Description:
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
Title
- Brief Title: HIV Antigen-specific T-cells Targeting Conserved Epitopes (HST-NEETs)
- Official Title: Administration of HIV-specific T Cells to HIV+ Patients Receiving High Dose Chemotherapy Followed by Autologous Stem Cell Rescue - Auto -RESIST
Clinical Trial IDs
- ORG STUDY ID:
BMTCTN1903
- SECONDARY ID:
2U10HL069294-11
- NCT ID:
NCT04975698
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Busulfan | Busulfex | HST-NEETs |
Purpose
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 collected and shipped to
Children's National Hospital at ambient temperature. The peripheral blood 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/m2
on Day -6, Etoposide 100 mg/m2 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/m2 ) of HST-NEETs between Days +3 to +7 based on the clinical condition
of the participant (as outlined in Section 2.6). 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.
Trial Arms
Name | Type | Description | Interventions |
---|
HST-NEETs | Other | Participants will receive 2x107 /m2 cells as a single intravenous (IV) infusion. The cells will be cryopreserved ideally at 1x107 T cells per mL. | |
Eligibility Criteria
Eligible participants are HIV positive and plan to be treated by high dose chemotherapy
followed by an autologous stem cell transplant (ASCT). Participants are a minimum of 15
years of age with Karnofsky performance status greater than or equal to 70% that have
primary refractory or recurrent diffuse large B-cell, immunoblastic, plasmablastic, high
grade, Burkitt, primary effusion lymphoma, or classical Hodgkin lymphoma. Participants must
have received 2 or 3 prior treatment regimens, including an induction chemotherapy and 1 or
2 salvage regimens. Monoclonal antibody therapy and local radiation will not be counted as
prior therapies. Participants must have chemosensitive disease as demonstrated by complete
or partial response to induction or most recent salvage chemotherapy. Participants cannot
have had prior autologous, allogeneic HCT, or CART-cell therapy. Participants must initiate
conditioning therapy within 3 months of stem cell mobilization or bone marrow harvest.
Blood cell mobilization or bone marrow harvest will be carried out per institutional
guidelines. Participants may not have HIV refractory to pharmacologic therapy. Patients
must not have an uncontrolled infection. Participants must not have received previous
cellular therapy
Inclusion Criteria:
1. Age 15 years old or older at time of enrollment.
2. Receiving antiretroviral therapies (ART) with HIV viral load below the limit of
detection by standard commercial assay. A single plasma HIV-1 RNA measurement that is
≥ the limit of quantification of the FDA-approved commercial assay but
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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 15 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | The proportion of participants who can be treated with (HST-NEETs) within 1 week of ASCT in a cooperative multi-institutional setting and 2.) the efficacy of HSTNEETs in reducing the HIV intact proviral |
Time Frame: | 6 Months |
Safety Issue: | |
Description: | Feasibility is defined as a participant receiving HST-NEETs within 1 week post-ASCT; Efficacy will be measured by the reduction in intact proviral reservoir. |
Secondary Outcome Measures
Measure: | Progression-free survival |
Time Frame: | 6 Months and 1 Year |
Safety Issue: | |
Description: | Participants are considered a failure for this endpoint if they die or if they relapse/progress or receive anti-lymphoma therapy, other than post-transplant consolidative localized radiation (maximum 3 sites) to sites of prior bulk disease pre-transplant (greater than 3cm) |
Measure: | The incidence and severity of acute infusion related toxicities |
Time Frame: | 1 Year |
Safety Issue: | |
Description: | Acute infusion related toxicities are defined as toxicities related to the infusion of HST-NEETs that occur within 24 hours of the infusion. |
Measure: | Impact of therapy on the HIV intact proviral reservoir |
Time Frame: | 1 Year |
Safety Issue: | |
Description: | Impact on intact proviral reservoir will be assessed using the IPDA at 4-8 weeks prior to transplant and 12 months following ASCT |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Not yet recruiting |
Lead Sponsor: | Catherine Bollard |
Last Updated
August 20, 2021