survival and non-relapse mortality.

II. To determine the incidence and severity of acute and chronic graft-versus-host disease (GVHD).

III. To determine the rate of graft rejection and graft failure.

IV. To determine the time to engraftment.

To determine the incidence of serious adverse events with the addition of rituximab.

VI. To evaluate the pharmacokinetics of rituximab in the setting of non-myeloablative allogeneic HCT.

VII. To describe donor and host polymorphisms of the FC gamma receptor IIIa (FCg RIIIA) and CD32 and evaluate their impact on disease response and relapse.

OUTLINE:

Patients receive rituximab intravenously (IV), pre- and post-transplant, on days -3, 10, 24, and 38. Patients undergo donor peripheral blood stem cell transplant on day 0. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically for 18 months and then annually for 5 years.

Conditions: B-cell Adult Acute Lymphoblastic Leukemia, B-cell Childhood Acute Lymphoblastic Leukemia, B-cell Chronic Lymphocytic Leukemia, Childhood Burkitt Lymphoma, Childhood Diffuse Large Cell Lymphoma, Childhood Immunoblastic Large Cell Lymphoma
Being tested: rituximab, peripheral blood stem cell transplantation, nonmyeloablative allogeneic hematopoietic stem cell transplantation, pharmacological study, laboratory biomarker analysis
Medical subject headings: Leukemia, Lymphocytic, Chronic, B-Cell, Burkitt Lymphoma, Lymphoma, Large B-Cell, Diffuse, Intraocular Lymphoma, Lymphoma, B-Cell, Marginal Zone, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Lymphoma, Non-Hodgkin, Hodgkin Disease

What participants receive

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

rituximabBiological
Also called IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8
Given IV
peripheral blood stem cell transplantationProcedure or surgery
Also called PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell
Undergo nonmyeloablative allogeneic peripheral blood/hematopoietic stem cell transplantation
nonmyeloablative allogeneic hematopoietic stem cell transplantationProcedure or surgery
Undergo nonmyeloablative allogeneic peripheral blood/hematopoietic stem cell transplantation
pharmacological studyOther
Also called pharmacological studies
Correlative studies
laboratory biomarker analysisOther
Correlative studies

Study groups in NCT00867529
Study group	Role	What they receive
Treatment (rituximab pre- and post-transplant)	Experimental	Patients receive rituximab IV, pre- and post-transplant, on days -3, 10, 24, and 38. Patients undergo donor peripheral blood stem cell transplant on day 0. Treatment continues in the absence of disease progression or unacceptable toxicity. Receives: Biological: rituximab; Procedure: peripheral blood stem cell transplantation; Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation; Other: pharmacological study; Other: laboratory biomarker analysis

What is being measured

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

Disease Relapse Rate
Number of patients with relapsed/progressive disease post-transplant. The effectiveness of pre- and post-transplant rituximab in decreasing the rate of relapse will be evaluated.
Measured: At 18 months

Secondary outcomes (4)

Incidence and Severity of Acute and Chronic GVHD Evaluated Per an Adapted Version of Common Terminology Criteria for Adverse Events (CTCAE) Version 2.0
Number of patients who developed acute/chronic GVHD post-transplant. A chronic GVHD diagnosis ≥1 manifestation that is distinctive for chronic GVHD, as opposed to acute GVHD.
aGVHD Stages
Skin:
a maculopapular eruption involving < 25% BSA a maculopapular eruption involving 25 - 50% BSA generalized erythroderma generalized erythroderma with bullous formation and often with desquamation
Liver:
bilirubin 2.0 - 3.0 mg/100 mL bilirubin 3 - 5.9 mg/100 mL bilirubin 6 - 14.9 mg/100 mL bilirubin > 15 mg/100 mL
Gut:
Diarrhea is graded 1 - 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as 1 in severity. The severity of gut involvement is assigned to the most severe involvement noted. Patients with visible bloody diarrhea are at least stage 2 gut and grade 3 overall.
aGVHD Grades Grade III: Stage 2 - 4 gut involvement and/or stage 2 - 4 liver involvement Grade IV: Pattern and severity of GVHD similar to grade 3 with extreme constitutional symptoms or death
Measured: Through day +100 after transplant
Overall Survival and Progression-free Survival
Number of patients surviving and number of patients surviving without progressive/relapsed disease, post-transplant.
Measured: At 6 months and then every year thereafter, up to 18 months
Rate of Graft Rejection and Graft Failure
Number of patients experiencing graft rejection and/or graft failure
Measured: 18 Months
Time to Engraftment
Median time from transplant to engraftment.
Measured: 18 Months

Timeline

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

Feb 200926 Mar 2015

First posted23 Mar 2009 (estimated)
Study startFeb 2009
Primary completionMar 2015
Study completion26 Mar 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for B-cell Adult Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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: 63 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00867529
Sponsor's protocol ID: 2226.00
Other IDs: NCI-2010-00107, 2226, 2226.00, P01CA078902, P30CA015704
Status last verified: Dec 2017
First submitted: 20 Mar 2009
Last updated: 2 Jan 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Shadman M, Maloney DG, Storer B, Sandmaier BM, Chauncey TR, Smedegaard Andersen N, Niederwieser D, Shizuru J, Bruno B, Pulsipher MA, Maziarz RT, Agura ED, Hari P, Langston AA, Maris MB, McSweeney PA, Storb R, Sorror ML. Rituximab-based allogeneic transplant for chronic lymphocytic leukemia with comparison to historical experience. Bone Marrow Transplant. 2020 Jan;55(1):172-181. doi: 10.1038/s41409-019-0660-8. Epub 2019 Sep 3.
PubMed 31481800

Study at a glance

From the registry record, last updated by the sponsor on 2 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Addition of Pre- and Post-Transplant Rituximab for Patients Undergoing Non-myeloablative Allogeneic Hematopoietic Cell Transplantation With Relapsed or Refractory CD20+ B-Cell Malignancies
ClinicalTrials.gov ID: NCT00867529
Acronym / sponsor ID: 2226.00
Conditions: B-cell Adult Acute Lymphoblastic Leukemia, B-cell Childhood Acute Lymphoblastic Leukemia, B-cell Chronic Lymphocytic Leukemia, Childhood Burkitt Lymphoma, Childhood Diffuse Large Cell Lymphoma, Childhood Immunoblastic Large Cell Lymphoma
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 63 participants (actual)
Lead sponsor: Fred Hutchinson Cancer CenterUniversity, hospital or other
Collaborators: American Cancer Society, Inc., National Cancer Institute (NCI)
Study start: Feb 2009
Primary completion: Mar 2015 (actual)
Study completion: 26 Mar 2015 (actual)
First posted: 23 Mar 2009 (estimated)
Results: Posted 22 May 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

PRIMARY OBJECTIVES:

To determine the effect of addition of peri-transplant rituximab on relapse rate at 18 months after non-myeloablative allogeneic hematopoietic cell transplant (HCT) for cluster of differentiation (CD)20+ B-cell malignancies.

SECONDARY OBJECTIVES:

To determine overall and progression-free survival and non-relapse mortality.

II. To determine the incidence and severity of acute and chronic graft-versus-host disease (GVHD).

III. To determine the rate of graft rejection and graft failure.

IV. To determine the time to engraftment.

To determine the incidence of serious adverse events with the addition of rituximab.

VI. To evaluate the pharmacokinetics of rituximab in the setting of non-myeloablative allogeneic HCT.

VII. To describe donor and host polymorphisms of the FC gamma receptor IIIa (FCg RIIIA) and CD32 and evaluate their impact on disease response and relapse.

OUTLINE:

After completion of study treatment, patients are followed up periodically for 18 months and then annually for 5 years.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Treatment (rituximab pre- and post-transplant)	Experimental	Biological: rituximab, Procedure: peripheral blood stem cell transplantation, Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation, Other: pharmacological study, Other: laboratory biomarker analysisPatients receive rituximab IV, pre- and post-transplant, on days -3, 10, 24, and 38. Patients undergo donor peripheral blood stem cell transplant on day 0. Treatment continues in the absence of disease progression or unacceptable toxicity.

Who may qualify

Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (5 listed)

With a diagnosis of CD20-expressing B-cell malignancy of any histologic type or grade for whom non-myeloablative allogeneic transplant is considered an appropriate treatment option
Who are enrolled on a non-myeloablative allogeneic HCT protocol employing total-body irradiation (TBI)-based conditioning of =< 4.5 Gy, with or without fludarabine; this protocol may be used as an adjunct to the allogeneic arm of a tandem autologous/allogeneic transplant protocol, provided the allogeneic conditioning meets the above criteria
Receiving unmodified peripheral blood mononuclear cell graft products
With an appropriate related or unrelated donor; human leukocyte antigen (HLA)-haploidentical donors are excluded
Able to give informed consent (if >= 18 years of age), or with a legal guardian capable of giving consent (if < 18 years of age)

Key exclusion criteria (4 listed)

Ineligible for non-myeloablative allogeneic HCT
Receiving an HLA-haploidentical allograft
Who are fertile but unwilling to use contraception during and for at least 12 months after HCT
Females who are pregnant or breast-feeding

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
rituximabAlso: IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8Given IV	Biological	Treatment (rituximab pre- and post-transplant)
peripheral blood stem cell transplantationAlso: PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cellUndergo nonmyeloablative allogeneic peripheral blood/hematopoietic stem cell transplantation	Procedure or surgery	Treatment (rituximab pre- and post-transplant)
nonmyeloablative allogeneic hematopoietic stem cell transplantationUndergo nonmyeloablative allogeneic peripheral blood/hematopoietic stem cell transplantation	Procedure or surgery	Treatment (rituximab pre- and post-transplant)
pharmacological studyAlso: pharmacological studiesCorrelative studies	Other	Treatment (rituximab pre- and post-transplant)
laboratory biomarker analysisCorrelative studies	Other	Treatment (rituximab pre- and post-transplant)

Primary outcome

Disease Relapse Rate
Time frame: At 18 months
Number of patients with relapsed/progressive disease post-transplant. The effectiveness of pre- and post-transplant rituximab in decreasing the rate of relapse will be evaluated.

4 secondary outcomes

Incidence and Severity of Acute and Chronic GVHD Evaluated Per an Adapted Version of Common Terminology Criteria for Adverse Events (CTCAE) Version 2.0
Time frame: Through day +100 after transplant
Overall Survival and Progression-free Survival
Time frame: At 6 months and then every year thereafter, up to 18 months
Rate of Graft Rejection and Graft Failure
Time frame: 18 Months
Time to Engraftment
Time frame: 18 Months

Results and safety

Results posted to the registry on 22 May 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Treatment (Rituximab Pre- and Post-transplant)	63	63

Primary outcome: Disease Relapse Rate

Time frame: At 18 months. Count of participants. Unit: Participants

Measure	Treatment (Rituximab Pre- and Post-transplant) n = 63
Value	18

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Treatment (Rituximab Pre- and Post-transplant)	5 of 63 (7.9%)	15 of 63 (23.8%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 Jan 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 31481800Shadman M, Maloney DG, Storer B, Sandmaier BM, Chauncey TR, Smedegaard Andersen N, Niederwieser D, Shizuru J, Bruno B, Pulsipher MA, Maziarz RT, Agura ED, Hari P, Langston AA, Maris MB, McSweeney PA, Storb R, Sorror ML. Rituximab-based allogeneic transplant for chronic lymphocytic leukemia with comparison to historical experience. Bone Marrow Transplant. 2020 Jan;55(1):172-181. doi: 10.1038/s41409-019-0660-8. Epub 2019 Sep 3.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

David Maloney principal investigator

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 5 inclusion and 4 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 2 Jan 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 22 May 2017). 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?

Disease Relapse Rate (time frame: At 18 months). 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 NCT00867529, 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 2 Jan 2018.