Clinical Trials Logo

Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT01747499
Other study ID # 201303012
Secondary ID 1P50CA171963-01A
Status Terminated
Phase Phase 1/Phase 2
First received
Last updated
Start date April 15, 2013
Est. completion date December 24, 2018

Study information

Verified date September 2019
Source Washington University School of Medicine
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The purpose of this phase I/II study is to define the maximum tolerated dose of 5-AzaC and the effect on grade II-IV GvHD when given after matched unrelated donor transplant (MUD).


Recruitment information / eligibility

Status Terminated
Enrollment 54
Est. completion date December 24, 2018
Est. primary completion date August 31, 2018
Accepts healthy volunteers No
Gender All
Age group 18 Years to 70 Years
Eligibility Inclusion Criteria:

Patients must meet the following criteria within 30 days prior to Day 0 unless otherwise noted.

- Phase I: Diagnosis of any hematological malignancy listed below (excluding myelofibrosis) in remission or with stable minimal residual disease

- Acute myelogenous leukemia (AML) in 1st or subsequent remission or in relapse after any remission

- Acute lymphoblastic leukemia (ALL) in 1st or subsequent remission or in relapse after any remission

- Myelodysplastic syndrome either intermediate 1 or 2, or high risk by the International Prognostic Scoring System

- Chronic myelogenous leukemia (CML) in accelerated or second chronic phase

- Non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) in 2nd or greater complete remission, partial remission, or refractory relapse

- Chronic lymphocytic leukemia (CLL), Rai Stage 2-4, failing at least 2 prior regimens

- Multiple myeloma (MM), Stage 2-3

- Myeloproliferative disorder or neoplasm

- Phase II: Diagnosis of AML in remission 1 or 2 or a diagnosis of myelodysplastic syndrome either intermediate 1 or 2, or high risk by the International Prognostic Scoring System.

- Patients with MDS must be transplant candidates by current clinical standards.

- Patients who have been treated with hypomethylating agents prior to entering the study are eligible.

- Must have matched unrelated donor (8 of 8 HLA match at A, B, C, and DR loci) by high resolution DNA typing

- Must have donor peripheral blood stem cells mobilized by NMDP standards. No bone marrow donors.

- Must have 2-8 x 10^6 CD34+ cells/kg (recipient weight) infused on Day 0.

- Must have at least one additional aliquot of >=1 x 10^6 CD34/kg cryopreserved cells stored at the time of transplant.

- Must receive a myeloablative or reduced intensity conditioning regimen for SCT as defined by the CIBMTR

- Cyclophosphamide and single dose total body irradiation

- Fludarabine and busulfan

- Fractionated TBI and cyclophosphamide

- Busulfan and cyclophosphamide

- Must be able to receive GVHD prophylaxis with tacrolimus and methotrexate.

- Must be = 18 yrs old and = 70 yrs old. Azacitidine is not approved by the FDA for use in children.

- Must have an Eastern Cooperative Oncology Group (ECOG) performance status = 2.

- Must have laboratory results indicating:

- Total bilirubin < 2.0 mg/dl, unless a diagnosis of Gilbert's disease

- AST/ALT = 3 X the upper limit of institutional normal

- Serum creatinine = 2.0 mg/dl

- Patient must have ability to understand and willingness to provide written informed consent prior to participation in the study and any related procedures being performed.

- The effects of azacitidine on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because category D agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of childbearing age must have a negative serum pregnancy test (ß-human chorionic gonadotropin) within 72 hours prior to initiating the conditioning regimen and be willing to not become pregnant by using effective contraception while undergoing treatment and for at least 3 months after the last dose of azacitidine.

- Men must be willing not to father a new child while receiving therapy. They must use an effective barrier method of contraception during the study and for 3 months following the last dose.

Exclusion Criteria:

- Must not have myelofibrosis or other disease known to prolong neutrophil engraftment to > 28 days after transplant.

- Must not be receiving any other investigational agents within 14 days of first dose of azacitidine (Day 7).

- Must not have myeloablative conditioning as defined below:

- TBI < or = Gy +/- purine analog

- Flu + Cy +/- ATG

- Flu + AraC + Ida

- Cladribine + AraC

- Total Lymphoid Irradiation + ATG

- Must not receive antithymocyte globulin as part of pre-transplant conditioning regimens. Antithymocyte globulin is excluded due to its potential impact on modulating the incidence of GvHD or GvL.

- Must not have uncontrolled intercurrent illness including ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.

- Must not be pregnant or breastfeeding. Pregnant women are excluded from this study because azacitidine is a Category D agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with azacitidine, breastfeeding should be discontinued if the mother is treated azacitidine. These potential risks may also apply to other agents used in this study.

- Must not have a known or suspected hypersensitivity to azacitidine, mannitol, or compounds of similar composition to azacitidine..

- Must not have an advanced malignant hepatic tumor.

- Must not be HIV, HBV, or HCV positive.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Azacitidine


Locations

Country Name City State
United States Washington University School of Medicine Saint Louis Missouri

Sponsors (4)

Lead Sponsor Collaborator
Washington University School of Medicine Barnes Jewish Health Foundation, National Cancer Institute (NCI), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Phase I: to Determine the Maximum Tolerated Dose (MTD) of Azacitidine in Patients Undergoing Matched (8 Out of 8) Unrelated Donor Transplant for Any Hematological Malignancy in Remission or With Stable Disease. The MTD is defined as the dose level immediately below the dose level at which patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity. 28 days
Primary Phase II: Number of Participants With Grades II-IV Acute GvHD GVHD rate and severity will be assessed based on modified Glucksberg criteria. Grade II-IV and III-IV aGVHD in first 180 days after transplant will be assessed. Day +180
Secondary Rate of Grades III-IV aGVHD at Day +180. GVHD rate and severity will be assessed based on modified Glucksberg criteria. Day +180
Secondary Overall Survival as Measured by Number of Participants Alive at 1 Year After Transplant Date of transplant to the date of death from any cause. One year after transplant
Secondary Treatment-related Mortality Death that results from a transplant procedure-related complication (e.g. infection, organ failure, hemorrhage, GVHD) rather than from relapse of the underlying disease or an unrelated cause. Day +140
Secondary Number of Participants Who Relapsed Within the First Year of Transplant Recurrence of the original malignant disease after transplantation. The time to relapse is the time to the first observation of hematologic, radiographic, or cytogenetic changes, which result in characterization as relapse. Within the first year of transplant
Secondary Rate of Chronic GvHD One year after transplant
See also
  Status Clinical Trial Phase
Recruiting NCT05400122 - Natural Killer (NK) Cells in Combination With Interleukin-2 (IL-2) and Transforming Growth Factor Beta (TGFbeta) Receptor I Inhibitor Vactosertib in Cancer Phase 1
Terminated NCT04313881 - Magrolimab + Azacitidine Versus Azacitidine + Placebo in Untreated Participants With Myelodysplastic Syndrome (MDS) Phase 3
Recruiting NCT05088356 - Reduced Intensity Allogeneic HCT in Advanced Hematologic Malignancies w/T-Cell Depleted Graft Phase 1
Recruiting NCT04003220 - Idiopathic Chronic Thrombocytopenia of Undetermined Significance : Pathogenesis and Biomarker
Completed NCT02916979 - Myeloid-Derived Suppressor Cells and Checkpoint Immune Regulators' Expression in Allogeneic SCT Using FluBuATG Phase 1
Active, not recruiting NCT03755414 - Study of Itacitinib for the Prophylaxis of Graft-Versus-Host Disease and Cytokine Release Syndrome After T-cell Replete Haploidentical Peripheral Blood Hematopoietic Cell Transplantation Phase 1
Completed NCT00003270 - Chemotherapy, Radiation Therapy, and Umbilical Cord Blood Transplantation in Treating Patients With Hematologic Cancer Phase 2
Recruiting NCT04904588 - HLA-Mismatched Unrelated Donor Hematopoietic Cell Transplantation With Post-Transplantation Cyclophosphamide Phase 2
Terminated NCT04866056 - Jaktinib and Azacitidine In Treating Patients With MDS With MF or MDS/MPN With MF. Phase 1/Phase 2
Recruiting NCT04701229 - Haploinsufficiency of the RBM22 and SLU7 Genes in Del(5q) Myelodysplastic Syndromes
Suspended NCT04485065 - Safety and Efficacy of IBI188 With Azacitidine in Subjects With Newly Diagnosed Higher Risk MDS Phase 1
Recruiting NCT04174547 - An European Platform for Translational Research in Myelodysplastic Syndromes
Enrolling by invitation NCT04093570 - A Study for Participants Who Participated in Prior Clinical Studies of ASTX727 (Standard Dose), With a Food Effect Substudy at Select Study Centers Phase 2
Completed NCT02508870 - A Study of Atezolizumab Administered Alone or in Combination With Azacitidine in Participants With Myelodysplastic Syndromes Phase 1
Completed NCT04543305 - A Study of PRT1419 in Patients With Relapsed/Refractory Hematologic Malignancies Phase 1
Recruiting NCT05384691 - Efficacy of Luspatercept in ESA-naive LR-MDS Patients With or Without Ring Sideroblasts Who do Not Require Transfusions Phase 2
Recruiting NCT05365035 - A Phase II Study of Cladribine and Low Dose Cytarabine in Combination With Venetoclax, Alternating With Azacitidine and Venetoclax, in Patients With Higher-risk Myeloproliferative Chronic Myelomonocytic Leukemia or Higher-risk Myelodysplastic Syndromes With Excess Blasts Phase 2
Recruiting NCT06008405 - Clinical Trial Evaluating the Safety of the TQB2928 Injection Combination Therapy Phase 1
Not yet recruiting NCT05969821 - Clonal Hematopoiesis of Immunological Significance
Withdrawn NCT05170828 - Cryopreserved MMUD BM With PTCy for Hematologic Malignancies Phase 1