Clinical Trials /

Transplantation of Hematopoietic Stem Cells From HLA-compatible Donors in Patients With B-Cell Lymphoid Malignancies

NCT04684979

Description:

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.

Related Conditions:
  • B-Cell Non-Hodgkin Lymphoma
  • Chronic Lymphocytic Leukemia
  • Indolent Non-Hodgkin Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Transplantation of Hematopoietic Stem Cells From HLA-compatible Donors in Patients With B-Cell Lymphoid Malignancies
  • 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

Clinical Trial IDs

  • ORG STUDY ID: 2019-KOE-002
  • NCT ID: NCT04684979

Conditions

  • B-Cell Lymphoid Malignancies
  • Hematologic Malignancy
  • Non-Hodgkin Lymphoma

Interventions

DrugSynonymsArms
Hematopoietic Stem Cells from HLA-compatible RelatedHLA-compatible Related Donor
Hematopoietic Stem Cells from HLA UnrelatedUnrelated Donor

Purpose

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%.
    

Trial Arms

NameTypeDescriptionInterventions
HLA-compatible Related DonorExperimentalThis 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.
  • Hematopoietic Stem Cells from HLA-compatible Related
Unrelated DonorExperimentalThis 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.
  • Hematopoietic Stem Cells from HLA Unrelated

Eligibility Criteria

        Inclusion Criteria:

          -  :

               -  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:

          -  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.

        Exclusion Criteria:

          -  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.
      
Maximum Eligible Age:74 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Estimate the overall and event-free survival
Time Frame:1 year
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:Speed of Recovery Post Allograft
Time Frame:100 days
Safety Issue:
Description:the speed of neutrophil and platelet recovery post allograft
Measure:Response to Engraftment
Time Frame:100 days
Safety Issue:
Description:the incidence and speed of donor-derived engraftment
Measure:Status of Graft Versus Host Disease
Time Frame:100 days
Safety Issue:
Description:The incidence and severity of acute GVHD(Graft Versus Host Disease) at 100 days
Measure:Number of Participants with Graft Versus Host Disease
Time Frame:1 year
Safety Issue:
Description:The incidence and severity of chronic GVHD (Graft Versus Host Disease) at 1 year
Measure:Number of Participants with Complications
Time Frame:100 days
Safety Issue:
Description:the incidence of serious infectious complications with their correlation with laboratory measurements of immune recovery
Measure:Response Rate to Vaccination
Time Frame:100 days
Safety Issue:
Description:the response to vaccination after PBSCT (Peripheral Blood Stem Cells Transplantation)
Measure:Number of Transplant Related Mortality Incidences
Time Frame:100 and 180 days
Safety Issue:
Description:the incidence of Transplant Related Mortality at 100 and 180 days
Measure:Number of Relapse or Disease Progression Instances
Time Frame:1 and 2 years
Safety Issue:
Description:the incidence of malignant relapse or disease progression at 1 and 2 years
Measure:Number of Overall and Event Free Survival
Time Frame:2 years
Safety Issue:
Description:the probabilities of overall and event-free survival at 2 years after Peripheral Blood Stem Cells Transplantation

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Baptist Health South Florida

Trial Keywords

  • Hematologic Malignancies, NHL

Last Updated

December 28, 2020