Clinical trial · Interventional

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

A Study to Infuse ROR1-Specific Autologous T Cells for Patients With Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL)

NCT02194374CI-TRIAL-00028069withdrawnPhase 1ClinicalTrials.gov clinicaltrialsPublishedExplore in graph →

Why stopped (as posted): Study closed with no enrollment due to unavailability of reagent.

Summary

Brief summary (as posted)

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

Conditions (1)

Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.

Condition (as posted)	Mapped entity	Match	Confidence
Leukemia	Leukemia	ONTOLOGY_EXACT	0.90

Interventions

Interventions (5)

Intervention	Type	Mapped drug	Match
Bendamustine	Drug	Bendamustine	ALIAS
Cyclophosphamide	Drug	Cyclophosphamide	ALIAS
Fludarabine	Drug	Fludarabine	ALIAS
Rituximab	Drug	Rituximab	ALIAS
ROR1R-CAR-T Cell Infusion	Procedure	—	UNRESOLVED

Design

Arms and outcomes

Arms (1)

type
EXPERIMENTAL
label
ROR1R-CAR-T Cells
description
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.
interventionNames
1. Procedure: ROR1R-CAR-T Cell Infusion
2. Drug: Fludarabine
3. Drug: Cyclophosphamide
4. Drug: Rituximab
5. Drug: Bendamustine

Primary outcomes (1)

measure
Maximum Tolerated Dose (MTD) of ROR1R-CAR-T Cells for Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL)
timeFrame
4 weeks
description

Eligibility

Eligibility (as posted)

Sex: All
Minimum age: 18 Years
Maximum age: 85 Years

Show eligibility criteria text

Inclusion Criteria:

1. Patients with B cell CLL/SLL, age \</= 85 years old, who have active disease that meets 2008 IWCLL/NCI-WG criteria to initiate treatment.
2. 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.
3. At least 21 days from last cytotoxic chemotherapy.
4. Eastern Cooperative Oncology Group Performance Status (ECOG PS) \<2.
5. 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.
6. Adequate renal function, defined as serum creatinine \<2 x ULN.
7. Able to provide written informed consent, and agree to practicing 2 forms of birth control during the study.
8. 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%.

Exclusion Criteria:

1. Surface ROR1 expression by \<5% of CLL cells.
2. 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.
3. Patients with known systemic allergy to bovine or murine products.
4. Known positive serology for human immunodeficiency virus (HIV) or human anti-mouse antibody (HAMA).
5. Active, uncontrolled autoimmune phenomenon autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura (AIHA, ITP) requiring steroid therapy.
6. Presence of \>/= Grade 3 non-hematologic toxicity common terminology criteria (CTC) version 4 from the previous treatment.
7. Concurrent use of investigational therapeutic agent.
8. Prior allogeneic hematopoietic stem-cell transplantation if evidence of donor chimerism persists. Patients with exclusively autologous hematopoiesis are eligible.
9. Refusal to participate in the long-term follow-up protocol (2006-0676).

References

Publications (0)

Data not yet available

No reference posted for this study.

Registry

Dates and enrollment

Start: Jan 1, 2015
Primary completion: Jun 1, 2017
Completion: Jun 1, 2017
First posted: Jul 18, 2014
Last update posted: Jun 12, 2017
Enrollment: 0 (actual)
Lead sponsor: M.D. Anderson Cancer Center OTHER
Collaborators: CLL Global Research Foundation Alliance
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

Data updated 22 days agoSource updated Jun 12, 2017source: clinicaltrials

Locations

Locations by country (0)

No location posted.

Trial listing is informational. Eligibility is decided by the study team; contact information is on ClinicalTrials.gov.