## Protocol Section
### Identification Module
**NCT ID:** NCT04684979

**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

#### Organization Study ID Info
**ID:** 2019-KOE-002
#### Organization
**Class:** OTHER
**Full Name:** Baptist Health South Florida
### Status Module
#### Completion Date
**Date:** 2027-03

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2023-11-01

**Type:** ACTUAL

**Last Update Submit Date:** 2023-10-31

**Overall Status:** WITHDRAWN

#### Primary Completion Date
**Date:** 2026-03

**Type:** ESTIMATED

#### Start Date
**Date:** 2022-03-28

**Type:** ACTUAL

**Status Verified Date:** 2023-10

#### Study First Post Date
**Date:** 2020-12-28
**Type:** ACTUAL
**Study First Submit Date:** 2020-12-22
**Study First Submit QC Date:** 2020-12-22
**Why 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.
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Baptist Health South Florida

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Oversight Has DMC:** True

### Description Module

**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.

**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%.

### Conditions Module

**Conditions:**

- B-Cell Lymphoid Malignancies

- Hematologic Malignancy

- Non-Hodgkin Lymphoma

**Keywords:**

- Hematologic Malignancies, NHL

### Design Module

#### Design Info

**Allocation:** NON_RANDOMIZED

**Intervention Model:** PARALLEL

**Intervention 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 Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Type:** ACTUAL

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 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.

**Intervention Names:**

- Biological: Hematopoietic Stem Cells from HLA-compatible Related

**Label:** HLA-compatible Related Donor

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** 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.

**Intervention Names:**

- Biological: Hematopoietic Stem Cells from HLA Unrelated

**Label:** Unrelated Donor

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- HLA-compatible Related Donor

**Description:** 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.

**Name:** Hematopoietic Stem Cells from HLA-compatible Related

**Type:** BIOLOGICAL

#### Intervention 2

**Arm Group Labels:**

- Unrelated Donor

**Description:** 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.

**Name:** Hematopoietic Stem Cells from HLA Unrelated

**Type:** BIOLOGICAL

### Outcomes Module

#### Primary Outcomes

**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

**Measure:** Estimate the overall and event-free survival

**Time Frame:** 1 year

#### Secondary Outcomes

**Description:** the speed of neutrophil and platelet recovery post allograft

**Measure:** Speed of Recovery Post Allograft

**Time Frame:** 100 days

**Description:** the incidence and speed of donor-derived engraftment

**Measure:** Response to Engraftment

**Time Frame:** 100 days

**Description:** The incidence and severity of acute GVHD(Graft Versus Host Disease) at 100 days

**Measure:** Status of Graft Versus Host Disease

**Time Frame:** 100 days

**Description:** The incidence and severity of chronic GVHD (Graft Versus Host Disease) at 1 year

**Measure:** Number of Participants with Graft Versus Host Disease

**Time Frame:** 1 year

**Description:** the incidence of serious infectious complications with their correlation with laboratory measurements of immune recovery

**Measure:** Number of Participants with Complications

**Time Frame:** 100 days

**Description:** the response to vaccination after PBSCT (Peripheral Blood Stem Cells Transplantation)

**Measure:** Response Rate to Vaccination

**Time Frame:** 100 days

**Description:** the incidence of Transplant Related Mortality at 100 and 180 days

**Measure:** Number of Transplant Related Mortality Incidences

**Time Frame:** 100 and 180 days

**Description:** the incidence of malignant relapse or disease progression at 1 and 2 years

**Measure:** Number of Relapse or Disease Progression Instances

**Time Frame:** 1 and 2 years

**Description:** the probabilities of overall and event-free survival at 2 years after Peripheral Blood Stem Cells Transplantation

**Measure:** Number of Overall and Event Free Survival

**Time Frame:** 2 years

### Eligibility Module

**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 Age:** 74 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Miami

**Country:** United States

**Facility:** Miami Cancer Institute at Baptist Health of South Florida

**State:** Florida

**Zip:** 33176

#### Overall Officials

**Official 1:**

**Affiliation:** Miami Cancer Institute at Baptist Health of South Florida

**Name:** Guenther Koehne, MD, PhD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

### References Module

#### See Also Links

**Label:** Miami Cancer Institute Website

**URL:** http://baptisthealth.net/cancer-care/home

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000006402

- Term: Hematologic Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC15

- Name: Blood and Lymph Conditions

- Abbrev: BC20

- Name: Immune System Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M11220

- Name: Lymphoma

- Relevance: LOW

- As Found: Unknown

- ID: M21314

- Name: Hematologic Neoplasms

- Relevance: HIGH

- As Found: Hematologic Malignancies

- ID: M9490

- Name: Hematologic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T3543

- Name: Lymphosarcoma

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000009369

- Term: Neoplasms

- ID: D000019337

- Term: Hematologic Neoplasms

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: ARhu

- Name: Antirheumatic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M373

- Name: Rituximab

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-24
