B-Cell Lymphoid MalignanciesPhase 2NCT04684979
Transplantation of Hematopoietic Stem Cells From HLA-compatible Donors in Patients With B-Cell Lymphoid Malignancies
A Phase 2 study testing Hematopoietic Stem Cells from HLA-compatible Related and Hematopoietic Stem Cells from HLA Unrelated in people with B-Cell Lymphoid Malignancies and Hematologic Malignancy, run by Baptist Health South Florida at 1 site in United States.
Trial summary
This research study is being conducted to treat patients with B-cell lymphoid malignancies. These types of cancers include diffuse large cell (DLBCL) non-Hodgkin's lymphoma (NHL), mantle cell NHL, any indolent B cell NHL (such as follicular, small cell or marginal zone NHL), or chronic lymphocytic leukemia (CLL). Read more about this study
- Who is it for?
- Ages 18 to 74 years
- Conditions the study is for
- B-Cell Lymphoid Malignancies, Hematologic Malignancy, Non-Hodgkin Lymphoma
- What is being tested?
- Hematopoietic Stem Cells from HLA-compatible Related and Hematopoietic Stem Cells from HLA Unrelated
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Mar 2022to Mar 2027
- Phase
- Phase 2
- 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 18 to 74 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- :
- Patients aged 18-74 years at initial referral with a suitably matched related or unrelated donor who have provided their informed consent to participate in the clinical trial.
- If post-pubertal, females agree to take hormonal therapy to suppress menses unless a specific contra-indication to estrogen exists
- Diagnosis:
- Patients with CD20+ aggressive B cell NHL (DLBCL, large cell transformation of indolent NHL/CLL, or mantle cell) OR CD20+ indolent NHL/CLL. Relapsed disease must be biopsy proven and CD20 positivity must be demonstrated within the 12 months prior to protocol enrollment.
- Eligible patients with DLBCL NHL will:
Show all 31Show fewer
- have relapsed disease following initial therapy but failed to mobilize or had bone marrow involvement and therefore are not suitable for an autologous transplant OR
- have high-intermediate or high-risk second-line age-adjusted International Prognostic Index score and be in 2nd CR/PR following an autologous transplant OR
- have failed an autologous transplant and be in PR or better after salvage chemotherapy.
- Eligible patients with transformed indolent NHL/CLL will:
- have CR/PR of the large cell component of their disease after either salvage chemotherapy or an autologous transplant.
- Eligible patients with mantle cell NHL will:
- be high-risk such as p53 positivity and be in 1st CR/PR after initial therapy OR
- have relapsed disease following initial therapy and be in 2nd or 3rd CR/PR after salvage chemotherapy.
- Eligible patients with indolent B cell NHL (such as, but not limited to, follicular, small cell or marginal zone NHL) or CLL will:
- have 1st or subsequent progression or primary refractory disease (pre-allograft cytoreduction necessary but CR/PR not required).
- Pre-allograft Salvage Chemotherapy:
- This can include a single autologous transplant using high dose chemotherapy conditioning if appropriate OR ≥ 2 cycles of intensive combination chemotherapy (e.g. RICE) as appropriate according to diagnosis and prior therapy.
- CLL patients who have received CAMPATH do not have to receive pre-allograft salvage chemotherapy.
- Timing of PBSCT:
- Admission for PBSCT must be within 120 days of autologous transplantation OR 80 days of the last cycle of chemotherapy.
- Organ Function and Performance Status Criteria:
- Karnofsky score ≥ 70 %
- calculated creatinine clearance ≥ 50 mL/min OR if creatinine ≥ 1.2, a history of renal dysfunction, age > 50 years, prior transplant, and/or a single kidney, the patient must have a measured creatinine clearance (using 24 hour urine collection) ≥ 50 mL/min
- bilirubin < 2.5, AST/ALT ≤ 3 x upper limit of normal (unless benign congenital hyperbilirubinemia)
- pulmonary function (spirometry and corrected DLCO) ≥ 50% normal
- left ventricular ejection fraction ≥ 40%
- albumin ≥ 2.5. Donor HLA-compatible related donors
- Patients who have an HLA-matched or one allele mismatched related donor are eligible for entry on this protocol. This will include a healthy related donor who is genotypically or phenotypically matched at least 9/10 of the A, B, C, DRB1, and DQB1 loci, as tested by high resolution.
- HLA-compatible Unrelated donors • Patients who do not have a related HLA-matched donor but have an unrelated donor who is matched at
- ≥ 9/10 (allele mismatch only) of the A, B, C, DRB1, and DQB1 loci, as tested by high resolution.
Who cannot join
- Diagnosis: known negativity for CD20 pre-allograft; mantle cell or DLBCL NHL with progressive disease at allograft work-up
- Prior Therapy: prior allogeneic transplant (prior autologous transplant is acceptable)
- Cytoreduction and timing of NMA PBSCT: patients unable to complete planned cytoreduction due to therapy complications, or who undergo cytoreduction but are unable to proceed to allografting within the defined time period, are ineligible for allograft on protocol
- Active and uncontrolled infection at time of transplantation including active infection with Aspergillus or other mold, or HIV infection
- Patients positive for Hepatitis B or C at risk for viral reactivation.
- Inadequate performance status/organ function
- Pregnant or breast feeding
- Patient or guardian unable to give informed consent or unable to comply with the treatment protocol including appropriate supportive care, follow-up and research tests.
Trial locations and contacts
1 site in 1 country.
United States1 site
Miami Cancer Institute at Baptist Health of South Florida
Miami, Florida, 33176
About this study
Official title: A Non-Myeloablative Conditioning Regimen With Peri-Transplant Rituximab and the Transplantation of Hematopoietic Stem Cells From HLA-compatible Related or Unrelated Donors in Patients With B-Cell Lymphoid Malignancies
This research study is being conducted to treat patients with B-cell lymphoid malignancies. These types of cancers include diffuse large cell (DLBCL) non-Hodgkin's lymphoma (NHL), mantle cell NHL, any indolent B cell NHL (such as follicular, small cell or marginal zone NHL), or chronic lymphocytic leukemia (CLL). Patients with these types of lymphomas have been shown to benefit from peripheral blood stem cell transplantation (PBSCT). PBSCT uses healthy blood stem cells from a donor to replace your diseased or damaged bone marrow. Before undergoing PBSCT, you'll receive chemotherapy and/or radiation to destroy your diseased cells and prepare your body for the donor cells. This is called a "conditioning regimen." Non-myeloablative (NMA) conditioning causes minimal cell death. This research study will look at a course of treatment using NMA conditioning regimen including low dose chemotherapy and low dose radiation as well as rituximab and PBSCT from a compatible donor. The primary aim is to obtain a preliminary estimate of the overall and event-free survival 1 year post-transplant after NMA.
Read the detailed description
This is a phase 2 study of a treatment regimen consisting of a non-myeloablative (NMA) conditioning regimen incorporating low dose chemotherapy and low dose radiation as well as peri-transplant Rituximab and the transplantation of peripheral blood stem cells (PBSC) from an HLA compatible related or unrelated donor in patients with B cell lymphoid malignancies including diffuse large cell (DLBCLC) and mantle cell non-Hodgkin's lymphoma (MCL), indolent B cell NHL, or chronic lymphocytic leukemia (CLL). The study design will be based on a total of 90 patients, 30 recipients of related matched and 60 recipients of mismatched related or unrelated PBSCT.
It is anticipated that the accrual will last 5-6 years. At the conclusion of the study, the safety and a preliminary assessment of efficacy of NMA PBSCT will be determined. The treatment will be declared efficacious if the disease-free survival at 1 year in this patient population is at least 50%.
- Being tested
- Hematopoietic Stem Cells from HLA-compatible Related, Hematopoietic Stem Cells from HLA Unrelated
- Keywords
- Hematologic Malignancies, NHL
- Medical subject headings
- Hematologic Neoplasms, Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hematopoietic Stem Cells from HLA-compatible RelatedBiological
NMA PBSCT (Non-Myeloablative peripheral blood stem cell transplantation) incorporating rituximab and utilizing PBSC (Peripheral blood stem cells) to increase graft cell dose in patients with selected B lymphoid malignancies.
Hematopoietic Stem Cells from HLA UnrelatedBiological
NMA PBSCT (Non-Myeloablative peripheral blood stem cell transplantation) incorporating rituximab and utilizing PBSC (Peripheral blood stem cells) to increase graft cell dose in patients with selected B lymphoid malignancies.
| Study group | Role | What they receive |
|---|---|---|
| HLA-compatible Related Donor | Experimental | This is a phase 2 study to evaluate NMA PBSCT incorporating peri-transplant rituximab and utilizing PBSC to augment graft cell dose in patients with selected B lymphoid malignancies. Salvage chemotherapy will be required as part of transplant eligibility, both to achieve debulking of disease to allow sufficient time for the development of a post-transplant GVL effect, and to contribute to recipient immune suppression and thus facilitate donor engraftment. Receives: Biological: Hematopoietic Stem Cells from HLA-compatible Related |
| Unrelated Donor | Experimental | This is a phase 2 study to evaluate NMA PBSCT incorporating peri-transplant rituximab and utilizing PBSC to augment graft cell dose in patients with selected B lymphoid malignancies. Salvage chemotherapy will be required as part of transplant eligibility, both to achieve debulking of disease to allow sufficient time for the development of a post-transplant GVL effect, and to contribute to recipient immune suppression and thus facilitate donor engraftment. Receives: Biological: Hematopoietic Stem Cells from HLA Unrelated |
What is being measured
The primary outcome is the main question the study is designed to answer.
Estimate the overall and event-free survival
The primary aim of this study is to obtain a preliminary estimate of the overall and event-free survival at 1 year after NMA PBSCT with peri-transplant rituximab using an HLA matched or single HLA allele disparate related or unrelated donors
Measured: 1 year
Secondary outcomes (9)
Speed of Recovery Post Allograft
the speed of neutrophil and platelet recovery post allograft
Measured: 100 days
Response to Engraftment
the incidence and speed of donor-derived engraftment
Measured: 100 days
Status of Graft Versus Host Disease
The incidence and severity of acute GVHD(Graft Versus Host Disease) at 100 days
Measured: 100 days
Number of Participants with Graft Versus Host Disease
The incidence and severity of chronic GVHD (Graft Versus Host Disease) at 1 year
Measured: 1 year
Number of Participants with Complications
the incidence of serious infectious complications with their correlation with laboratory measurements of immune recovery
Measured: 100 days
Response Rate to Vaccination
the response to vaccination after PBSCT (Peripheral Blood Stem Cells Transplantation)
Measured: 100 days
Number of Transplant Related Mortality Incidences
the incidence of Transplant Related Mortality at 100 and 180 days
Measured: 100 and 180 days
Number of Relapse or Disease Progression Instances
the incidence of malignant relapse or disease progression at 1 and 2 years
Measured: 1 and 2 years
Number of Overall and Event Free Survival
the probabilities of overall and event-free survival at 2 years after Peripheral Blood Stem Cells Transplantation
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Dec 2020
- Study start28 Mar 2022
- Primary completionMar 2026 (estimated)
- Study completionMar 2027 (estimated)
Why it stopped: The landscape of treatment for patients targeted for enrollment has significantly changed since the protocol was written and approved, and the research treatment is no longer the best option for this population.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for B-Cell Lymphoid MalignanciesStudies 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
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- The study design will be based on a total of 90 patients, 30 recipients of related matched and 60 recipients of mismatched related or unrelated PBSCT.
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baptist Health South Florida
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Guenther Koehne, MD, PhD, Principal investigator, Miami Cancer Institute at Baptist Health of South Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04684979
- Sponsor's protocol ID
- 2019-KOE-002
- Status last verified
- Oct 2023
- First submitted
- 22 Dec 2020
- Last updated
- 1 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Non-Myeloablative Conditioning Regimen With Peri-Transplant Rituximab and the Transplantation of Hematopoietic Stem Cells From HLA-compatible Related or Unrelated Donors in Patients With B-Cell Lymphoid Malignancies
- ClinicalTrials.gov ID
- NCT04684979
- Acronym / sponsor ID
- 2019-KOE-002
- Keywords
- Hematologic Malignancies, NHL
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The landscape of treatment for patients targeted for enrollment has significantly changed since the protocol was written and approved, and the research treatment is no longer the best option for this population.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Baptist Health South FloridaUniversity, hospital or other
- Study start
- 28 Mar 2022 (actual)
- Primary completion
- Mar 2026 (estimated)
- Study completion
- Mar 2027 (estimated)
- First posted
- 28 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research study is being conducted to treat patients with B-cell lymphoid malignancies. These types of cancers include diffuse large cell (DLBCL) non-Hodgkin's lymphoma (NHL), mantle cell NHL, any indolent B cell NHL (such as follicular, small cell or marginal zone NHL), or chronic lymphocytic leukemia (CLL). Patients with these types of lymphomas have been shown to benefit from peripheral blood stem cell transplantation (PBSCT). PBSCT uses healthy blood stem cells from a donor to replace your diseased or damaged bone marrow. Before undergoing PBSCT, you'll receive chemotherapy and/or radiation to destroy your diseased cells and prepare your body for the donor cells. This is called a "conditioning regimen." Non-myeloablative (NMA) conditioning causes minimal cell death. This research study will look at a course of treatment using NMA conditioning regimen including low dose chemotherapy and low dose radiation as well as rituximab and PBSCT from a compatible donor. The primary aim is to obtain a preliminary estimate of the overall and event-free survival 1 year post-transplant after NMA.
Detailed description
This is a phase 2 study of a treatment regimen consisting of a non-myeloablative (NMA) conditioning regimen incorporating low dose chemotherapy and low dose radiation as well as peri-transplant Rituximab and the transplantation of peripheral blood stem cells (PBSC) from an HLA compatible related or unrelated donor in patients with B cell lymphoid malignancies including diffuse large cell (DLBCLC) and mantle cell non-Hodgkin's lymphoma (MCL), indolent B cell NHL, or chronic lymphocytic leukemia (CLL). The study design will be based on a total of 90 patients, 30 recipients of related matched and 60 recipients of mismatched related or unrelated PBSCT.
It is anticipated that the accrual will last 5-6 years. At the conclusion of the study, the safety and a preliminary assessment of efficacy of NMA PBSCT will be determined. The treatment will be declared efficacious if the disease-free survival at 1 year in this patient population is at least 50%.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The study design will be based on a total of 90 patients, 30 recipients of related matched and 60 recipients of mismatched related or unrelated PBSCT.
| Arm | Type | Receives |
|---|---|---|
| HLA-compatible Related Donor | Experimental | Biological: Hematopoietic Stem Cells from HLA-compatible RelatedThis is a phase 2 study to evaluate NMA PBSCT incorporating peri-transplant rituximab and utilizing PBSC to augment graft cell dose in patients with selected B lymphoid malignancies. Salvage chemotherapy will be required as part of transplant eligibility, both to achieve debulking of disease to allow sufficient time for the development of a post-transplant GVL effect, and to contribute to recipient immune suppression and thus facilitate donor engraftment. |
| Unrelated Donor | Experimental | Biological: Hematopoietic Stem Cells from HLA UnrelatedThis is a phase 2 study to evaluate NMA PBSCT incorporating peri-transplant rituximab and utilizing PBSC to augment graft cell dose in patients with selected B lymphoid malignancies. Salvage chemotherapy will be required as part of transplant eligibility, both to achieve debulking of disease to allow sufficient time for the development of a post-transplant GVL effect, and to contribute to recipient immune suppression and thus facilitate donor engraftment. |
Who may qualify
- Ages
- 18 to 74 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (31 listed)
- :
- Patients with CD20+ aggressive B cell NHL (DLBCL, large cell transformation of indolent NHL/CLL, or mantle cell) OR CD20+ indolent NHL/CLL. Relapsed disease must be biopsy proven and CD20 positivity must be demonstrated within the 12 months prior to protocol enrollment.
- have relapsed disease following initial therapy but failed to mobilize or had bone marrow involvement and therefore are not suitable for an autologous transplant OR
- have high-intermediate or high-risk second-line age-adjusted International Prognostic Index score and be in 2nd CR/PR following an autologous transplant OR
- have failed an autologous transplant and be in PR or better after salvage chemotherapy.
Key exclusion criteria (8 listed)
- Diagnosis: known negativity for CD20 pre-allograft; mantle cell or DLBCL NHL with progressive disease at allograft work-up
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 |
|---|---|---|
| Hematopoietic Stem Cells from HLA-compatible RelatedNMA PBSCT (Non-Myeloablative peripheral blood stem cell transplantation) incorporating rituximab and utilizing PBSC (Peripheral blood stem cells) to increase graft cell dose in patients with selected B lymphoid malignancies. | Biological | HLA-compatible Related Donor |
| Hematopoietic Stem Cells from HLA UnrelatedNMA PBSCT (Non-Myeloablative peripheral blood stem cell transplantation) incorporating rituximab and utilizing PBSC (Peripheral blood stem cells) to increase graft cell dose in patients with selected B lymphoid malignancies. | Biological | Unrelated Donor |
Primary outcome
Estimate the overall and event-free survival
Time frame: 1 year
The primary aim of this study is to obtain a preliminary estimate of the overall and event-free survival at 1 year after NMA PBSCT with peri-transplant rituximab using an HLA matched or single HLA allele disparate related or unrelated donors
9 secondary outcomes
Speed of Recovery Post Allograft
Time frame: 100 days
Response to Engraftment
Time frame: 100 days
Status of Graft Versus Host Disease
Time frame: 100 days
Number of Participants with Graft Versus Host Disease
Time frame: 1 year
Number of Participants with Complications
Time frame: 100 days
Response Rate to Vaccination
Time frame: 100 days
Number of Transplant Related Mortality Incidences
Time frame: 100 and 180 days
Number of Relapse or Disease Progression Instances
Time frame: 1 and 2 years
Number of Overall and Event Free Survival
Time frame: 2 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2023.
- Miami Cancer Institute WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Guenther Koehne, MD, PhD principal investigator
Miami Cancer Institute at Baptist Health of South Florida
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Hematopoietic Stem Cells from HLA-compatible Related and Hematopoietic Stem Cells from HLA Unrelated in people with B-Cell Lymphoid Malignancies and Hematologic Malignancy, run by Baptist Health South Florida 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 31 inclusion and 8 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: withdrawn, as of the sponsor's last update on 1 Nov 2023. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Estimate the overall and event-free survival (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Nov 2023.