High Dose Vitamin A for Stem Cell Transplant Recipients
Recruiting in Palo Alto (17 mi)
Overseen byHannah Choe, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Ohio State University Comprehensive Cancer Center
Disqualifiers: Vitamin A allergy, Abnormal liver enzymes, Pregnancy, others
No Placebo Group
Trial Summary
What is the purpose of this trial?This phase I trial studies the side effects and how well high dose vitamin A works in preventing gastrointestinal graft versus host disease (GVHD) in participants undergoing donor stem cell transplant. Vitamin A deficiency is associated with increased risk of gastrointestinal GVHD. Vitamin A regulates growth and differentiation of intestinal cells and may reduce risk of gastrointestinal GVHD.
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop taking your current medications. However, if you have a history of allergic reactions to Vitamin A or similar issues, it might affect your participation.
What data supports the effectiveness of the drug Vitamin A Compound for stem cell transplant recipients?
Research shows that Vitamin A, particularly its derivatives called retinoids, can enhance immune functions and may help in cancer treatment by affecting cell growth and survival. This suggests potential benefits for stem cell transplant recipients, as these processes are crucial for recovery and engraftment.
12345Is high dose Vitamin A generally safe for humans?
High doses of Vitamin A can cause several side effects, including changes in mood and behavior, liver enlargement, increased blood fat levels, and skin dryness. In infants, excessive Vitamin A can lead to severe anemia and low platelet counts. Most side effects are reversible, but liver and bone issues may persist.
26789How does the drug Vitamin A Compound differ from other treatments for stem cell transplant recipients?
The use of high-dose Vitamin A, specifically all-trans retinoic acid, is unique because it enhances the maintenance and self-renewal of stem cells, which may improve the success of stem cell transplants. This approach is different from standard treatments as it focuses on promoting the engraftment and long-term repopulating activity of stem cells.
36101112Eligibility Criteria
This trial is for adults set to have a stem cell transplant from a donor who matches their human leukocyte antigen (HLA) or is slightly mismatched. They should be undergoing this procedure due to blood cancers and can have either intense or less intense pre-transplant treatments.Inclusion Criteria
Adult patients planned to undergo an allogeneic stem cell transplant (SCT) with an human leukocyte antigen (HLA)-matched (unrelated or related) or 1 allele mismatched (7/8) donor or haploidentical donor who received either myeloablative or nonmyeloablative conditioning for hematologic malignancies are eligible
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive a single, high dose of vitamin A orally or enterally prior to stem cell transplant. A second dose may be administered two weeks after transplant if vitamin A levels have not improved.
2 weeks
1 visit (in-person) for initial dose, potential follow-up for second dose
Follow-up
Participants are monitored for safety, effectiveness, and incidence of gastrointestinal GVHD after treatment. Stool samples are collected for microbiome analysis.
28 days
Periodic follow-up visits
Long-term follow-up
Participants are monitored for the incidence of gastrointestinal GVHD up to 180 days after stem cell transplant.
180 days
Participant Groups
The study tests if high doses of vitamin A can prevent gastrointestinal problems after receiving a stem cell transplant from a donor. It's in the early stages, focusing on safety and how well it works to stop these complications.
2Treatment groups
Experimental Treatment
Active Control
Group I: Treatment Cohort (vitamin A compound)Experimental Treatment1 Intervention
Participants receive vitamin A compound PO or enterally once prior to stem cell transplant.
once over a given 24 hour period with or without food. We will re-dose at 2000 IU/kg (maximum 120,000 IU) if Week 2 Vitamin A levels remain within 10% of baseline Vitamin A.
Group II: Control Cohort (usual care)Active Control1 Intervention
Patients receive usual care.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Ohio State University Comprehensive Cancer CenterColumbus, OH
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Who Is Running the Clinical Trial?
Ohio State University Comprehensive Cancer CenterLead Sponsor
References
[Vitamin A augmentation of the effects of chemotherapy in metastatic breast cancers after menopause. Randomized trial in 100 patients]. [2007]Vitamin A was administered to randomly allocated patients in a group of 100 patients with metastatic breast carcinoma treated by chemotherapy. The daily doses (given indefinitely) ranged from 350,000 to 500,000 IU according to body weight. A significant increase in the complete response rate was observed. When subgroups determined by menopausal status were considered, it was observed that serum retinol levels were only significantly increased in the post-menopausal group on high dose Vitamin A. Response rates, duration of response and projected survival were only significantly increased in this subgroup. The therapeutic and biological implications of these findings are discussed.
Pharmacokinetics of intravenously administered liposomal all-trans-retinoic acid (ATRA) and orally administered ATRA in healthy volunteers. [2022]To determine single-and multiple-dose pharmacokinetics of liposomal-all- trans -retinoic acid (Atragen) following intravenous and oral ATRA (Vesanoid) administration in healthy volunteers.
[Experimental study on promoting the engraftment of hematopoietic stem/progenitor cell by all-trans retinoic acid]. [2013]To explore the effect of all-trans retinoic acid (RA) on the engraftment of unrelated umbilical cord blood stem/progenitor cell transplantation (UCBT) in murine model.
Randomized trial of vitamin A versus observation as adjuvant therapy in high-risk primary malignant melanoma: a Southwest Oncology Group study. [2017]A national cooperative group trial was conducted in patients with early-stage cutaneous malignant melanoma to determine if oral vitamin A can increase disease-free survival or survival.
Retinoids as critical modulators of immune functions: new therapeutic perspectives for old compounds. [2021]Retinoids are vitamin A derivatives that critically regulate several physiological and pathological processes, including immune functions and cancer development. These biological response modifiers exert their pleiotropic effects through the interaction with nuclear receptors, defined as retinoic acid receptors (RARs) and retinoid X receptors (RXRs). These ligand-activated nuclear receptors induce the transcription of target genes by binding to responsive elements in the promoter regions. RARs and RXRs are also capable to interact with other nuclear receptors, thus expanding their spectrum of action on gene expression. Evidence has been accumulated indicating that retinoids may exert beneficial effects in both immune-mediated disorders and tumors. With regard to cancer, retinoids directly target neoplastic cells by inducing differentiation, inhibiting cell growth or promoting survival. However, the efficacy of these compounds in cancer treatment probably resides in their ability to modulate also the function of immune effectors. Vitamin A derivatives are currently used in the therapy of acute promyelocytic leukemia and of cutaneous T cell lymphomas, but they could be effective also on B-cell malignancies. Clinical trials are ongoing to test their efficacy in solid tumors. In this review, we give a broad depiction of how retinoids influence the function of immune effectors and affect growth and survival of hematological malignancies. This with the aim to better understand the clinical effects of retinoid-based therapies and provide the rationale to combine retinoids with other active compounds in new synergistic treatment strategies.
Phase I trial of retinol in cancer patients. [2017]Vitamin A (all-trans-retinol) and its analogues are undergoing evaluation as antineoplastic and chemoprevention agents. Because its toxicity and activity are poorly defined, we have completed a phase I trial of retinol. Retinol was administered to 13 cancer patients in daily doses ranging from 100,000 units/m2 to 350,000 units/m2. Neuropsychiatric changes were the earliest dose-limiting symptomatic toxicities, noted in 3 of 5 patients receiving more than 240,000 U/m2 for 3-4 months. Two patients receiving more than 270,000 U/m2 developed hepatomegaly after 3 and 4 months. Liver biopsies were consistent with vitamin A toxicity. Three patients receiving 200,000 U/m2 developed an increase in serum triglycerides concentration. Mild skin and mucous membrane dryness occurred in most patients receiving more than 150,000 U/m2. A mixed response was seen in one patient with melanoma. Because of neuropsychiatric and hepatic toxicity a retinol dose of 200,000 U/m2/day is recommended for future phase II trials.
Infant hypervitaminosis A causes severe anemia and thrombocytopenia: evidence of a retinol-dependent bone marrow cell growth inhibition. [2021]Vitamin A is a pivotal biochemical factor required for normal proliferation and differentiation as well as for specialized functions, such as vision. The dietary intake of 1500 IU/day is recommended in the first year of life. Here, we report the case of an infant who had been given 62 000 IU/day for 80 days. The infant showed several clinical signs of retinol intoxication, including severe anemia and thrombocytopenia. Bone marrow showed a remarkably reduced number of erythroid and megakaryocytic cells. The interruption of vitamin A treatment was immediately followed by clinical and biochemical recovery. To clarify whether the effects of retinol are due to a direct action on bone marrow cell proliferation, we investigated the activity of retinol (both the drug and the pure molecule) on the growth of K-562, a multipotent hematopoietic cell line, and on bone marrow mesenchymal stem cells. We observed that vitamin A strongly inhibited the proliferation of the cells at concentrations similar to those reached in vivo. Subsequent biochemical analyses of the cell cycle suggested that the effect was mediated by the up-regulation of cyclin-dependent kinase inhibitors, p21(Cip1) and p27(Kip1). These are the first findings to demonstrate that infant hypervitaminosis A causes a severe anemia and thrombocytopenia and that this is probably due to the direct effect of the molecule on the growth of all bone marrow cellular components. Our data also suggest potential bone marrow functional alterations after excessive vitamin A intake because of emerging social habits.
Side effects of systemic retinoids and their clinical management. [2019]The safety profile of oral retinoids appears to be well established, although rare new side effects are occasionally reported. Appropriate patient selection, use of the lowest required dose, and adequate follow-up are significant factors in the prevention of these toxicities. Teratogenicity, which can be avoided by following recommended precautions, is the main adverse effect.
Side effects and long-term toxicity of synthetic retinoids. [2016]The observation that vitamin A (retinol) has antikeratinizing properties has led to the development of synthetic retinol derivatives (retinoids) for the treatment of a variety of skin disorders characterized by abnormal keratinization. The goal of research in this area is the synthesis of retinoids that would have a more favorable therapeutic: toxic ratio than retinol itself. A limiting factor in the use of any vitamin A analogue is that, even with a more favorable therapeutic: toxic ratio, large pharmacologic doses are required that produce side effects related to the drug's action in most individuals. With few exceptions, all of the side effects are those seen from mega-vitamin A ingestion, primarily affecting the mucocutaneous, skeletal, and central nervous systems. Most of the side effects from excess vitamin A are reversible, with notable exceptions being those involving hepatic and osseous tissues. In terms of reversibility from synthetic retinoids, the experience to date has been incomplete, so there remains imprecise information as to the incidence and the persistence of toxic effects after drug withdrawal.
The effect of addition of calcipotriol ointment (50 micrograms/g) to acitretin therapy in psoriasis. [2019]Our purpose was to find out whether the addition of calcipotriol ointment (50 micrograms/g) to systemic treatment with acitretin produces additional therapeutic effects and thereby an acitretin-sparing effect, and further to investigate the safety and tolerability of this combination. A multicentre, randomized, double-blind placebo-controlled study was designed. Patients were randomized to receive calcipotriol or placebo. All patients were treated with a starting dose of 20 mg acitretin per day and doses were adjusted at 2-weekly intervals with increments of 10 mg per day up to a maximum of 70 mg per day. The dose requirement for acitretin, clinical signs and adverse events were recorded. Seventy-six patients were randomized to treatment with calcipotriol 50 micrograms/g ointment twice daily and 59 patients to treatment with the vehicle only twice daily. Clearance or marked improvement was achieved by 67% of the patients in the calcipotriol group and by 41% of the patients in the placebo group (P = 0.006). Calcipotriol treatment proved to have a statistically significant additional effect to acitretin on the Psoriasis Area and Severity Index, redness, thickness and scaliness as compared with placebo. Clearance or marked improvement was achieved with a statistically significantly lower cumulative dose of acitretin by the patients in the calcipotriol group as compared with the placebo group. The number of patients reporting adverse events was pronounced and largely related to acitretin. No significant differences were observed between the two treatment groups with respect to adverse events. Laboratory assessments were essentially normal. The addition of calcipotriol ointment to acitretin treatment contributes to the efficacy, reduces the cumulative dose of acitretin to reach marked improvement or clearance, and is well-tolerated and safe.
[Effects of retinol on expressions of epidermal growth factor, stem cell factor, colony-stimulating factor 1 and leukemia inhibitory factor in human umbilical cord-derived mesenchymal stem cells]. [2020]To investigate effects of retinol on the expressions of epidermal growth factor (EGF), stem cell factor (SCF), colony-stimulating factor 1 (CSF1) and leukemia inhibitory factor (LIF) in cultured human umbilical-derived mesenchymal stem cells (UCMSCs).
All-trans retinoic acid enhances the long-term repopulating activity of cultured hematopoietic stem cells. [2021]The retinoic acid receptor (RAR) agonist, all-trans retinoic acid (ATRA), is a potent inducer of terminal differentiation of malignant promyelocytes, but its effects on more primitive hematopoietic progenitors and stem cells are less clear. We previously reported that pharmacologic levels (1 micromol) of ATRA enhanced the generation of colony-forming cell (CFC) and colony-forming unit-spleen (CFU-S) in liquid suspension cultures of lin- c-kit+ Sca-1+ murine hematopoietic precursors. In this study, we further investigated the effects of ATRA as well as an RAR antagonist, AGN 193109, on the generation of transplantable cells, including pre-CFU-S, short-term repopulating stem cells (STRCs), and long-term repopulating stem cells (LTRCs). ATRA enhanced the ex vivo maintenance and production of competitive repopulating STRCs and LTRCs from lin- c-kit+ Sca-1+ cells cultured in liquid suspension for 14 days. In addition, ATRA prevented the differentiation of these primitive stem cells into more mature pre-CFU-S during the 14 days of culture. In marked contrast, lin- c-kit+ Sca-1+ cells cultured with AGN 193109 for 7 days had virtually no short- or long-term repopulating ability, but displayed an approximately 6-fold increase in the pre-CFU-S population. The data suggest that the RAR agonist ATRA enhances the maintenance and self-renewal of short- and long-term repopulating stem cells. In contrast, the RAR antagonist AGN 193109 abrogates reconstituting ability, most likely by promoting the differentiation of the primitive stem cells. These results imply an important and unexpected role of retinoids in regulating hematopoietic stem cell differentiation. (Blood. 2000;95:470-477)