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

NCT04684979 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 2019-KOE-002
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

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

Keywords

Hematologic Malignancies, NHL

Outcome Measures

Primary Outcomes (1)

• 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

  1 year

Secondary Outcomes (9)

• Speed of Recovery Post Allograft

  100 days

• Response to Engraftment

  100 days

• Status of Graft Versus Host Disease

  100 days

• Number of Participants with Graft Versus Host Disease

  1 year

• Number of Participants with Complications

  100 days

Study Arms (2)

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.

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.

Biological: Hematopoietic Stem Cells from HLA Unrelated

Interventions

Hematopoietic Stem Cells from HLA-compatible Related BIOLOGICAL

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.

HLA-compatible Related Donor

Hematopoietic Stem Cells from HLA Unrelated BIOLOGICAL

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.

Unrelated Donor

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Baptist Health South Florida: lead

Study Sites (1)

Miami Cancer Institute at Baptist Health of South Florida

Miami, Florida, 33176, United States

Location

Related Links

• Miami Cancer Institute Website

MeSH Terms

Conditions

Hematologic Neoplasms; Lymphoma, Non-Hodgkin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoma; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Guenther Koehne, MD, PhD

  Miami Cancer Institute at Baptist Health of South Florida

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: December 22, 2020
• First Posted: December 28, 2020
• Study Start: March 28, 2022
• Primary Completion: March 1, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: November 1, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)