Comparing Cyclophosphamide and Abatacept With Standard of Care Treatment Following Stem Cell Transplantation

Hematologic Neoplasms Clinical Trial

Official title:

A Randomized Phase II Trial Comparing a Calcineurin Inhibitor-free Graft-versus-host Disease Prophylaxis Regimen With Post-transplantation Cyclophosphamide and Abatacept to Standard of Care

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03680092
• Other study ID #: 180383
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 26, 2019
• Est. completion date: December 2027

Study information

• Verified date: April 2024
• Source: University of California, San Diego
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to investigate whether the combination of cyclophosphamide and abatacept versus the treatment used in standard of care will reduce the incidence of moderate and severe chronic graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation. GVHD occurs when the cells from your donor (the graft) see your body's cells (the host) as different and attack them.

Description:

The experimental GVHD prophylaxis arm consists of cyclophosphamide and abatacept. Cyclophosphamide induces apoptosis of activated T cells and abatacept (CTLA4Ig) blocks activation of T cells by inhibiting the co-stimulatory signal.

Compared to the standard-of-care control arm, the experimental arm is much more convenient and expected to be associated with fewer toxicities.

In addition there is a great theoretical potential for immunological synergy between cyclophosphamide and abatacept for inducing post-transplant immunologic tolerance that clinically might translate into less GVHD without increase in relapse Patients will be randomized 1:1 to the experimental vs the standard of care arm. Randomization will be done prior to the use of any conditional therapy.

The two arms will be stratified by disease (acute leukemia vs others) and donor type (MRD vs MUD/MUD vs Haplo) in an effort to keep them balanced.

The conditioning regimen for both arms will be mainly Busulfan/Fludarabine (A Total Body Irradiation based conditioning regimen will be allowed for diseases such as ALL)

The GVHD prophylaxis regimen on the experimental arm will consist of high dose Cyclophosphamide on Days +3 and +4 followed by abatacept for 6 months.

The GVHD prophylaxis regimen on the standard of care arm will consist of methotrexate on Days +1,+3, +6 and +11 and tacrolimus for patients with a 10/10 matched related or unrelated donor and of high dose cyclophosphamide on Days +3 and +4 followed by tacrolimus and mycophenolate for patients with a haploidentical donor.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 43
• Est. completion date: December 2027
• Est. primary completion date: June 8, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• High risk hematologic malignancy justifying the need for an allogeneic hematopoetic stem cell transplantation: AML, ALL, CML in accelerated or blast phase, MDS/MPN, NHL, Hodgkin lymphoma, and multiple myeloma

• Creatinine clearance > 40

• Adequate hepatic function

• Normal cardiac function (EF > 50%)

Exclusion Criteria:

• Patients with hematologic malignancies for which transplant is not the only curative option, such as AML with good or intermediate cytogenetics or molecular markers in CR1 or CML in chronic phase

• Inability to identify an 10/10 HLA-Matched Donor (related or unrelated) or a haploidentical donor

• Active malignant disease relapse

• Active, uncontrolled infection, uncontrolled cardiac angina, symptomatic congestive heart failure

• Life expectancy <3 months

• Pregnancy or lactation

• Patients may not be receiving any other investigational agents in the last 28 days

• Patients with chronic myeloid leukemia in first chronic phase

Related Conditions & MeSH terms

• GVHD
• Hematologic Neoplasms

Intervention

Drug:
• Cyclophosphamide
Day 3 and day 4 following transplant. Dosing will be based on patients' actual weight up to 120% of ideal body weight, above which it will be based on adjusted ideal body weight (ideal weight plus 50% of the difference between ideal and actual weight).
• abatacept
Abatacept at a dose of 10mg/kg will be administered on days +5, +14 and +28, +56, +84, +112, +140, +168
• Methotrexate
standard of care Methotrexate 5 mg/m2 on Days 1, 3, 6 and 11
• Tacrolimus
Tacrolimus per institutional guidelines

Locations

Country	Name	City	State
United States	UC San Diego Moores Cancer Center	La Jolla	California

Sponsors (2)

Lead Sponsor	Collaborator
Dimitrios Tzachanis, MD PhD	Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	occurrence of moderate and severe chronic GVHD at one year post transplant	The occurrence of moderate and severe chronic GVHD at one year post Chronic GVHD will be diagnosed and staged according to the previously published and widely accepted National Institutes of Health consensus criteria	through study completion, an average of 1 year
Secondary	GVHD- and relapse- free survival by one year post transplant	GVHD- and relapse- free survival will be defined as the absence of acute GVHD Grade III or IV or moderate or severe chronic GVHD or relapse or non-relapse mortality by one year post transplant. Acute GVHD will be diagnosed and graded according to Glucksberg criteria	through study completion, an average of 1 year