Allogeneic Hematopoietic Cell Transplantation for Peripheral T Cell Lymphoma
Phase II Trial of Allogeneic Hematopoietic Cell Transplantation for Peripheral T Cell Lymphoma
2 other identifiers
interventional
330
1 country
2
Brief Summary
Background: Lymphoma is a type of blood cancer. Blood cell transplant can cure some people with lymphoma. Researchers want to see if they can limit the complications transplant can cause. Objective: To test if a stem cell transplant can cure or control lymphoma. Also to test if new ways of getting a recipient ready for a transplant may result in fewer problems and side effects. Eligibility: Recipients: People ages 12 and older with peripheral T cell lymphoma that does not respond to standard treatments Donors: Healthy people ages 18 and older whose relative has lymphoma Design: Participants will be screened with: Physical exam Blood and urine tests Bone marrow biopsy: A needle inserted into the participant s hip bone will remove marrow. Donors will also be screened with: X-rays Recipients will also be screened with: Lying in scanners that take pictures of the body Tumor sample Donors may donate blood. They will take daily shots for 5 7 days. They will have apheresis: A machine will take blood from one arm and take out their stem cells. The blood will be returned into the other arm. Recipients will be hospitalized at least 2 weeks before transplant. They will get a catheter: A plastic tube will be inserted into a vein in the neck or upper chest. They will get antibody therapy or chemotherapy. Recipients will get the transplant through their catheter. Recipients will stay in the hospital several weeks after transplant. They will get blood transfusions. They will take drugs including chemotherapy for about 2 months. Recipients will have visits 6, 12, 18, 24 months after transplant, then once a year for 5 years.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Apr 2019
Longer than P75 for phase_2
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
April 18, 2019
CompletedFirst Submitted
Initial submission to the registry
April 19, 2019
CompletedFirst Posted
Study publicly available on registry
April 22, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 31, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
October 31, 2030
April 28, 2026
April 24, 2026
7.5 years
April 19, 2019
April 25, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Progression-free survival (PFS) of HCT recipients on the RIC arm and the mRIC arm
Number of patients who are alive and with PFS at one year, assessed by Kaplan-Meier with 80% and 95% two-sided confidence intervals
1 year post transplant
Progression-free survival (PFS) of HCT recipients on the IOC arm and ATL-RIC arm
Number of patients who are alive and with PFS at one year, assessed by Kaplan-Meier with 80% and 95% two-sided confidence intervals
1 year post transplant
Secondary Outcomes (14)
Incidence of Acute Graft versus-host disease
1 year post transplant
Incidence of Chronic Graft versus-host disease
1 and 2 years post transplant
primary graft failure
60 days post transplant
secondary graft failure
1 year post transplant
lymphoma relapse
1, 3, and 5 years post transplant
- +9 more secondary outcomes
Study Arms (5)
1/RIC Arm
EXPERIMENTALReduced Intensity Conditioning Arm, plus allogeneic HCT with GVHD prophylaxis
2/IOC Arm
EXPERIMENTALImmunosuppression Only Conditioning, plus allogeneic HCT with GVHD prophylaxis
3/Donor Arm
NO INTERVENTIONDonors for Recipients in Arm 1, Arm 2, Arm 4, or Arm 5
4/mRIC Arm
EXPERIMENTALmodified Reduced Intensity Conditioning Arm, plus allogeneic HCT with GVHD prophylaxis
5/ATL-RIC Arm
EXPERIMENTALmodified Reduced Intensity Conditioning Arm for ATL patients, plus allogeneic HCT with GVHD prophylaxis
Interventions
e-ATG 40 mg/kg/day IV on days -14 and -13, pentostatin 4 mg/m2/day IV on days -11 and -7, low-dose cyclophosphamide (5 mg/kg) orally daily on days -11 through -4; busulfan IV, pharmacokinetically dosed, on days -3 and -2, filgrastim or biosimilar drug 5mcg /kg/day subcutaneous on days -12, -8, and -4, ruxolitinib 45 mg/day from day -12 through day -2, and zidovudine 300mg orally three times a day from day -1 through day +50.
e-ATG 40 mg/kg/day IV on days -14 and -13, pentostatin 4 mg/m2/day IV on days -11 and -7, lowdose cyclophosphamide (5 mg/kg) orally daily on days -11 through -4; busulfan IV, pharmacokinetically dosed, on days -3 and -2, filgrastim or biosimilar drug 5 mcg/kg/day subcutaneous on days -12, -8, and -4.
e-ATG 40 mg/kg/day IV on days -14 and -13. Pentostatin 4mg /m2/day IV on days -11 and -7. Cyclophosphamide 5 mg/kg orally daily on days -11 through -4. Busulfan IV, pharmacokinetically dosed, on days -3 and -2.
High-dose, post-transplantation cyclophosphamide (PTCy) on days +3 and +4 ( 25 mg/kg/day on both arms), sirolimus on days +5 through +60, and mycophenolate mofetil (MMF) on days +5 through +25.
e-ATG40 mg/kg/day IV on days -14 and -13. Pentostatin 4 mg/m2/day IV on days -9 and -5. Cyclophosphamide 5 mg/kg orally daily on days -9 through -2
Eligibility Criteria
You may qualify if:
- Age \>=12 years
- Diagnosis of PTCL, confirmed by NCI pathology review, that is relapsed or refractory to prior therapy, and/or PTCL where upfront allo HCT in first remission is reasonable (PIT score of intermediate-low risk or higher or supported by clinical practice guidelines)
- ALK-positive ALCL patients will only be eligible if relapsed or refractory
- At least one potential 7-8/8 HLA-matched related (excluding an identical twin) or unrelated donor (at HLA-A, -B, -C, and DR), or an HLA-haploidentical related donor, based on initial low resolution unrelated donor search and/or at least one biologically-related family member who has at least a 25% chance of being at minimum an HLAhaploidentical match and is potentially suitable to donate based on reported family history. HLA typing of potential donors and/or mutation testing does not need to be completed for eligibility.
- Adequate end-organ function, as measured by:
- For RIC: Left ventricular ejection fraction (LVEF) \>= 40% by 2D echocardiogram (ECHO) or MUGA, left ventricular shortening fraction \>= 20% by ECHO, or LVEF \>= 30% if the patient has radiologic evidence of aortic, renal, or coronary artery vasculitis. For IOC: LVEF \>= 30% by 2D ECHO or MUGA.
- Pulmonary function tests: DLco (corrected for hemoglobin) and FEV1 \>= 40% of predicted for the RIC arm, and \>= 30% predicted for the IOC arm; or in pediatric patients, if unable to perform pulmonary function tests, there should be no evidence of dyspnea at rest, no requirement for supplemental oxygen, and oxygen saturation \>92% on room air.
- Bilirubin \<= 3.0 mg/dL (unless due to Gilbert's syndrome or hemolysis) for patients receiving RIC and bilirubin \<= 5.0 mg/dL for patients receiving IOC (unless due to Gilbert s syndrome or hemolysis); ALT and AST \<= 10 x ULN for patients receiving RIC or IOC. Patients who are above these bilirubin, ALT, or AST thresholds may be eligible for the RIC or IOC arm if evaluated by a hepatologist who deems the liver function test abnormalities to be potentially disease related, either because of direct involvement by PTCL, due to an associated process such as hemophagocytic lymphohistiocytosis, or as sequelae of prior chemotherapy that is thought to improve with time.
- Estimated creatinine clearance of \>= 50 mL/min/1.73 m\^2, calculated using eGFR in the clinical lab for adults and the Schwartz formula for pediatrics.
- Karnofsky (adults) or Lansky (children) performance status of \>= 50% or ECOG performance status of 2 or less for the RIC arm and Karnofsky (adults) or Lansky (children) \>= 30% or ECOG performance status of 3 or less for the IOC arm
- Ability of subject or parent/guardian to understand and the willingness to sign a written informed consent document
- Not pregnant or breastfeeding.
- As therapeutic agents used in this trial may be harmful to a fetus, individuals of childbearing potential and individuals who can father children must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for at least one year post-allo HCT.
You may not qualify if:
- Patients who are receiving any other investigational agents, with the exception of virus-specific cytotoxic T-cells for the treatment of viral infection/reactivation prior to allo HCT.
- Prohibitive allergy to a study drug or to compounds of similar chemical or biologic composition of the agents (e-ATG, steroids, cyclophosphamide, busulfan, pentostatin, sirolimus, MMF, filgrastim or biosimilar drug) used in the study
- Lack of central venous access potential
- Active psychiatric disorder which is deemed by the PI to have significant risk of compromising compliance with the transplant protocol or which does not allow for appropriate informed consent
- Related donor deemed suitable and eligible, and willing to donate, per clinical evaluations who are additionally willing to donate blood and/or peripheral blood stem cells for research. Related donors will be evaluated in accordance with existing Standard Policies and Procedures for determination of eligibility and suitability for clinical donation.
- None
- Unrelated donors will be evaluated in accordance with existing NMDP Standard Policies and Procedures, available at: http://bethematch.org/About-Us/Global-transplantnetwork/ Standards/, except for the additional requirement of EBV serostatus testing for clinical purposes of donor selection. Note that participation in this study is offered to all unrelated donors but not required for clinical donation, so it is possible that not all unrelated donors will enroll on this study. Unrelated donors only enroll if they contribute research specimens, which is optional.
- Unrelated donors: failure to qualify as a National Marrow Donor Program (NMDP) donor per current NMDP Standards, available at: http://bethematch.org/About-Us/Globaltransplant- network/Standards/. Exceptions to donor eligibility (e.g. foreign travel, tattoos) do not automatically exclude the donor and will be reviewed by the PI.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
National Marrow Donor Program
Minneapolis, Minnesota, 55401, United States
Related Links
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Dimana Dimitrova, M.D.
National Cancer Institute (NCI)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 19, 2019
First Posted
April 22, 2019
Study Start
April 18, 2019
Primary Completion (Estimated)
October 31, 2026
Study Completion (Estimated)
October 31, 2030
Last Updated
April 28, 2026
Record last verified: 2026-04-24
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as the database is active.
- Access Criteria
- Clinical data will be made available via subscription to BTRIS and with permission of the study PI. Genomic data are made available via dbGAP through requests to the data custodians
All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing data will be shared with subscribers to dbGAP.