Allogeneic Hematopoietic Cell Transplantation for Peripheral T Cell Lymphoma
This study aims to evaluate the effectiveness of allogeneic hematopoietic cell transplantation in improving progression-free survival for patients with peripheral T cell lymphoma.
ATL-RIC
+ allo HCT
+ GVHD prophylaxis
Autoimmune Diseases+11
+ Hemic and Lymphatic Diseases
+ Immune System Diseases
Treatment Study
Summary
Study start date: April 18, 2019
Actual date on which the first participant was enrolled.This clinical trial is exploring a new way to treat peripheral T-cell lymphomas (PTCL), a type of blood cancer that often doesn't respond well to standard chemotherapy. The study is focused on using allogeneic hematopoietic cell transplantation (HCT), a process where patients receive blood-forming stem cells from a donor. This treatment aims to offer a potential cure for PTCL. The trial targets patients aged 12 and above, whose disease has either come back after treatment or has not responded to previous therapies. The study is important because it may help to improve survival rates and offer new hope for patients with PTCL, a condition that currently has limited treatment options. Participants in the study will receive treatment based on one of four plans, depending on their specific health needs and risk factors. Each plan involves different combinations of medications and dosages, including drugs like e-ATG, pentostatin, cyclophosphamide, and busulfan, administered through injections or orally. The trial measures the effectiveness of these treatments by looking at how many patients remain alive and free from cancer progression one year after the transplant. Safety is a priority, with adjustments made for those who may be at risk of severe side effects from certain drugs. The results of this study could guide future treatments and improve outcomes for those suffering from PTCL.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.330 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.From 12 to 120 Years
Range of ages for which participants are eligible to join.Healthy volunteers allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
* INCLUSION CRITERIA-RECIPIENT: * 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. EXCLUSION CRITERIA-RECIPIENT: * 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 INCLUSION CRITERIA-RELATED DONOR: -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. EXCLUSION CRITERIA-RELATED DONOR: None INCLUSION CRITERIA (UNRELATED DONOR): -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. EXCLUSION CRITERIA (UNRELATED DONOR): -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.
Study Plan
Find out more about all the medication administered in this study, their detailed description and what they involve.4 intervention groups are designated in this study
This study does not include a placebo group
Treatment Groups
Group I
ExperimentalGroup II
ExperimentalGroup III
ExperimentalGroup IV
ExperimentalStudy Objectives
Primary Objectives
Secondary Objectives
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 2 locations
National Institutes of Health Clinical Center
Bethesda, United StatesOpen National Institutes of Health Clinical Center in Google MapsNational Marrow Donor Program
Minneapolis, United States