Clinical Trials /

CAR-37 T Cells In Hematologic Malignancies

NCT04136275

Description:

This research study is studying Chimeric Antigen Receptor (CAR)-37 T Cells (CAR-37 T Cells) for treating people with relapsed or refractory CD37+ hematologic malignancies and to understand the side effects when treated with CAR-37 T Cells. - Chimeric Antigen Receptor (CAR)-37 T Cells (CAR-37 T Cells) is an investigational treatment

Related Conditions:
  • Chronic Lymphocytic Leukemia
  • Diffuse Large B-Cell Lymphoma
  • Follicular Lymphoma
  • High Grade B-Cell Lymphoma, Not Otherwise Specified
  • Mantle Cell Lymphoma
  • Marginal Zone Lymphoma
  • Peripheral T-Cell Lymphoma
  • Primary Cutaneous T Cell Non-Hodgkin Lymphoma
  • Primary Mediastinal B-Cell Lymphoma
  • Small Lymphocytic Lymphoma
  • T-Cell Prolymphocytic Leukemia
  • Transformed Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: CAR-37 T Cells In Hematologic Malignancies
  • Official Title: A Phase I Clinical Trial With CAR-37 T Cells for the Treatment of Patients With Relapsed or Refractory CD37+ Hematologic Malignancies

Clinical Trial IDs

  • ORG STUDY ID: 19-087
  • NCT ID: NCT04136275

Conditions

  • Hematologic Malignancy
  • Leukemia
  • Lymphoma
  • Lymphoma, B-Cell
  • Lymphoma, T-Cell
  • Lymphoma, Non-Hodgkin

Interventions

DrugSynonymsArms
CAR-37 T cellsCAR-37 T cells

Purpose

This research study is studying Chimeric Antigen Receptor (CAR)-37 T Cells (CAR-37 T Cells) for treating people with relapsed or refractory CD37+ hematologic malignancies and to understand the side effects when treated with CAR-37 T Cells. - Chimeric Antigen Receptor (CAR)-37 T Cells (CAR-37 T Cells) is an investigational treatment

Detailed Description

      This is a two-part, non randomized, open label, single site Phase 1 study. Participants who
      fulfill eligibility criteria will be entered into the trial Chimeric Antigen Receptor
      (CAR)-37 T Cells (CAR-37 T Cells).

      This study consists of 2 parts:

        -  Part A (Dose Escalation): The investigators are looking the highest dose of the study
           intervention that can be administered safely without severe or unmanageable side effects
           in participants that have relapsed or refractory CD37+ hematologic malignancies, not
           everyone who participates in this research study will receive the same dose of the study
           intervention. The dose given will depend on the number of participants who have been
           enrolled prior and how well the dose was tolerated

        -  Part B (Expansion Cohort): Part B: Expansion Cohort: Participants will be treated at the
           respective dose (at or below the Maximum Tolerated Dose), as determined during Part A
           (Dose Escalation).

        -  A total of 18 participants will be enrolled to this trial

      This research study is a Phase I clinical trial, which tests the safety of an investigational
      intervention and also tries to define the appropriate dose of the investigational
      intervention to use for further studies.

      Investigational" means that the intervention is being studied The U.S. Food and Drug
      Administration (FDA) has not approved CAR-37 T Cells as a treatment for any disease.

      This is the first time that CAR-37 T Cells will be given to humans
    

Trial Arms

NameTypeDescriptionInterventions
CAR-37 T cellsExperimentalCAR-37 will be administered intravenously on day 0 Enrolled subjects will undergo a leukapheresis procedure processing approximately two times the subject's total blood volume. Subjects will receive 3 days of lymphodepleting chemotherapy starting Day -5, before the infusion of CAR-37 T cells on Day 0
  • CAR-37 T cells
CAR-37 T cells Dose EscalationExperimentalCAR-37 will be administered intravenously on day 0 Enrolled subjects will undergo a leukapheresis procedure processing approximately two times the subject's total blood volume. CAR-37 will undergo dose escalation
  • CAR-37 T cells

Eligibility Criteria

        Inclusion Criteria:

        Voluntarily sign informed consent form.

        Age ≥18 years of at the time of signing informed consent

        Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Karnofsky ≥60%, see
        Appendix A)

          -  Diagnosis of relapsed/refractory (R/R) CD37+ hematologic malignancy as defined as one
             of the following:

          -  Mature B cell neoplasms

               -  Follicular Lymphoma (FL) grade 1, grade 2, or grade 3a

                    -  RR disease after 2 or more prior lines of therapy AND

                    -  1 of the prior lines of therapy must include an anti-CD20 antibody
                       monotherapy.

               -  Marginal Zone Lymphoma (MZL) nodal or extranodal:

                    -  R/R disease after 2 or more prior lines of therapy AND

                    -  1 of the prior lines of therapy must include an anti-CD20 antibody
                       monotherapy

               -  Diffuse large B-cell lymphoma (DLBCL), including transformed follicular lymphoma
                  (FL), primary mediastinal B-cell lymphoma (PMBCL), high-grade B-cell lymphoma and
                  grade 3b Follicular Lymphoma (FL).

                    -  R/R disease after 2 or more prior lines of therapy OR

                    -  Relapsed following autologous SCT,OR

                    -  Ineligible for autologous SCT.

               -  Mantle cell lymphoma

                    -  R/R disease as defined by disease progression after last regimen (including
                       autologous SCT), OR Refractory disease as defined as failure to achieve a CR
                       to last regimen.

                    -  Prior therapy must include:

                         -  Anthracycline or bendamustine-containing chemotherapy AND

                         -  Anti-CD20 monoclonal antibody therapy AND

                         -  BTKi therapy

               -  Chronic lymphocytic leukemia (CLL)

                    -  CLL with an indication for treatment based on iwCLL guidelines and clinical
                       measurable disease (lymphocytosis > 5×109/L and/or measurable lymph nodes
                       and/or hepatic or splenomegaly)

                    -  Subjects must have received previous treatment as follows:

                         -  Subjects with high-risk features, defined as having complex cytogenetic
                            abnormalities (3 or more chromosomal abnormalities), 17p deletion, TP53
                            mutation, or unmutated IGHV, must have failed at least 1 line of prior
                            therapy, including a BTKi OR

                         -  Subjects with standard-risk features must have failed at least 2 lines
                            of prior therapy, including a BTKi OR

                         -  Subjects who are BTKi intolerant and have received < 6 months of BTKi
                            therapy, must have failed at least 1 high-risk line of non-BTKi therapy
                            or 2 standard-risk lines of non-BTKi therapy OR

                         -  Subjects who are ineligible for BTKi, must have failed at least 1
                            (high-risk) line of non-BTKi therapy or 2 (standard-risk) lines of
                            non-BTKi therapy.

               -  Small lymphocytic lymphoma (SLL)

                    -  SLL (lymphadenopathy) or SLL (splenomegaly and < 5x 109 CD19+ CD5+ clonal B
                       lymphocytes/L [<5000/μL] in the peripheral blood at diagnosis with
                       measurable disease defined as at least one lesion > 1/5 cm in the greatest
                       transverse diameter that is biopsy-proven SLL)

                    -  Subjects must have received previous treatments as follows:

                         -  Subjects with high-risk features, defined as having complex cytogenetic
                            abnormalities (3 or more chromosomal abnormalities), or 17p deletion,
                            or TP53 mutation, or unmutated IGHV, must have failed at least 1 line
                            of prior therapy, including a BTKi OR

                         -  Subjects with standard-risk features must have failed at least 2 lines
                            of prior therapy, including a BTKi OR

                         -  Subjects who are BTKi intolerant and have received < 6 months of BTKi
                            therapy must have failed at least 1 high-risk or 2 standard-risk other
                            lines of non-BTKi therapy OR

                         -  Subjects who are ineligible for BTKi, must have failed at least 1
                            high-risk or 2 standard-risk other lines of non-BTKi therapy.

               -  Mature T cell neoplasms:

                    -  Peripheral T-Cell lymphoma (PTCL)/Cutaneous T-Cell Lymphoma (CTCL)

                    -  R/R after 2 or more prior lines of therapy OR

                    -  Relapse following autologous stem cell transplant OR

               -  T-cell prolymphocytic leukemia (TPLL) --- Diagnosis of TPLL with plan for
                  subsequent therapy.

          -  Evidence of CD37 expression on tumor cells as demonstrated by flow cytometry and/or
             IHC on fresh biopsy or historic samples.

          -  Subjects must have measurable disease according to appropriate disease specific
             criteria.

          -  Adequate absolute lymphocyte count (ALC > 100 cells/ul) within one week of apheresis.

          -  Adequate bone marrow function defined by absolute neutrophil count (ANC) >1000
             cells/mm3 without growth factor support (filgrastim within 7 days of pegfilgrastim
             within 14 days) and untransfused platelet count >50,000 mm3.

          -  Left ventricular ejection fraction > 40%

          -  Adequate hepatic function defined by aspartate aminotransferase (AST) and/or alanine
             aminotransferase (ALT) < 2.5 × upper limit of normal (ULN) and direct bilirubin < 1.5
             × ULN.

          -  Adequate renal function defined by creatinine clearance >30 ml/min using the
             Cockcroft-Gault formula.

          -  The effects of CAR-37 T cells on the developing human fetus are unknown. For this
             reason, women of child-bearing potential and men with partners of childbearing
             potential must agree to use adequate contraception (hormonal or barrier method of
             birth control; abstinence) prior to leukapheresis and until 6 months post CAR-37
             infusion. Should a woman become pregnant or suspect she is pregnant while she or her
             partner is participating in this study, she should inform her treating physician
             immediately. Men with partners of childbearing potential treated or enrolled on this
             protocol must also agree to use adequate contraception prior to the study and until 4
             months after last CAR-37 T cells administration.

          -  Ability and willingness to adhere to the study visit schedule and all protocol
             requirements

        Inclusion criteria for lymphodepletion:

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Karnofsky ≥60%, see
             Appendix A).

          -  No Active, uncontrolled, systemic bacterial, viral, or fungal infection. If febrile,
             the patient must be afebrile for 24 hours and blood cultures negative for 48 hours on
             appropriate antibiotic therapy.

          -  Oxygen saturation >92% on room air while awake.

          -  No additional anti-cancer therapy since leukapheresis excluding steroids at or below
             physiologic dosing.

        Exclusion Criteria:

          -  Prior CD37 targeted therapies.

          -  Treatment with an any investigational cellular therapy within 8 weeks prior to
             apheresis.

          -  Any systemic anti-cancer therapy within 1 weeks of leukapheresis excluding steroids at
             or below physiologic dosing.

          -  Ongoing treatment with chronic immunosuppressants (e.g., cyclosporine or systemic
             steroids above physiologic dosing). Intermittent topical, inhaled, or intranasal
             corticosteroids are allowed.

          -  Ongoing systemic immunosuppression for acute and/or chronic GVH as a result of
             previous allogeneic bone marrow transplant and at least 12 weeks out from prior
             allogeneic SCT.

          -  Significant co-morbid condition or disease which in the judgment of the Principal
             Investigator would place the subject at undue risk or interfere with the study;
             examples include, but are not limited to, cirrhotic liver disease, sepsis, and/or
             recent significant traumatic injury.

          -  Active, uncontrolled, systemic bacterial, viral, or fungal infection.

          -  Subjects with a history of class III or IV congestive heart failure or with a history
             of non- ischemic cardiomyopathy.

          -  Subjects with unstable angina, myocardial infarction, or ventricular arrhythmia
             requiring medication or mechanical control within the previous 3 months.

          -  Subjects with arterial vascular disease such as history of cerebrovascular accident or
             peripheral vascular disease requiring therapeutic anti-coagulation.

          -  Subjects with history of a new pulmonary embolism within 6 months of beginning
             lymphodepletion.

          -  Subjects with second malignancies if the second malignancy has required therapy in the
             last 3 years or is not in complete remission; exceptions to this criterion include
             successfully treated non-metastatic basal cell or squamous cell skin carcinoma, or
             prostate cancer that does not require therapy other than hormonal therapy.

          -  Pregnant or lactating women
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Limiting Toxicity
Time Frame:2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Disease Specific Response
Time Frame:2 years
Safety Issue:
Description:
Measure:Overall Survival
Time Frame:2 years
Safety Issue:
Description:
Measure:Progression Free Survival
Time Frame:2 Years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Marcela V. Maus, M.D.,Ph.D.

Trial Keywords

  • Leukemia
  • Hematologic Malignancy
  • Lymphoma
  • CAR-T

Last Updated

October 22, 2019