Cytokine-Treated Veto Cells in Treating Patients With Hematologic Malignancies Following Stem Cell Transplant

• Register: ClinicalTrials.gov
• Last refreshed on: 27 February 2024
• Main ID: NCT03622788
• Date of registration: 03/08/2018
• Prospective Registration: Yes
• Primary sponsor: M.D. Anderson Cancer Center
• Public title: Cytokine-Treated Veto Cells in Treating Patients With Hematologic Malignancies Following Stem Cell Transplant
• Scientific title: Anti-Viral Central Memory CD8 Veto Cells in Haploidentical Hematopoietic Stem Cell Transplantation
• Date of first enrolment: August 8, 2019
• Target sample size: 24
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03622788
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

United States

Contacts

• Name: Richard E. Champlin

• Name: Richard E Champlin
• Affiliation: M.D. Anderson Cancer Center

Key inclusion & exclusion criteria

Patient Inclusion Criteria:

- Age 12-75 years. The first 3 subjects will be 18 years of age to gain experience and
observe safety. After 3 adult subjects have successfully engrafted and if the safety
profile is tolerable, adolescents age 12 may be enrolled on to the trial

- Patients with a diagnosis either follicular lymphoma (FL), mantle cell lymphoma (MCL),
chronic lymphocytic leukemia (CLL), multiple myeloma (MM), Hodgkin's lymphoma (HL),
non-Hodgkin's lymphoma (NHL), chronic myeloid leukemia (CML), myelodysplastic
syndrome, myeloproliferative syndromes (MPD), acute myeloid leukemia (AML) or acute
lymphoid leukemia (ALL).

- Patients with aplastic anemia and severe immune deficiency or nonmalignant bone marrow
failure states. Patients with severe thalassemia requiring regular blood transfusions
or sickle cell disease with severe clinical features (these include any clinically
significant sickle genotype, for example, hemoglobin SS (Hb SS), hemoglobin SC (Hb
SC), hemoglobin S beta thalassemia (Hb Sbeta), or Hemoglobin S-OArab genotype] with at
least one of the following manifestations:

- Clinically significant neurologic event (stroke) or neurological deficit lasting
> 24 hours;

- History of two or more episodes of acute chest syndrome (ACS) in the 2-year
period preceding enrollment or referral despite adequate supportive care measures
(i.e. asthma therapy);

- An average of three or more pain crises per year in the 2-year period preceding
enrollment or referral (required intravenous pain management in the outpatient or
inpatient hospital setting);

- Administration of regular red blood cell (RBC) transfusion therapy, defined as 8
or more transfusion events per year (in the 12 months before enrollment) to
prevent vaso-occlusive clinical complications (i.e. pain, stroke, or acute chest
syndrome);

- An echocardiographic finding of tricuspid valve regurgitant jet (TRJ) velocity >=
2.7 m/sec.

- Ongoing high impact1 chronic pain on a majority of days per month for >= 6 months
as defined as ONE or more of the following: Chronic pain without contributory
sickle cell disease (SCD) complications2, OR mixed pain type in which chronic
pain is occurring at site(s) (arms, back, chest, or abdominal pain) unrelated to
any sites associated with contributory SCD complications2 (e.g. leg ulcers and/or
avascular necrosis)

- Patients with hematological malignancies must have had persistent or progressive
disease despite initial chemotherapy and must have achieved stable disease or a
partial or complete response to their most recent chemotherapy. Patients with low bulk
or indolent relapse are eligible without additional treatment. Patients with high-risk
acute myeloid leukemia by European LeukemiaNet (ELN) criteria in first remission are
eligible.

- Availability of a medically acceptable haploidentical related donor, age 12-70 years.

- Karnofsky performance status >= 70%.

- Left ventricular ejection fraction of at least 40%.

- Pulmonary function test (PFT) demonstrating an adjusted diffusion capacity of least
50% predicted value for hemoglobin concentration.

- Serum creatinine =< 1.5 mg/dl.

- Serum glutamic-pyruvic transaminase (SGPT) =< 200 IU/ml.

- Bilirubin < 1.5 mg/dl (unless Gilbert's syndrome).

- Negative pregnancy test in a woman with childbearing potential.

Patient Exclusion Criteria:

- Human immune deficiency virus (HIV) seropositive.

- Uncontrolled infection or serious medical or psychiatric condition that would limit
tolerance to the protocol treatment.

- Active central nervous system (CNS) malignancy.

- Availability of medically eligible, human leukocyte antigen (HLA)-matched related stem
cell donor.

Donor Inclusion Criteria

- Medically acceptable haploidentical donor age 12-70 years.

- Hemoglobin > 12.0 g/dL [female] or > 13.0 g/dL [male] or > 11.0 g/dL for females of
childbearing potential with documented iron deficiency anemia

- Platelet count 150, 0000/ul

- WBC 3.0 - 11.0 K/ul

- No anomalies on CBC and differential indicating a hematopoietic disorder

- Negative pregnancy test for women of childbearing potential; Not lactating

- Systolic blood pressure < 170 mmHg and Diastolic blood pressure < 95 mmHg

- Performance status KPS > 70%

- CXR negative for active infection or malignancy

- EKG not suggestive of uncontrolled cardiac disease

- No known allergy to cytokines if cytokines are to be used.

- No active or uncontrolled autoimmune disorders

- Completion and signature of donor questionnaire (within 30 days)

- Donor infectious disease panel and health assessment performed by attending physician

Donor Exclusion Criteria

- Individuals with cognitive impairments and/or any serious unstable pre-existing
condition or psychiatric disorder that can interfere with safety or without obtaining
informed consent or compliance with study procedures.



Age minimum: 12 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Bone Marrow Failure

Hodgkin Lymphoma

Acute Myeloid Leukemia

Chronic Lymphocytic Leukemia

Plasma Cell Myeloma

Follicular Lymphoma

Myeloproliferative Neoplasm

Chronic Myelogenous Leukemia, BCR-ABL1 Positive

Non-Hodgkin Lymphoma

Acute Lymphoblastic Leukemia

Aplastic Anemia

Mantle Cell Lymphoma

Myelodysplastic Syndrome

Intervention(s)

Procedure: Peripheral Blood Stem Cell Transplantation

Biological: Anti-Thymocyte Globulin

Biological: Cytokine-treated Veto Cells

Drug: Fludarabine

Radiation: Total-Body Irradiation

Drug: Cyclophosphamide

Primary Outcome(s)

Efficacy of veto cells [Time Frame: At day 42 post cytokine-treated veto cell infusion]

Optimal dose of donor-derived cytokine-treated veto cells [Time Frame: Within 42 days of cytokine-treated veto cell infusion]

Secondary Outcome(s)

Response rate [Time Frame: Up to 1 year]

Infections [Time Frame: Up to 1 year]

Immune reconstitution [Time Frame: Up to 1 year]

Time to progression [Time Frame: Up to 1 year]

Overall survival [Time Frame: Up to 1 year]

Incidence of adverse events [Time Frame: Up to 1 year]

Secondary ID(s)

NCI-2018-01557

2018-0221

Source(s) of Monetary Support

Please refer to primary and secondary sponsors