Autologous ROR1R-CAR-T Cells for Chronic Lymphocytic Leukemia (CLL)

NCT02194374 | Withdrawn Phase 1

• 2 other identifiers: 2012-0932NCI-2014-01715
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Gene transfer is a process in which the DNA (genetic material) of certain cells is changed. In this study, gene transfer will be performed on a type of white blood cell (called T cells) to recognize leukemia cells in the same person the T cells were collected from. The goal of this clinical research study is to learn if it is safe to give these genetically-changed T cells back to patients with CLL/SLL. Researchers also want to learn if these cells can help to attack CLL/SLL cells.

Conditions

Leukemia

Keywords

Leukemia; Chronic lymphocytic leukemia; CLL; Small lymphocytic lymphoma; SLL; B cell; ROR1-specific T cells; Fludarabine; Fludarabine Phosphate; Fludara; Cyclophosphamide; Cytoxan; Neosar; Rituximab; Rituxan; Bendamustine; Bendamustine Hydrochloride; Bendamustine HCL; CEP-18083; SDX-105; Treanda

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of ROR1R-CAR-T Cells for Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL)

  MTD defined as highest dose level in which 6 subjects have been treated with at most 1 subject experiencing ROR1R-CAR-T cell-related dose limiting toxicity (DLT). DLT defined as the following: * Common Toxicity Criteria for Adverse Effects (CTCAE) Grade ≥ 3 organ toxicity (cardiac, dermatologic, gastrointestinal, hepatic, pulmonary, renal/genitourinary, or neurologic) not pre-existing or due to underlying malignancy and occurring within 30 days of study product infusion. * CTCAE Grades 3-5 allergic reactions related to study cell infusion. * CTCAE Grade ≥ 2 autoimmune reaction related to study product infusion. * Treatment-related death within 8 weeks of study product infusion.

  4 weeks

Study Arms (1)

ROR1R-CAR-T Cells

EXPERIMENTAL

Peripheral blood mononuclear cells (PBMC) collected via venipuncture and/or steady state leukapheresis at discretion of PI. Participants receive a cycle of lympho-depleting chemotherapy as chosen by treating physician 4 to 5 days before ROR1R-CAR-T cell infusion : Fludarabine, Cyclophosphamide, and Rituximab (FCR), Bendamustine and Rituximab (BR), or Fludarabine, Bendamustine, and Rituximab (FBR). Dose Escalation Cohort starting dose level of ROR1R-CAR-T cells/kg: 105 cell/kg infused via central venous catheter or by vein on Day 1. Dose Expansion Cohort starting dose level of ROR1R-CAR-T cells/kg: MTD from Dose Escalation Cohort.

Procedure: ROR1R-CAR-T Cell Infusion; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Rituximab; Drug: Bendamustine

Interventions

ROR1R-CAR-T Cell Infusion PROCEDURE

Dose Escalation Cohort starting dose level of ROR1R-CAR-T cells/kg: 105 cell/kg infused via central venous catheter or by vein on Day 1. Dose Expansion Cohort starting dose level of ROR1R-CAR-T cells/kg: MTD from Dose Escalation Cohort.

ROR1R-CAR-T Cells

Fludarabine DRUG

FCR Regimen: 25 mg/m2 by vein on Days -5, -4, and -3. FBR Regimen: 20 mg/m2 by vein Days -5, -4, and -3.

Also known as: Fludarabine Phosphate, Fludara

ROR1R-CAR-T Cells

Cyclophosphamide DRUG

FCR Regimen : 250 mg/m2 by vein on Days -5, -4, and -3.

Also known as: Cytoxan, Neosar

ROR1R-CAR-T Cells

Rituximab DRUG

FCR and FBR Regimen: 375-500 mg/m2 by vein on Day -5. BR Regimen: 375-500 mg/m2 by vein on Day -4.

Also known as: Rituxan

ROR1R-CAR-T Cells

Bendamustine DRUG

BR Regimen: 70-90 mg/m2 by vein on Days -4 and -3. FBR Regimen: 30-50 mg/m2 by vein on Days -5 to -3.

Also known as: Bendamustine Hydrochloride, Bendamustine HCL, CEP-18083, SDX-105, Treanda

ROR1R-CAR-T Cells

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with B cell CLL/SLL, age \</= 85 years old, who have active disease that meets 2008 IWCLL/NCI-WG criteria to initiate treatment.
• Patients who have failed at least one line of a standard treatment, including bendamustine, fludarabine, ibrutinib, or alemtuzumab and require treatment within 2 years of completion of last treatment regimen or untreated patients with del17p by FISH (high-risk) who do not have an allogeneic stem cell transplant option.
• At least 21 days from last cytotoxic chemotherapy.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) \<2.
• Adequate hepatic function, defined as substance glutamate pyruvate transaminase (SGPT) \<3 x upper limit of normal (ULN); serum bilirubin and alkaline phosphatase \<2 x ULN, or considered not clinically significant by the study doctor or designee.
• Adequate renal function, defined as serum creatinine \<2 x ULN.
• Able to provide written informed consent, and agree to practicing 2 forms of birth control during the study.
• Patients must have adequate cardiac function as indicated by New York Heart Association (NYHA) classification I or II AND left ventricular ejection fraction of \>40% and adequate pulmonary function as indicated by room air oxygen saturation of \>94%.

You may not qualify if:

• Surface ROR1 expression by \<5% of CLL cells.
• Positive beta-HCG in female of child-bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization or lactating females.
• Patients with known systemic allergy to bovine or murine products.
• Known positive serology for human immunodeficiency virus (HIV) or human anti-mouse antibody (HAMA).
• Active, uncontrolled autoimmune phenomenon autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura (AIHA, ITP) requiring steroid therapy.
• Presence of \>/= Grade 3 non-hematologic toxicity common terminology criteria (CTC) version 4 from the previous treatment.
• Concurrent use of investigational therapeutic agent.
• Prior allogeneic hematopoietic stem-cell transplantation if evidence of donor chimerism persists. Patients with exclusively autologous hematopoiesis are eligible.
• Refusal to participate in the long-term follow-up protocol (2006-0676).

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• CLL Global Research Foundation Alliance: collaborator

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

fludarabine; fludarabine phosphate; Cyclophosphamide; Rituximab; Bendamustine Hydrochloride

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Butyrates; Acids, Acyclic; Carboxylic Acids; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• William G. Wierda, MD, PHD, BS

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: July 16, 2014
• First Posted: July 18, 2014
• Study Start: January 1, 2015
• Primary Completion: June 1, 2017
• Study Completion: June 1, 2017
• Last Updated: June 12, 2017

Record last verified: 2017-06