Azacytidine Prior to in Vivo T-cell Depleted Allo Stem Cell Transplant for Patients With Myeloid Malignancies in CR

NCT02497404 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 1306014009
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether 5-Azacytidine priming before the conditioning regimen for subjects receiving a hematopoietic stem cell transplant is an effective treatment for high risk myeloid malignancies in complete remission (CR).

Conditions

Leukemia, Erythroblastic, Acute; Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (1)

• Disease Free Survival at 1 Year Post-transplant

  Number of participants without evidence of progression of underlying malignancy for which the transplant was performed, assessed at 1 year post-transplant.

  1 year post-transplant

Secondary Outcomes (8)

• Disease Free Survival at 6 Months Post-transplant

  6 months post-transplant

• Disease Free Survival at 2 Years Post-transplant

  2 years post-transplant

• Overall Survival at 6 Months Post-transplant

  6 months post-transplant

• Overall Survival at 1 Year Post-Transplant

  1 year post-transplant

• Overall Survival at 2 Years Post-Transplant

  2 years post-transplant

Study Arms (1)

5 Azacytidine

EXPERIMENTAL

Patients will be given a five day course of subcutaneous 5-azacytidine, followed by a reduced intensity conditioning regimen of fludarabine and melphalan with or without total body irradiation prior to an allogeneic hematopoietic stem cell transplantation from a related or unrelated HLA matched donor.

Drug: 5-Azacytidine; Drug: Fludarabine; Drug: Melphalan; Drug: Alemtuzumab; Radiation: Total Body Irradiation

Interventions

5-Azacytidine DRUG

Patients will be given a five day course of subcutaneous 5-azacytidine followed by a reduced intensity conditioning regimen of fludarabine and melphalan with or without total body irradiation prior to an allogeneic hematopoietic stem cell transplantation from a related or unrelated HLA matched donor. 5-Azacytidine 75 mg/m2 subcutaneously daily at the same time on days -11, -10, -9, -8 and -7. This will be administered on an outpatient basis if possible.

Also known as: Vidaza

5 Azacytidine

Fludarabine DRUG

Conditioning regimen: Hospital admission will usually take place on the first day of the conditioning regimen. Fludarabine will be given at 40 mg/m2 intravenously daily at the same time over 30 minutes on days -6,-5,-4,-3.

Also known as: Fludara

5 Azacytidine

Melphalan DRUG

Conditioning regimen: Hospital admission will usually take place on the first day of the conditioning regimen. Melphalan will be given at 140 mg/m2 IV on day -3.

Also known as: Alkeran

5 Azacytidine

Alemtuzumab DRUG

Conditioning regimen: Hospital admission will usually take place on the first day of the conditioning regimen. Alemtuzumab will be given at 30 mg subcutaneously on Days -4 and -2 for unrelated donors, and Day -2 for related donors.

Also known as: Campath, Lemtrada

5 Azacytidine

Total Body Irradiation RADIATION

Conditioning regimen: Hospital admission will usually take place on the first day of the conditioning regimen. Total Body Irradiation (TBI) will be given at 2 doses of 200 cGy each on one day of the conditioning regimen (between days -6 and -3).

Also known as: TBI

5 Azacytidine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) as specified below:
• Acute myeloid leukemia with poor risk cytogenetics in complete morphologic remission. These include: del (5q)/-5, del (7q)/-7, abn 3q, 9q, 11q, 20q, 21q, 17p, t(6;9), t(9;22) or complex karyotypes (≥ 3 unrelated abnormalities); or
• Acute myeloid leukemia with either Flt-3, TET-2, p53, DNMT3A, or ASXL1 mutation, mutations of genes involved in the chromatin/spliceosome category (EZH2, SRSF2, U2AF1, ZRSR2), BCOR, and RUNX1, as well as MLL rearrangement, EVI1 overexpression in complete morphologic remission; or
• Acute myeloid leukemia with a white blood cell count of greater than or equal to 50,000/mcL at presentation in first complete morphologic remission; or
• Acute myeloid leukemia in first complete morphologic remission, having required more than one course of induction chemotherapy to attain remission status; or
• Acute myeloid leukemia, all types, excluding M3 (Promyelocytic leukemia) in second or higher complete morphologic remission; or
• Myelodysplastic syndromes (intermediate-2, high risk and chronic myelomonocytic leukemia (CMML) with bone marrow blasts \<5%); or
• Secondary acute myeloid leukemia on the basis of prior MDS or prior myeloproliferative neoplasm (MPN) in complete morphologic remission
• Life expectancy not severely limited by concomitant disease
• Karnofsky Performance Score greater than or equal to 70%.
• Adequate organ function as defined below:
• Serum Bilirubin:\<2.0 mg/dL; Alanine Aminotransferase (ALT) (SGPT): \<3 x upper limit of normal; Creatinine Clearance:\>60 mL/min (eGFR as estimated by the modified Modification of Diet in Renal Disease Study (MDRD) equation)
• \- Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Evidence of chronic active hepatitis or cirrhosis
• HIV infection
• Uncontrolled illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant and lactating women are excluded from the study because the risks to an unborn fetus or potential risks in nursing infants are unknown.
• There are no prior therapies or concomitant medications that would render the patients ineligible

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead

Study Sites (1)

Weill Cornell Medical College

New York, New York, 10021, United States

Location

MeSH Terms

Conditions

Leukemia, Erythroblastic, Acute; Myelodysplastic Syndromes

Interventions

Azacitidine; fludarabine; fludarabine phosphate; Melphalan; Alemtuzumab; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

Leukemia, Myeloid, Acute; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Radiotherapy; Therapeutics; Investigative Techniques

Results Point of Contact

• Title: Sebastian Mayer, MD
• Organization: Weill Cornell Medical College

sam2033@med.cornell.edu

646-962-7950

Study Officials

• Sebastian Mayer, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2015
• First Posted: July 14, 2015
• Study Start: February 13, 2015
• Primary Completion: June 17, 2020
• Study Completion: June 17, 2021
• Last Updated: September 22, 2021
• Results First Posted: September 22, 2021

Record last verified: 2021-08

Locations

US (1)