Reduced Intensity Allogeneic HCT in Advanced Hematologic Malignancies w/T-Cell Depleted Graft

  • STATUS
    Recruiting
  • End date
    Jun 4, 2024
  • participants needed
    24
  • sponsor
    Stanford University
Updated on 4 November 2021
remission
fludarabine
tacrolimus
cyclophosphamide
hla-a
lymphoma
myelofibrosis
myelodysplastic syndromes
filgrastim
carbon monoxide
ejection fraction
granulocyte colony stimulating factor
melphalan
cell transplantation
leukemia
minimal residual disease
myeloproliferative syndromes
residual tumor
colony stimulating factor
human chorionic gonadotropin
Accepts healthy volunteers

Summary

Reduced intensity conditioning (RIC) has been increasingly adopted as a modality to allow preparative conditioning pre-transplant to be tolerated by older adults or those patients that are otherwise unfit for myeloablative conditioning. In this study Reduced intensity conditioning (RIC) conditioning is used and followed by match aploidentical donor peripheral blood stem cell transplantation.

Description

The objectives for the study are listed below:

Primary Objectives

-Determine the safety, and feasibility of administration of several dose combinations of conventional T-cells (Tcon) and regulatory T-cells (Treg)

Secondary Objectives

  • To determine the GVHD-free relapse-free survival (GRFS) post-HCT
  • To determine the overall survival (OS) post-HCT
  • To measure the incidence and severity of acute and chronic GVHD

Details
Condition myelodysplastic syndrome (mds), MYELODYSPLASTIC SYNDROME, chronic myelogenous leukemia, Myeloproliferative Neoplasms, Preleukemia, Advanced Hematologic Malignancies, Chronic Myeloid Leukemia, acute leukemias, Allogeneic Hematopoietic Cell Transplantation, myelodysplastic syndromes, myeloproliferative neoplasm, Chronic myeloid leukemia, Allogeneic Hematopoietic Stem Cell Transplantation, Myelodysplastic Syndromes (MDS), myeloproliferative disorders, Bone marrow disorder, Bone Marrow Disorder, MYELOPROLIFERATIVE DISORDER, Acute Leukemia
Treatment cyclophosphamide, melphalan, Fludarabine, Tacrolimus, Plerixafor, CliniMACS CD34 Reagent system, Purified regulatory T-cells (Treg) plus CD34+ HSPC, Filgrastim granulocyte colony-stimulating factor (G-CSF) or equivalent
Clinical Study IdentifierNCT05088356
SponsorStanford University
Last Modified on4 November 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Recipient Inclusion Criteria
Patients with the following diseases that are histopathologically-confirmed are eligible
Acute myeloid, lymphoid, or mixed phenotype leukemia in complete remission (CR) or CR with incomplete hematologic recovery (CRi) or beyond first complete remission (CR1) without the presence of minimal residual disease
Acute myeloid, leukemia, or mixed phenotype leukemia that is either
Not in morphologic CR with bone marrow infiltration by leukemic blasts of 10%, or
In morphologic CR with evidence of minimal residual disease positivity by either multiparametric flow cytometric analysis or by a nucleic acid-based technique
Primary refractory acute myeloid, lymphoid, or mixed phenotype leukemia
Chronic myelogenous leukemia (accelerated, blast or second chronic phase)
Myelodysplastic syndromes
Myelofibrosis that is transplant-eligible
Myeloproliferative syndromes
Blastic plasmacytoid dendritic cell neoplasm
Non-Hodgkin lymphoma with poor risk features not suitable for autologous HCT
Match to the patient as follows
For Arm A
Availability of a 8/8 or 7/8 HLA-matched donor (related or unrelated) defined by Class I (HLA-A, -B, -C) serologic typing (or higher resolution) and Class II (HLA-DRB1) molecular typing
If the donor is a 7/8 HLA-match, the mismatch must be a permissive allelic mismatch as assessed by an independent HLA and transplantation expert. b. For Arm B
Availability of a haploidentical donor who is a 4/8 but <7/8 match at HLA-A, -B, -C, and -DRB1 (typed using DNA-based high-resolution methods), with at most one mismatch per locus c. Age 18 and 75 years old at the time of enrollment. d. Left ventricular ejection fraction (LVEF) 45% e. Diffusing capacity of the lungs for carbon monoxide (DLCO) 50% f. Calculated creatinine clearance 50 mL/min or creatinine < 2.0 mg/dL
SGPT and SGOT 5 x ULN, unless elevated secondary to disease Total bilirubin 3 x ULN (patients with Gilbert's syndrome may be included at the discretion of the PI or where hemolysis has been excluded h. Negative serum or urine beta-HCG test in females of childbearing potential within 3 weeks of registration i. Karnofsky performance status 70%
Donor Inclusion Criteria
Age 18 and 75 years of age
Karnofsky performance status of 70% defined by institutional standards
Seronegative for HIV-1 RNA PCR; HIV 1 and HIV 2 ab (antibody); HTLV-1 and HTLV-2 ab; PCR+ or sAg (surface antigen) hepatitis B ; or PCR or sAg negative for hepatitis C; negative for the Treponema palladum antibody Syphillis screen; and negative for HIV-1 and hepatitis C by nucleic acid testing (NAT) within 30 days of apheresis collection
In the case that T palladum antibody tests are positive, donors must
Be evaluated and show no evidence of syphilis infection of any stage by
physical exam and history Have completed effective antibiotic therapy to treat
syphilis Have a documented negative non-treponemal test (such as RPR) or in
the case of a positive non-treponemal test must be evaluated by an infectious
disease expert to evaluate for alternative causes of test positivity and
confirm no evidence of active syphilitic disease e. Match to the patient as
follows
Arm A
Must be a related or unrelated, 8/8 or 7/8-HLA match to recipient at HLAA, -B, -C, and -DRB1. If 7/8 HLA-matched, must be with permissive allelic HLA mismatch as assessed by an independent HLA and transplantation expert. b. Arm B
Must be a haploidentical donor who is 4/8 but < 7/8 match at HLA-A, -B
C, and -DRB1, with at most one mismatch per locus. f. Must be willing to donate PBSC for up two consecutive days g. Female donors of child-bearing potential must have a negative serum or urine beta HCG test within 3 weeks of mobilization h. Capable of undergoing leukapheresis, have adequate venous access, and be willing to undergo insertion of a central catheter should leukapheresis via peripheral vein be inadequate i. Agreeable to 2nd donation of PBPC (or bone marrow harvest) in the event of graft failure j. The donor or legal guardian greater than 18 years of age, capable of signing an IRB approved consent form. k. Meets other criteria for donation as specified by standard NMDP guidelines (NMDP donors) or institutional standards (non-NMDP donors)

Exclusion Criteria

Recipient Exclusion Criteria
Seropositive for any of the following
HIV antibodies; hepatitis B surface antigen (sAg); hepatitis C antibodies
\. Prior myeloablative therapy or hematopoietic cell transplant
\. Patients deemed candidates for fully myeloablative preparative
conditioning regimens
\. Candidate for autologous transplant
\. HIV-positive
\. Active uncontrolled bacterial, viral or fungal infection, defined as
currently taking antimicrobial therapy and progression of clinical symptoms
\. Uncontrolled CNS disease involvement
\. Pregnant or a lactating female
\. Positive serum or urine beta-HCG test in females of childbearing potential
within 3 weeks of registration
\. Psychosocial circumstances that preclude the patient being able to go
through transplant or participate responsibly in follow-up care
\. Known allergy or hypersensitivity to, or intolerance of, tacrolimus
\. Hematopoietic cell transplantation-specific comorbidity index (HCT-CI) 5
\. Positive anti-donor HLA antibodies against a mismatched allele in the
selected donor determined by either
A positive crossmatch of any titer; or
The presence of anti-donor HLA antibody to any HLA locus 14. Any uncontrolled autoimmune disease requiring active immunosuppressive treatment 15. Concurrent malignancies or active disease within 1 year, except nonmelanomatous skin cancers that have been curatively resected
Donor Exclusion Criteria
Evidence of active infection
Seropositive for HIV-1 or-2, HTLV-1 or -2
Medical, physical, or psychological reason that would place the donor at increased risk for complications from growth factor or leukapheresis
Lactating female
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note