Phase 1-2 MAHCT w/ TCell Depleted Graft w/ Simultaneous Infusion Conventional and Regulatory T Cell
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|ClinicalTrials.gov Identifier: NCT01660607|
Recruitment Status : Recruiting
First Posted : August 8, 2012
Last Update Posted : April 22, 2019
|Condition or disease||Intervention/treatment||Phase|
|Myeloid Leukemia, Chronic Acute Myelogenous Leukemia Myelodysplastic Syndromes (MDS) Lymphoma, Non-Hodgkin||Biological: Conventional T cells (Tcon) and Regulatory T cells (Treg)||Phase 1 Phase 2|
- To determine the efficacy, safety and feasibility of administration of several dose combinations of conventional T cells (Tcon) and regulatory T cells (Treg) in patients undergoing allogeneic hematopoietic cell transplantation (HCT) with HLA matched donors (related or unrelated) using a T cell depleted graft [CD34+ hematopoietic progenitor cells ("CD34+ HSPC")], without immune suppression.
- To determine the maximum tolerated dose of infused regulatory and conventional T cells in the matched donor setting
- To determine 1 year event free survival (EFS) post HCT
- To determine the 1 year OS in patients undergoing allogeneic HCT with matched donors.
- To measure the incidence and severity of acute and chronic graft vs host disease (GvHD)
- To measure incidence of serious infections
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase 1-2 Trial for Patients With Advanced Hematologic Malignancies Undergoing Myeloablative Allogeneic HCT With a T-cell Depleted Graft With Infusion of Conventional T-cells and Regulatory T-cells|
|Study Start Date :||December 2011|
|Estimated Primary Completion Date :||December 2022|
|Estimated Study Completion Date :||December 2023|
Experimental: Dose escalation
For the Phase I arm of the study the addition of planned numbers and ratios of Treg compared to Tcon will occur at defined time points after hematopoietic cell infusion. Each cohort will have 3 patients per group. The initial doses and ratios utilized will be 1 x 10^6/kg of T reg cells to 3x10^6/kg of Tcon cells at a 1:3 ratio. In order to progress to the next dose level, there must be no evidence of grade 3 or 4 acute GVHD.
Biological: Conventional T cells (Tcon) and Regulatory T cells (Treg)
A baseline cell dose of conventional T cells of 1x10^6/kg will be used with escalation to the maximum tolerated dose up to 1x10^7/kg
Other Name: Purified regulatory T cells
- GvHD free Relapse free Survival (GRFS) [ Time Frame: 12 months ]GvHD-free is defined as no GvHD symptoms, and relapse free survival is defined as survival at 12 months without relapse.
- Dose-limiting toxicity (DLT) [ Time Frame: 28 days ]
Dose-limiting Toxicity (DLT) was assessed as:
- Absolute neutrophil count <500/µL, to 28 day
- Cytokine release syndrome/acute infusion reactions as CTCAE Grade 3 to 5
Grade 3 to 4 acute GvHD. GvHD was staged as follows:
- 1: Skin: rash <25%. Liver: bilirubin (BIL) 2-3mg/dL. Gut: diarrhea (DIA) 500-1000 mL/day
- 2: Skin: rash 25-50%. Liver: BIL 3-6mg/dL. Gut: DIA 1001-1500 mL/day
- 3: Skin: rash > 50%. Liver: BIL 6-15mg/dL. Gut: DIA >1501-2000 mL/day
- 4: Skin: generalized erythroderma. Liver: BIL >15mg/dL. Gut: DIA >2001 mL/day GvHD was graded as follows.
- 1: Skin Stage 1-2; No Liver stage; No Gut stage
- 2: Skin Stage 1-3 ; Liver Stage 1; +/- Gut Stage 1
- 3: Skin Stage 2-3, Liver Stage 2-4; +/- Gut Stage 2-3
- 4: Skin Stage 2-4; Liver Stage 2-4; +/- Gut Stage 2-4 The outcome is reported as the number of participants who received both Treg and Tcon cell infusions and had DLT events, per treatment level, a number without dispersion.
- Overall Survival (OS) [ Time Frame: 1 year ]Overall Survival (OS) at 1 year was assessed as the number of participants per treatment level that received the hematopoietic cell transplant (HCT), and remained alive 12 months later, a number without dispersion.
- Incidence and Severity of Chronic GvHD [ Time Frame: 2 years ]
Incidence and severity of chronic GvHD wil be assessed in participants who received the hematopoietic cell transplant (HCT).
Stage of chronic GvHD was assessed as follows.
- Stage 1: Skin: rash <25% of skin. Liver: bilirubin 2-3mg/dL. Gut: diarrhea 500-1000 mL/day
- Stage 2: Skin: rash 25-50% of skin. Liver: bilirubin 3-6mg/dL. Gut: diarrhea 1001-1500 mL/day
- Stage 3: Skin: rash > 50% of skin. Liver: bilirubin 6-15mg/dL. Gut: diarrhea >1501-2000 mL/day
- Stage 4: Skin: generalized erythroderma. Liver: bilirubin >15mg/dL. Gut: diarrhea >2001 mL/day Grade of chronic GvHD was determined as follows.
- Grade 1: Skin Stage 1-2; No Liver stage; No Gut stage
- Grade 2: Skin Stage 1-3 ; Liver Stage 1; +/- Gut Stage 1
- Grade 3: Skin Stage 2-3, Liver Stage 2-4; +/- Gut Stage 2 to 3
- Grade 4: Skin Stage 2-4; Liver Stage 2-4; +/- Gut Stage 2 to 4 The outcome is reported as the number of participants by cGvHD grade and treatment level, a number without dispersion.
- Incidence of Serious Infections [ Time Frame: 24 months ]The outcome is reported as the number of serious infections per treatment level, in participants who received the hematopoietic cell transplant (HCT), a number without dispersion.
- Concomitant Single-agent Immunosuppression [ Time Frame: 2 years ]During Phase 2, stage 1, concomitant single-agent immunosuppression will be assessed as in participants receiving fresh Treg cells. The outcome is reported as number of such participants who received single-agent immunosuppression, by treatment level, a number without dispersion.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01660607
|Contact: Melanie Gaudinezemail@example.com|
|United States, California|
|Stanford University School of Medicine Palo Alto, California, United States||Recruiting|
|Palo Alto, California, United States, 94305|
|Contact: Melanie Gaudinez 650-725-4983 firstname.lastname@example.org|
|Sub-Investigator: Rajni Agarwal-Hashmi|
|Sub-Investigator: Sally Arai|
|Sub-Investigator: Jonathan Benjamin|
|Sub-Investigator: Laura Johnston|
|Sub-Investigator: Robert Lowsky|
|Sub-Investigator: Robert S Negrin|
|Sub-Investigator: Kevin Sheehan|
|Sub-Investigator: Judith Anne Shizuru|
|Sub-Investigator: David Miklos|
|Sub-Investigator: Wen-Kai Weng|
|Principal Investigator: Everett Meyer|
|Principal Investigator:||Everett Meyer||Stanford University|