💬In plain words
What the trial is, and whether it could suit you
Background:
People living with HIV(PLWH) are at a higher risk for cancers that may be curable with a bone marrow transplant. HIV infection itself is no longer a reason to not get a transplant, for patients who otherwise have a standard reason to need transplant.
Objective:
This study is being done to see if a new combination of drugs (cyclophosphamide, maraviroc, and bortezomib) is both safe and effective at protecting against graft-versus-host disease after bone marrow transplant. The study will also test the transplant s impact on your survival and control of your cancer.
Eligibility:
People aged 18 years and older living with HIV and a blood cancer that is eligible for a transplant. Healthy family members aged 12 or older who are half matched to transplant recipients are also needed to donate bone marrow.
Design:
The study will be done in 2 phases. The first phase will be to se
Sign in to get the eligibility rules as simple questions to take to your doctor.
📋 Eligibility rules (as published)
* INCLUSION CRITERIA - RECIPIENT:
* Participants must have a histologically or cytologically confirmed hematologic malignancy with standard indication for allogeneic hematopoietic cell transplantation including, but not limited to, one of the following:
* Acute myeloid leukemia in morphologic complete remission (\<5% blasts in the bone marrow, no detectable abnormal peripheral blasts, and no extramedullary disease)
* Any secondary and/or treatment related myeloid neoplasm with antecedent history of myeloid neoplasm or previous chemotherapy/radiation
* B-cell acute lymphoblastic leukemia in first or subsequent complete remission
* T-cell acute lymphoblastic leukemia in first or subsequent complete remission
* Myelodysplastic syndrome of intermediate or higher score by the Revised International Prognostic Scoring System (IPSS-R)
* Primary myelofibrosis of intermediate-2 or higher risk by the Dynamic IPSS-Plus (DIPSS-Plus) or high to very high risk score (5 or higher) calculated with MIPSS70+ Calculator; DIPSS-Plus For Myeloproliferative Neoplasms on the Mutation Enhanced International Prognostic Score System (MIPSS70/MIPSS70+)
* Chronic myelomonocytic leukemia
* Chronic myelogenous leukemia resistant to or intolerant of \>=3 tyrosine kinase inhibitors or with history of accelerated phase or blast crisis
* B-cell lymphoma including Hodgkin lymphoma that has relapsed/progressed within 1 year of completion of primary treatment, after autologous transplantation or has progressed through at least 2 lines of therapy
* Burkitt or lymphoblastic lymphoma: high-risk disease in first remission, progression/relapse after \>=1 previous regimen
* Chronic lymphocytic leukemia with 17p deletion and/or unmutated IgHv or refractory or intolerant of both BTK and PI3K inhibitors
* Mature T or NK neoplasms as defined in the WHO guidelines of sufficient type and severity for allogeneic HCT based on published clinical practice guidelines
* T-Prolymphocytic leukemia progressing/relapsing after alemtuzumab and at least one other regimen
* B-Prolymphocytic leukemia progressing/relapsing after fludarabine and at least one other salvage regimen
* Hematologic malignancy of dendritic cell or histiocytic cell type
* Multiple myeloma that relapses after therapy with both a proteasome inhibitor and an immunomodulatory drug (IMiD), relapses after autologous transplantation, or manifests as plasma cell leukemia
In addition to standard indications for HCT: Participant with a hematologic malignancy eligible for consolidation of first remission with autologous transplantation, if autologous transplantation is not accessible to the participant.
* HIV seropositive, with ART regimen that, when stable for \>4 weeks, is associated with an HIV viral load \<400 copies/mL at screening evaluations. Subsequent changes to avoid/optimize drug interactions with study drugs or essential supportive care drugs may be made to the ART regimen at any time during the eligibility assessment period, as long as the eligibility criteria were met and the regimen change is expected, by the study team and involved consultants/pharmacy, to be similarly effective for HIV control. These changes to the ART regimen are not part of the study. If changes to the ART regimen are made during the eligibility period, HIV viral load will be rechecked at least 1 week after the change but prior to protocol treatment consent.
* Dose level 1: ART regimen must include maraviroc
* Dose level 2 and 3: ART regimen must not include maraviroc and there must be no history of maraviroc intolerance or resistance
* Age \>= 18 years
* At least one potentially suitable HLA-haploidentical first degree or collateral related donor. Recipients with donor-specific anti-HLA antibodies (DSAs) to all potential donors must have at least one potential donor option where the DSA strength has a mean fluorescence intensity of \< 5000 and antibodies are not complement-fixing.
* Karnofsky performance score \>=50 percent.
* Adequate organ function defined as possessing all of the following:
* Cardiac ejection fraction by 2D ECHO of \>=40 percent
* Forced expiratory volume-1 (FEV-1), forced vital capacity (FVC), and diffusing capacity of the lung for carbon monoxide (DLco, adjusted for hemoglobin) all of \>=40 percent predicted. 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 percent on room air.
* Total bilirubin \<=3.0 mg/dL (unless due to Gilbert's or hemolysis), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) \<= 5x the upper limit of normal, gamma glutamyl transferase (GGT) \<= 5x the upper limit of normal
* Estimated serum creatinine clearance of \>=50 mL/min/1.73m2 calculated using eGFR in the clinical lab
* Ability of participant to understand and the willingness to sign a written informed consent document.
* Individuals of childbearing potential and those that 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:
* Participants who are receiving any other investigational agents that cannot be discontinued/completed at least 2 weeks prior to the date of beginning conditioning.
* Poorly controlled malignant indication for transplantation, defined as:
* Leukemia not having achieved morphologic remission (i.e. bone marrow blasts \>5 percent or active extramedullary disease)
* Lymphoma not having demonstrated some degree of treatment sensitivity (chemosensitivity, radiosensitivity) by clinical and/or radiologic assessment
* Multiple myeloma not in complete remission, as determined by negative immunofixation in serum and urine and disappearance of any soft tissue plasmacytomas and \<= 5 percent plasma cells in the bone marrow.
* Uncontrolled intercurre
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