Brentuximab Vedotin Prevention of (GVHD) After Unrelated Allogeneic Stem Cell Transplantation

NCT01700751 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 201211047
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot clinical trial studies the safety and maximum tolerated dose of brentuximab vedotin when given with tacrolimus and methotrexate after unrelated allogeneic donor stem cell transplant in patients with acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndromes. The addition of brentuximab vedotin to tacrolimus and methotrexate may result in a significant reduction of graft versus host disease in these patients.

Conditions

Leukemia, Acute Myeloid; Leukemia, Lymphoblastic,Acute; Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (1)

• MTD of brentuximab vedotin when administered with a GVHD prophylaxis regimen

  Defined as the dose level immediately below the dose level at which 2 patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity; Hematologic DLT is defined as ANC \< 500/mm3 for three consecutive days beyond Day +21 that was determined by the investigator to be likely related to brentuximab vedotin. Non-hematologic DLT is defined as any grade 3 or higher non-hematologic toxicity that was determined by the investigator to be possibly, probably, or definitely related to brentuximab vedotin, with the following specific exceptions: * Grade 3 or 4 nausea, vomiting, diarrhea, mucositis, or fatigue thought to be associated with conditioning regimens * Grade 3 rash will only be considered a DLT for patients who have received two weeks of supportive care treatment with no improvement.

  37 days

Secondary Outcomes (9)

• Safety and tolerability of brentuximab vedotin when administered with a GVHD prophylaxis regimen

  100 days

• Rate of acute GVHD

  100 days

• Rate of chronic GVHD

  2 years

• Progression-free survival

  2 years

• Overall survival.

  2 years

Study Arms (5)

Dose Level 0 (starting dose)

EXPERIMENTAL

brentuximab vedotin 0.3mg/kg, given IV on Days 7, 28, 49 \& 70

Drug: brentuximab vedotin

Dose Level 1

EXPERIMENTAL

brentuximab vedotin 0.6mg/kg, given IV on Days 7, 28, 49 \& 70

Drug: brentuximab vedotin

Dose Level 2

EXPERIMENTAL

brentuximab vedotin 1.2mg/kg, given IV on Days 7, 28, 49 \& 70

Drug: brentuximab vedotin

Dose Level 3

EXPERIMENTAL

brentuximab vedotin 1.8mg/kg, given IV on Days 7, 28, 49 \& 70

Drug: brentuximab vedotin

Control Dose Level

NO INTERVENTION

The first 3 patients will not receive brentuximab vedotin.

Interventions

brentuximab vedotin DRUG

Also known as: Adcetris

Dose Level 0 (starting dose); Dose Level 1; Dose Level 2; Dose Level 3

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must be scheduled to undergo stem cell transplantation for one of the following diagnoses:
• acute myeloid leukemia (AML) in CR1 (first complete remission, CR or CRi) or CR2 (second complete remission, CR or CRi),
• acute lymphoblastic leukemia (ALL) in CR1 or CR2 (CR or CRi)
• myelodysplastic syndrome (MDS) without progression to AML.
• Chronic myelogenous leukemia (CML)
• Non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD)
• Chronic lymphocytic leukemia (CLL)
• Multiple myeloma (MM)
• Patients must be the recipient of unrelated donor peripheral blood stem cell products. Mismatches at both antigen and allele level will be eligible. Match must be 6 or 7 out of 8 loci (HLA A, B, C, and DRB1).
• Patient must receive any one of the following conditioning regimens: total body radiation (single or fractionated dose)/cyclophosphamide, busulfan/ cyclophosphamide, or fludarabine/busulfan/lymphocyte immune globulin (ATGAM/thymo).
• Patient must be ≥ 18 years and ≤ 70 years of age.
• Patient must have an ECOG performance status ≤ 2 or Karnofsky performance scale ≥ 60%
• Patient must have CD34+ stem cells ≥ 2x106/kg (actual body weight of the recipient) available for transplantation.
• Patient must have appropriate organ function as defined below (this criterion should be met on screening and on the day of the first dose of brentuximab vedotin (as assessed prior to dosing)):
• Total bilirubin ≤ 2.0 x IULN

You may not qualify if:

• Patient must not have had prior exposure to brentuximab vedotin.
• Patient must not have a history of other malignancy that has not been in remission for at least 3 years, with the exception of basal non-melanoma skin cancer which were treated with local resection only or intraepithelial lesions or carcinoma in situ of the cervix or prostate that has been curatively treated.
• Patient must not be receiving any other investigational agents.
• Patient must not have active CNS involvement.
• Patient must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to brentuximab vedotin or other agents used in the study.
• Patients must not have had previous radiation therapy to the mediastinum or lungs.
• Patient must not have an uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, active pulmonary diseases, or psychiatric illness/social situations that would limit compliance with study requirements (this criterion should be met on screening and on the day of but prior to first dose of brentuximab vedotin).
• Patient must not be pregnant and/or breastfeeding.
• Patient must not be known to be HIV-positive on combination antiretroviral therapies.
• Patient must not have had a previous allogeneic or syngeneic transplant. Prior autologous transplant is allowed.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Seagen Inc.: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes

Interventions

Brentuximab Vedotin

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Study Officials

• Mark Schroeder, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2012
• First Posted: October 4, 2012
• Study Start: February 25, 2013
• Primary Completion: November 11, 2015
• Study Completion: November 21, 2016
• Last Updated: April 16, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)