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New treatment option for Recurrent Severe Aplastic Anemia
Official title A Reduced-Intensity Conditioning Regimen (Cyclophosphamide, Pentostatin, Anti-thymocyte Globulin) Followed by Haploidentical Hematopoietic Stem Cell Transplant for the Treatment of Patients With Refractory or Recurrent Severe Aplastic Anemia
ClinicalTrials.gov ID: NCT05757310
What this study is testing
What is Anti-Thymocyte Globulin?
Anti-Thymocyte Globulin is an investigational medicine, given as an infusion into a vein, being studied as a potential treatment for recurrent severe aplastic anemia.
Also referred to as Antithymocyte Globulin, Antithymocyte Serum.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- This phase I trial evaluates the safety and feasibility of using a reduced-intensity regimen of cyclophosphamide, pentostatin, and anti-thymocyte globulin prior to a CD4+ T-cell depleted haploidentical hematopoietic cell transplant (haploHCT) for the treatment of patients with severe aplastic anemia that does not respond to treatment (refractory) or that has come back (recurrent). Cyclophosphamide is in a class of medications called alkylating agents.
- Phase 1: an early, usually small safety study
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages up to 75. Healthy volunteers may be eligible.
You may be able to join if
- RECIPIENT: Documented informed consent of the participant.
- RECIPIENT: Age: \>= 40 years but =\< 75 years of age at time of enrollment.
- RECIPIENT: Failed at least one trial of immunosuppressive therapy (IST) by being refractory (persistence of severe cytopenia and fulfillment of SAA...
- RECIPIENT: Karnofsky performance score \>= 60%.
- RECIPIENT: Confirmed diagnosis of severe aplastic anemia as:
You likely can't join if
- RECIPIENT: Inherited and acquired (non-aplastic anemia) bone marrow failure syndromes such as Fanconi anemia must be ruled out according to center...
- RECIPIENT: Clonal cytogenetic abnormalities consistent with pre-myelodysplastic syndrome (pre-MDS) or MDS on marrow examination (e.g. Monosomy 7).
- RECIPIENT: Any somatic mutations (including TERT, TERC, DKC1, NOP10) other than PIG-A (PNH) or BCOR mutation.
- RECIPIENT: Diagnosis of myelodysplastic syndrome (MDS).
- RECIPIENT: Presence of anti-donor HLA antibodies (positive anti-donor HLA antibody is defined as a positive cross-match test of any titer by...
- RECIPIENT: Prior allogeneic stem cell transplant.
See the full eligibility criteria
Who can join
- RECIPIENT: Documented informed consent of the participant.
- RECIPIENT: Age: \>= 40 years but =\< 75 years of age at time of enrollment.
- RECIPIENT: Failed at least one trial of immunosuppressive therapy (IST) by being refractory (persistence of severe cytopenia and fulfillment of SAA disease criteria at least 3 months after initial IST) or having...
- RECIPIENT: Karnofsky performance score \>= 60%.
- RECIPIENT: Confirmed diagnosis of severe aplastic anemia as:
- Bone marrow cellularity \< 25% or marrow cellularity \< 50% but with \< 30% residual hematopoietic cells;
- Two out of three of the following (in peripheral blood):
- Neutrophils \< 0.5 x 10\^9/L;
- Platelets \< 20 x 10\^9/L;
- Reticulocyte count \< 20 x 10\^9/L (\< 60 x 10\^9/L using an automated analysis).
- RECIPIENT: No suitable fully matched related sibling donor (6/6 match for human leukocyte antigen [HLA]-A and B at intermediate or high resolution and DRbetaA1 at high resolution using deoxyribonucleic acid [DNA]-based...
- RECIPIENT: Available relative of the patient who is a haploidentical match, including biological parents, siblings or half siblings, children, uncles/aunts, first cousins, etc. Eligible haploidentical donors will have...
- RECIPIENT: Patient and/or legal guardian must sign informed consent for the hematopoietic stem cell transplantation (HSCT).
- RECIPIENT: The haplo donor and/or legal guardian must be able to sign informed consent documents.
- RECIPIENT: The potential haplo donor must be willing and able to donate bone marrow.
- RECIPIENT: The weight of the haplo donor must be \>= 20 kg.
- RECIPIENT: Total bilirubin \< 3.0 x the upper limit of normal (ULN) for age (patients who have been diagnosed with Gilbert's Disease are allowed to exceed this limit)
- RECIPIENT: Aspartate aminotransferase (AST) =\< 5.0 x ULN.
- RECIPIENT: Alanine transaminase (ALT) =\< 5.0 x ULN.
- RECIPIENT:
- For patients \>= 13.0 years of age at the time of enrollment: Creatinine clearance of \>= 50 mL/min per 24 hour urine test or the Cockcroft-Gault formula.
- For patients \ 90 mL/min/1.73 m\^2. If the estimated GFR is \ 50mL/min/1.73m\^2.
- RECIPIENT: Women of childbearing potential (WOCBP): negative urine or serum pregnancy test If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- RECIPIENT: Echocardiogram (ECHO) or multigated acquisition (MUGA): Left ventricular ejection fraction (LVEF) at rest \>= 40%. For patients aged \ = 26% by echocardiogram or MUGA may be substituted for LVEF.
- RECIPIENT:
- For patients \> 13.0 years of age: Diffusing capacity of the lung for carbon monoxide (DLCO) (corrected/adjusted for hemoglobin) \> 40% and forced expiratory volume in 1 second (FEV1) \> 50% predicted (without...
- For patients \ 92% on room air at sea level (with lower levels allowed at higher elevations per established center standard of care [e.g., Utah, 4,200 feet above sea level, does not give supplemental oxygen unless below...
- RECIPIENT: Seronegative for human immunodeficiency virus (HIV) antigen and antibody (Ag/Ab) combo, hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative), and syphilis (rapid plasma reagin...
- If positive, hepatitis C ribonucleic acid (RNA) quantitation must be performed.
- RECIPIENT: Antibodies to donor red blood cell antigens including ABO and rhesus (Rh) meets institutional titer requirements.
- RECIPIENT: WOCBP or sexually active male: Agreement to use adequate contraception prior to study entry and 6 months post-CD4+ T-cell-depleted-HaploHCT.
- DONOR: Documented protocol-specific City of Hope (COH) informed consent per local, state and federal guidelines
- DONOR: Documented general institutional informed consent per local, state and federal guidelines.
- DONOR: Age: younger than 60 years.
- DONOR: Haplo donor selection is based on HLA typing and relationship to recipient.
- DONOR: When more than one donor is available, the donor with the lowest number of HLA allele mismatches will be chosen unless there is HLA cross-match incompatibility or a medical reason to select otherwise. In cases...
- DONOR: If there is more than one donor with the least amount of host-versus-graft (HVG) allele mismatches, the suggested prioritization in order of importance includes ABO compatibility, cytomegalovirus (CMV) status...
- DONOR: Infectious disease screening performed within 30 days prior to stem cell collection and per federal guidelines and is:
- Seronegative for HIV Ag, HIV 1+2 Ab, human T-lymphotropic virus (HTLV) I/II Ab, hepatitis B virus surface antigen (HBsAg), hepatitis B virus core antibody (HBcAb) (immunoglobulin M [IgM] and immunoglobulin G [IgG]), HCV...
- Negative RPR for syphilis.
- DONOR: WOCBP: Urine pregnancy testing performed within 7 days prior to stem cell mobilization
- DONOR: Is approved and completed evaluation per institutional guidelines.
What rules you out
- RECIPIENT: Inherited and acquired (non-aplastic anemia) bone marrow failure syndromes such as Fanconi anemia must be ruled out according to center standards.
- RECIPIENT: Clonal cytogenetic abnormalities consistent with pre-myelodysplastic syndrome (pre-MDS) or MDS on marrow examination (e.g. Monosomy 7).
- RECIPIENT: Any somatic mutations (including TERT, TERC, DKC1, NOP10) other than PIG-A (PNH) or BCOR mutation.
- RECIPIENT: Diagnosis of myelodysplastic syndrome (MDS).
- RECIPIENT: Presence of anti-donor HLA antibodies (positive anti-donor HLA antibody is defined as a positive cross-match test of any titer by complement-dependent cytotoxicity or flow cytometric testing or the presence...
- RECIPIENT: Prior allogeneic stem cell transplant.
- RECIPIENT: Prior solid organ transplant.
- RECIPIENT: Known life-threatening reaction (i.e., anaphylaxis) to Thymoglobulin (registered trademark) that would prohibit use for the patient as this study requires use of the Thymoglobulin (registered trademark)...
- RECIPIENT: Uncontrolled bacterial, viral, or fungal infection at the time of enrollment. Uncontrolled is defined as currently taking medication and with progression or no clinical improvement on adequate medical...
- RECIPIENT: Seropositive for the human immunodeficiency virus (HIV).
- RECIPIENT: Active hepatitis B or C determined by a detectable viral load of HBV or HCV.
- RECIPIENT: Female patients who are pregnant (per institutional practice) or breast-feeding.
- RECIPIENT: Prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ. Cancer treated with curative intent \> 5 years previously will be allowed. Cancer treated with curative intent...
- RECIPIENT: Alemtuzumab or ATG within 2 weeks of enrollment.
- RECIPIENT: Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures.
- RECIPIENT: Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics).
- DONOR: Has undergone any transplantation (i.e. organ, stem cell, bone marrow, blood).
- DONOR: Receiving any investigational agents, or concurrent biological, chemotherapy, immunosuppression or radiation therapy.
- DONOR: Active infection.
- DONOR: Medical or physical reason which makes the donor unlikely to tolerate or cooperate with growth factor therapy and leukapheresis.
- DONOR: Factors which place the donor at increased risk for complications from leukapheresis or granulocyte colony-stimulating factor (G-CSF) therapy.
- DONOR: WOCBP: pregnant or =\< 6 months breastfeeding.
The study team makes the final eligibility decision.
Where it's taking place
- Duarte, California, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, up to 75 years. Healthy volunteers may be eligible. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Duarte, California, United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.