Immune System Cells for the Treatment of Relapse or Refractory Hematological Cancers

Inclusion Criteria

• Patients with hematological malignancies with an expression of CD70 in the pre-enrollment tumor sample >= 10% measured by immunohistochemistry or flow cytometry.
• Patients must meet diseases specific eligibility criteria.
• Patients at least 3 weeks from last cytotoxic chemotherapy at the time of starting lymphodepleting chemotherapy, except for hydroxyurea which is allowed for peripheral blood count control in acute myeloid leukemia (AML) patients until the day prior to administration of lymphodepleting chemotherapy. Patients may continue tyrosine kinase inhibitors or other targeted therapies until up to three days prior to administration of lymphodepleting chemotherapy.
• Localized radiotherapy to one or more disease sites is allowed prior the infusion provided that there are additional disease sites that are not irradiated to assess response.
• Karnofsky performance scale > 50% for patients who are >16 years old or Lansky score ≥ 50% for patients who are ≤ 16 years of age.
• Serum creatinine =< 2.0x upper limit of normal (ULN) and estimated glomerular filtration rate (eGFR using the chronic kidney disease-epidemiology collaboration [CKD-EPI] equation) >= 30 ml/min/1.73 m^2.
• Alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) =< 3 x ULN or =< 5 x ULN if documented liver metastases.
• Total bilirubin < 2x ULN, except in subjects with Gilbert’s syndrome in whom total bilirubin must be =< 3x ULN. No history of liver cirrhosis. No ascites.
• Cardiac ejection fraction >= 40%, no clinically significant pericardial effusion as determined by an echocardiography (ECHO), and no uncontrolled arrhythmias or symptomatic cardiac disease.
• No clinically significant, pleural effusion (per principal investigator [PI] discretion), baseline oxygen saturation > 92% on room air and adequate pulmonary function with forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and diffusion capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin [Hgb]) > 50%.
• Able to provide written informed consent.
• 12-80 years of age.
• Weight >= 40 kg.
• All participants who are able to have children must practice effective birth control while on study and up to 3 months post completion of study therapy. Acceptable forms of birth control for female patients include: hormonal birth control, intrauterine device, diaphragm with spermicide, condom with spermicide, or abstinence, for the length of the study. If the participant is a female and becomes pregnant or suspects pregnancy, she must immediately notify her doctor. If the participant becomes pregnant during this study, she will be taken off this study. Men who are able to have children must use effective birth control while on the study. If the male participant fathers a child or suspects that he has fathered a child while on the study, he must immediately notify his doctor.
• Signed consent to long-term follow-up protocol PA17-0483 to fulfill the institutional responsibilities to various regulatory agencies.
• Are willing and able to provide informed consent, as appropriate (either directly or through a legally authorized representative [LAR]).
• Multiple myeloma (MM): * Patients with relapsed or refractory MM (patients with solitary plasmacytoma are not eligible) who meet the following criteria: ** Have received at least three previous lines of therapy including an immunomodulatory imide drug (IMiD), a proteasome inhibitor, and an anti-CD38 antibody with or without autologous stem cell transplant (SCT). ** Have measurable disease (serum monoclonal (M) protein level >= 0.5 g/dL, and/or urine M protein level >= 200 mg/day, and/or involved serum free light chain (FLC) level >= 10 mg/dL provided the serum-free light-chain ratio is abnormal. * Patients with relapsed or refractory plasma cell leukemia who have received at least two previous regimens.
• B-cell non-Hodgkin’s lymphoma: * Patients with a history of B-cell non-Hodgkin’s lymphoma defined as: diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma, follicular lymphoma, marginal zone lymphoma, mantle cell lymphoma and high grade transformation of follicular, marginal zone lymphoma or Richter’s transformation of chronic lymphocytic leukemia who have received at least 2 lines of standard chemoimmunotherapy or targeted therapy and have persistent disease. * Patients with a history of B-cell non-Hodgkin’s lymphoma defined above with relapsed disease following two or more lines of standard therapy or an autologous or allogeneic stem cell transplant.
• Hodgkin’s lymphoma: * Patients with a history of Hodgkin’s lymphoma who have received at least 2 lines of standard chemoimmunotherapy or targeted therapy and still have persistent disease. * Patients with a history of Hodgkin’s lymphoma with relapsed disease following two or more lines of standard therapy or an autologous or allogeneic stem cell transplant and have active disease.
• T-cell non-Hodgkin’s lymphoma: * Patients with history of T acute lymphoblastic leukemia (T-ALL) or T-cell non Hodgkin’s lymphoma defined as T cell lymphoblastic lymphoma (T-LBL) peripheral T-cell lymphoma (PTCL-not otherwise specified [NOS], Sezary syndrome [SS], mycosis fungoides [MF] >= stage IIB, hepatosplenic gamma/delta T cell non-Hodgkin lymphoma [NHL], leukemic and lymphomatous subtypes of angioimmunoblastic T-cell lymphoma [AITL], anaplastic large cell lymphoma [ALCL], subcutaneous panniculitis-like T-cell lymphoma [SPTCL], enteropathy-associated T-cell lymphoma [EATL]) who have received at least 2 lines of standard systemic chemo-immunotherapy or targeted therapy and have persistent disease. * Patients with history of T-lymphoid malignancies as defined above with relapsed disease following standard therapy or a stem cell transplant.
• Acute myeloid leukemia (AML): * Patients with active (> 5% of blasts or positive minimal residual disease (MRD) at a level of > 0.1% measured by multiparameter flow cytometry) relapsed or refractory acute myeloblastic leukemia. Who have received at least two lines of therapy. One or more of the lines of therapy must include hypomethylating agents and venetoclax. Patients who have mutations for which there are Food and Drug Administration (FDA) approved targeted therapies (i.e. FLT3) must also have received at least one of such agent. Patients with diagnosis of acute promyelocytic leukemia are not eligible. ** Relapsed AML is defined as patients who had a first complete remission (CR) before developing recurrent disease. ** Refractory AML is defined as patients that have not achieved a CR after 2 cycles of standard induction chemotherapy. * For patients with secondary AML (AML evolving from myelodysplastic syndrome [MDS] or myeloproliferative disorder [MPD]) the therapies received prior transformation will be considered when determining the eligibility of the patient. For example, patients who received hypomethylating agents for the treatment of the MDS are not required to receive again hypomethylating agents to treat the secondary AML to be eligible. Similarly, patients who received two lines of therapy for the management of the MDS or MPD are not required to receive an additional two lines of therapy for the management of the AML to be eligible.
• Myelodysplastic syndrome: * Patients with high risk or intermediate risk myelodysplastic syndrome (MDS) who have received at least two lines of therapy and have positive MRD at a level of > 0.1% measured by multiparameter flow cytometry or are not in morphological remission. * Patients with relapse high risk or intermediate risk MD after at least 2 lines of therapy. Relapse is defined as positive MRD at a level of > 0.1% measured by multiparameter flow cytometry or loss of morphological remission.
• Blastic transformation of chronic myeloid leukemia: * Patients with myeloblastic or lymphoblastic transformation of chronic myeloid leukemia with detectable disease at MMR level or higher after one line of therapy intended to treat the blastic transformation. * Blastic transformation is defined as >= 20% of blasts in peripheral blood or bone marrow.
• Germ cell tumors: * Male and female patients with germ cell tumors (both seminoma and nonseminoma) who have failed either 2 or more lines of cisplatin-based chemotherapy or high- dose chemotherapy with autologous stem-cell transplant rescue.

Exclusion Criteria

• Positive beta human chorionic gonadotropin (HCG) in female of child-bearing potential defined as not postmenopausal for 24 months or no previous surgical sterilization or lactating females.
• Presence of clinically significant grade 3 or greater toxicity from the previous treatment, as determined by PI.
• Presence of uncontrolled fungal, bacterial, viral, or other infection not responding to appropriate therapy.
• Known active hepatitis B or C.
• Known HIV with detectable viral load.
• Presence of active neurological disorder(s).
• Active autoimmune disease within 12 months of enrollment.
• Amyloidosis or POEMS syndrome.
• Active cerebral or meningeal involvement by the malignancy.
• Active (defined as requiring therapy) acute or chronic graft versus host disease (GVHD).
• Any other malignancy known to be active, except for treated cervical intraepithelial neoplasia and non-melanoma skin cancer.
• Presence of any other serious medical condition that may endanger the patient at investigator discretion.
• Major surgery <4 weeks prior to first dose of the preparatory chemotherapy.
• Allogeneic SCT or donor lymphocyte infusion (DLI) < 12 weeks prior to first dose of preparatory chemotherapy.
• Concomitant use of other investigational agents.
• Concomitant use of other anti-cancer agents.
• Patients receiving systemic steroid therapy at time of enrollment (physiological substitutive doses are allowed), or have received antithymocyte globulin or lymphocyte immune globulin within 14 days of enrollment or alemtuzumab within 28 days of enrollment.
• Patients receiving immunosuppressive therapy.