HIV Antigen-specific T-cells Targeting Conserved Epitopes (HST-NEETs) BMTCTN1903

NCT ID: NCT04975698

Last Updated: 2025-10-01

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-25
• Study Completion Date: 2026-06-30

Brief Summary

This is a Phase II multi-center trial single arm trial of autologous transplantation (ASCT) followed by administration of HST-NEETs for treatment of HIV associated lymphoma

Detailed Description

Eligible participants will have 100-120 mL of peripheral blood or 80-100 mL of MNCs via apheresis collected and shipped to Children's National Hospital at ambient temperature. The sample will be used to manufacture the HST-NEET product. The autologous peripheral blood stem cell graft suitable for rescue following conditioning will be obtained either before or after the collection of blood to generate HST-NEETs. Pre-transplant conditioning will consist of BEAM; BCNU 300 mg/m^2 on Day -6, Etoposide 100 mg/m^2 BID and Ara-C 100 mg/m2 BID on Days -5, -4, -3 and -2 and Melphalan 140 mg/m2 on Day -1. ASCT on Day 0. If the mobilized graft contains greater than 5.0 x 106 CD34+ cells per kg, any additional cells should be cryopreserved as a "back-up" graft in the event of graft failure related to the HST-NEETs. Participants will receive one dose (2 x 107 cells/m^2 ) of HST-NEETs between Days +3 to +7 based on the clinical condition of the participant. If this window is missed, the HST-NEETs may be administered up to Day +30 post-ASCT. Participants will be followed for at least one year after ASCT.

Conditions

HIV Associated Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

HST-NEETs

HIV+ Participants that were treated with autologous hematopoietic stem cell transplant.

Group Type: OTHER

HST-NEETs

Intervention Type: BIOLOGICAL

HST-NEETs are manufactured from an autologous peripheral blood or MNCs via apheresis collection and will be administered as a single intravenous (IV) infusion of 2x10\^7/m\^2 cells between 3 Days and 7 Days post-ASCT.

Bone Marrow Transplant

Intervention Type: BIOLOGICAL

Day 0 is the day of bone marrow transplantation.

Interventions

HST-NEETs

HST-NEETs are manufactured from an autologous peripheral blood or MNCs via apheresis collection and will be administered as a single intravenous (IV) infusion of 2x10\^7/m\^2 cells between 3 Days and 7 Days post-ASCT.

Intervention Type: BIOLOGICAL

Bone Marrow Transplant

Day 0 is the day of bone marrow transplantation.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Age 15 years old or older at time of enrollment.

2. Receiving antiretroviral therapies (ART) with HIV viral load < 200 copies or below the limit of detection by standard commercial assay. An HIV-1 RNA measurement that is ≥ 200 copies measured by an FDA-approved commercial assay but <500 copies may be allowed if this is followed by an HIV-1 RNA measurement below the limit of detection or if an exception is approved.

3. Diagnosis of refractory or recurrent diffuse large B-cell lymphoma, composite lymphoma with greater than 50% diffuse large B-cell lymphoma, mediastinal B-cell lymphoma, immunoblastic, plasmablastic, Burkitt or high grade B cell lymphoma or classical Hodgkin lymphoma. Participants with aggressive B-cell lymphoma that is transformed from follicular lymphoma are eligible for the study, pending fulfillment of other criteria.

4. Plan to treat participant with high dose chemotherapy and autologous hematopoietic stem cell transplantation (ASCT).

5. All participants must have chemosensitive disease as demonstrated by at least a partial response (as defined by the criteria in Chapter 3) to induction or salvage therapy.

6. Absolute Lymphocyte Count (ALC) greater than or equal to 800/µL. If ALC is less than 800/uL but still above 400/uL patient may be eligible if the HST-NEETs manufacturing blood product is collected via non-mobilized leukapheresis(apheresis).

7. Participants with adequate organ function as measured by:

1. Cardiac: Participants must have a left ventricular ejection fraction at rest greater than or equal to 40% demonstrated by MUGA or echocardiogram.

2. Hepatic:

i. Bilirubin less than or equal to 2.0 mg/dL (except for isolated hyperbilirubinemia attributed to Gilbert syndrome or antiretroviral therapy as specified in Appendix D) and ALT and AST less than or equal to 3x the upper limit of normal. ii. Concomitant Hepatitis: Participants with chronic hepatitis B or C may be enrolled on the trial providing the above criteria are met. In addition, they must not have evidence of active viral replication by PCR, and no clinical or pathologic evidence of irreversible chronic liver disease. c) Renal: Creatinine clearance (calculated creatinine clearance is permitted based on institutional practice) greater than 40 mL/min.

d) Pulmonary DLCO (corrected for hemoglobin), FEV1, FVC greater than or equal to 45% of predicted.

8. Voluntary written consent or assent obtained prior to enrollment on study with the understanding that consent or assent may be withdrawn by the participant at any time without prejudice to future medical care.

Exclusion Criteria

1. Karnofsky performance score less than 70%.

2. Participant is known to have an HIV subtype other than B.

3. Participant has documented raltegravir or protease inhibitor resistance.

4. Myocardial infarction within 6 months prior to enrollment or New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia.

5. Uncontrolled bacterial, viral or fungal infection (currently taking medication and with progression or no clinical improvement).

6. Participant has active CNS involvement.

7. Participants with prior malignancies except resected non-melanoma skin cancer or treated cervical carcinoma in situ. Cancer treated with curative intent greater than or equal to 5 years previously will be allowed. Cancer treated with curative intent less than 5 years BMT CLINICAL TRIALS NETWORK HIV T-Cell - Protocol 1903 Version 1.0 Dated February 24, 2021 2-4 Confidential previously may be eligible must be reviewed and approved by the Protocol Officer or Chairs.

8. Female participants that are pregnant as per institutional definition or breastfeeding.

9. Fertile men or women unwilling to use contraceptive techniques from the time of initiation of mobilization until six-months post-transplant.

10. Prior autologous or allogeneic HCT, or prior therapy with chimeric antigen receptor (CAR) T-cells.

11. Participants with evidence of MDS/AML or abnormal cytogenetic analysis indicative of MDS on the pre-transplant bone marrow examination. Pathology report documentation need not be submitted.

12. Steroids greater than 0.5 mg/kg/day prednisone equivalents.

13. Bone marrow involvement by lymphoma at time of workup. Prior history of bone marrow involvement is allowed if cleared prior to ASCT.

• Minimum Eligible Age: 15 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Blood and Marrow Transplant Clinical Trials Network

NETWORK

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

National Marrow Donor Program

OTHER

Sponsor Role: collaborator

Children's National Research Institute

OTHER

Sponsor Role: collaborator

Catherine Bollard

NIH

Sponsor Role: lead

Responsible Party

Catherine Bollard

Primary Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Steve Devine, MD, MS

Role: STUDY_CHAIR

National Marrow Donor Program

Locations

City of Hope National Medical Center

Duarte, California, United States

Georgetown

Washington D.C., District of Columbia, United States

H. Lee Moffitt Cancer Center

Tampa, Florida, United States

Northside

Atlanta, Georgia, United States

University of Illinois

Chicago, Illinois, United States

Johns Hopkins University

Baltimore, Maryland, United States

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Memorial Sloan Kettering (MSKCC)

New York, New York, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Baylor College of Medicine

Houston, Texas, United States

MD Anderson

Houston, Texas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form: Assent to Participate in Research

View Document

Document Type: Informed Consent Form: Informed Consent to Participate in Research

View Document

Related Links

https://bmtctn.net/

Blood and Marrow Transplant Clinical Trials Network Website

Other Identifiers

2U10HL069294-11

Identifier Type: NIH

Identifier Source: secondary_id

View Link

BMTCTN1903

Identifier Type: -

Identifier Source: org_study_id