Acute Lymphocytic Leukemia, Acute Myelogenous Leukemia, Chronic Lymphocytic Leukemia, Chronic Myelogenous Leukemia, Hodgkin Lymphoma, Multiple Myeloma, Myelodysplastic Syndrome, Non-Hodgkin Lymphoma
Conditions
Brief summary
This is a phase I single center dose escalation study with an extension at the best available dose to determine the tolerability of inducible regulatory T cells (iTregs) when given to adult patients undergoing non-myeloablative HLA-identical sibling donor peripheral blood stem cell (PBSC) transplantation for the treatment of a high risk malignancy. Up to 5 dose cohorts will be tested. Once the tolerable dose is determined for iTregs, enrollment will continue with an additional 10 patients using sirolimus/Mycophenolate mofetil (MMF) graft-versus-host disease (GVHD) prophylaxis to gain further safety information and to provide pilot data in this treatment setting.
Detailed description
Co-enrollment in University Of Minnesota protocol MT2001-10 is required and transplantation will be according to that protocol with iTregs administered the morning of day 0 followed no sooner than 4 hours later by the PBSC transplantation.
Interventions
BIOLOGICALiTreg
The iTregs will be infused at the assigned dose without a filter or pump slowly by gravity over 15-60 minutes. The iTregs should be given at least 4 hours before the peripheral blood stem cell (PBSC) infusion (MT2001-10).
Sponsors
Masonic Cancer Center, University of Minnesota
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 18 - 75 years of age with an HLA-identical sibling donor * One of the following disease categories: * Acute myelogenous leukemia - high risk CR1 (as evidenced by preceding MDS, intermediate to high risk cytogenetics, ≥ 2 cycles to obtain CR, erythroblastic or megakaryocytic leukemia; CR2+. All patients must be in CR as defined by hematological recovery (ANC \> 0.5x 109/L), AND \<5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%. * Acute lymphocytic leukemia - high risk CR1 \[t(9;22), t (1:19), t(4;11) or other MLL rearrangements\] or \>1cycle to obtain CR; CR2+. All patients must be in CR as defined by hematological recovery (ANC \> 0.5x 109/L), AND \<5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%. * Chronic myelogenous leukemia all types except blast crisis (note treated blast crisis in chronic phase is eligible) * Non-Hodgkin lymphoma or Hodgkin lymphoma demonstrating chemosensitive disease * Myelodysplastic syndrome with severe pancytopenia, leading to either transfusion dependency or increased risk for infections * Performance status: Karnofsky ≥ 60% * Adequate organ function within 28 days of study enrollment defined as: * Liver: SGOT and SGPT \< 5.0 x ULN; total bilirubin \< 3 x ULN * Renal: serum creatinine \< 2.0 mg/dl or glomerular filtration rate (GFR) \> 40 mL/min/1.73m2. Patients with a creatinine \> 1.2 mg/dl or a history of renal dysfunction must have glomerular filtration rate (GFR) \> 40 mL/min/1.73m2 * Albumin: \> 2.5 g/dL * Cardiac: No decompensated CHF or uncontrolled arrhythmia; ejection fraction \> 35% within 6 weeks prior to study enrollment * Pulmonary: No O2 requirements; DLCO \> 30% predicted within 6 weeks prior to study enrollment * If recent mold infection (e.g. aspergillus) must have minimum of 30 days of therapy and responsive disease and be cleared by Infectious Disease * Sexually active females of child bearing potential and males must agree to use effective contraception for the duration of the transplant period * Voluntary written consent
Exclusion criteria
* Pregnancy or breast feeding - women of childbearing potential must have a negative pregnancy test within 28 days of study enrollment. * Prior myeloablative transplant within previous 3 months of study enrollment. * Evidence of HIV infection or known HIV positive serology. * Active serious infection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of grade 3-5 infusional toxicity | Within 48 Hours After iTregs Administration | Targeted adverse events and unexpected events not explained by the PBSCT or disease will be collected \[(1-4 hours after the iTreg infusion and before the PBSCT at day 0) and 24 hours and 48 hours after the iTreg infusion (+/- 2 hours)\] |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) | Day 100 | Graft-versus-host disease (GVHD) is a complication that can occur after a stem cell or bone marrow transplant in which the newly transplanted material attacks the transplant recipient's body. Abstracted from the routine clinical data collected for the primary transplant protocol (MT2001-10). |
| Incidence of chronic graft-versus-host disease (GVHD) | 12 Months | Graft-versus-host disease (GVHD) is a complication that can occur after a stem cell or bone marrow transplant in which the newly transplanted material attacks the transplant recipient's body. Abstracted from the routine clinical data collected for the primary transplant protocol (MT2001-10). |
| Relapse of Disease | 12 Months | The return of signs and symptoms of a disease after a remission. |
| Survival | 1 Year | Number (count) of patients alive at 1 year after treatment. |
Countries
United States
Outcome results
None listed