Must have achieved an objective response (CR/PR) or stable disease (SD) upon completion of scheduled treatment
Patients must have achieved a CR or CRi
Patients who have achieved a CR or CRi must have maintained peripheral blood evidence of a CR or CRi
CRITERIA FOR MAINTENANCE THERAPY-STEP 4: Patients must have maintained peripheral blood evidence of a remission and must have a CR or CRi, confirmed on restaging BM aspirate and biopsy
Patients must be registered to Step 2 within 28 days after count recovery; (Note: there is no maximum allotted time period for count recovery, providing patient remains in CR or CRi)
Patients must have achieved a response to induction chemotherapy (either CR or PR by Cheson 2007 criteria) and be without known progression
leukemia in 1st relapse with initial CR duration < 6 months,
Calculated Cr Cl >= 30 ml/min; eligible for reduced dose methotrexate
The subjects should be in first or second CR (including CR and SCR) or PR (including PR and VGPR)
Achieved at least a partial response (PR) to therapy
Acute lymphoblastic leukemia (B- or T-acute lymphoblastic leukemia [ALL])\r\n* Complete response (CR)1-ultra high risk features\r\n** Unfavorable cytogenetics\r\n** Hypodiploidy\r\n** Induction failure\r\n** Minimal residual disease (MRD) positive after consolidation\r\n* CR2\r\n** Any of the high risk features listed in CR1\r\n** B-ALL: any relapse considered eligible for transplant \r\n** T-ALL\r\n* CR 3-any
Participant has confirmed, morphologically documented AML in CR1. For the purposes of registration, CR1 will be defined as < 5% blasts in the BM with no morphologic characteristics of acute leukemia (e.g., Auer Rods) in the BM with no evidence of extramedullary disease such as central nervous system involvement or granulocytic sarcoma.
Participants with CR with incomplete count recovery (CRp or CRi) are allowed. Incomplete platelet recovery (CRp) is defined as CR with platelet count < 100 x 109/L. Incomplete blood count recovery (CRi) is defined as CR with residual neutropenia < 1 x 109/L with or without complete platelet recovery. Red blood cell count (RBC) and platelet transfusion independence is not required.
The maximum time allowed from establishment of CR1 to registration is 12 months.
Participant has confirmed ongoing morphologically documented AML in CR1. For the purposes of randomization, CR1 will be defined as < 5% blasts with no morphologic characteristics of acute leukemia (e.g., Auer Rods) in the BM with no evidence of extramedullary disease such as central nervous system involvement or granulocytic sarcoma.
Patients must have received pre-study nivolumab for up to 12 months and have 2 consecutive tumor assessments confirming Complete response (CR), Partial response (PR), or Stable disease (SD)
Documented major response [partial response (PR), very good partial response (VGPR), complete response (CR)] according to the International Myeloma Working Group (IMWG) uniform response criteria, version 2011, after this initial therapy.
Patients must have received at least one prior therapy for CLL or NHL, need additional treatment (or have need for cytoreduction as mentioned above), and meet criteria for relapsed or refractory disease; they may not be a candidate for curative therapy; relapsed disease is defined as a patient who previously achieved a complete remission (CR) or a partial remission (PR), but after a period of six or more months demonstrates evidence of disease progression; refractory disease is defined as progression within six months of the last anti-leukemic or anti-lymphoma therapy, or any response less than a CR or PR
Patients with HD with 4th or greater CR, PR, and/or SD are ineligible.
Creatinine (Cr) > 1.5 mg/dL or Cr clearance < 60 mL/m^2
Patients with B-lineage ALL in CR2 and beyond with molecular failure at any time point after 2 months of salvage therapy are allowed
On treatment with ruxolitinib for at least 3 months and have been on a stable dose for at least 8 weeks and have not achieved a complete response (CR) by International Working Group (IWG) criteria
Patients must have received treatment on PBTC-029 or PBTC-029B for a minimum of 12 courses with at least stable disease, or had a sustained response (partial response [PR]/ complete response [CR]) but remained on treatment < 12 courses
Absence of a documented partial response (PR) or complete response (CR) according to RECIST 1.1 or CA 125 response by Gynecologic Cancer Intergroup (GCIG) criteria to neoadjuvant chemotherapy
Disease response noted (i.e. CR, non-CR, or not applicable): assessed as per disease specific criteria
Diagnosis of one of the following: a): Patients >= 60 years of age with previously untreated Ph-positive ALL [either t(9;22) and/or BCR-ABL positive] (includes patients initiated on first course of therapy before cytogenetics known): This patient could have received one or two courses of chemotherapy with or without other tyrosine kinase inhibitors (TKIs) and still eligible; b) If they achieved CR, they are assessable only for event-free and overall survival; or c) If they failed to achieve CR, they are assessable for CR, event-free, and overall survival; d) Patients >= 18 years of age with relapsed/refractory Ph-positive ALL.
Previous tumor response to PD-1 or PD-L1 inhibiting therapy\r\n* Note: Tumor response is defined as complete response (CR), partial response (PR), or stable disease (SD) that is durable for at least 16 weeks
Patients with complete response (CR)/very good partial response (VGPR) disease
Patients >= 60 years of age with previously treated Ph-positive ALL, after 1-2 courses of chemotherapy with or without other tyrosine kinase inhibitors (TKIs). If they achieved CR, they are assessable only for event-free and overall survival, or If they failed to achieve CR, they are assessable for CR, event-free, and overall survival.
For stage I/II patients treated with primary chemotherapy-radiation, they must have failed (no CR or progression after CR) at least one salvage combination chemotherapy treatment regimen
Chemo-sensitive (defined by complete response [CR] or partial response [PR] to most recent chemo regimen) based on pre-transplant positron emission tomography (PET) within 6 weeks of autologous transplant
Achieved either partial or CR to the bendamustine regimen of at least 12 months in duration before relapse/progression.
Patients must be in first CR/VGPR
Patients must have: a. Relapsed and/or refractory non-APL AML that has failed to achieve a complete remission (CR) or partial remission (PR) following standard induction therapy, or has relapsed after any duration of CR or PR i. Patients must have measurable disease with bone marrow blasts ?5%at screening b. Relapsed and/or refractory higher-risk MDS (High / Very High Risk, as defined by the Revised International Prognostic Scoring System (IPSS-R)) that has failed to achieve a CR or PR, or any hematologic improvement (HI, per IWG 2006 criteria) after standard therapy with hypomethylating agents (e.g., azacitidine, decitabine), or has relapsed after any duration of CR or PR or HI i. Patients must have measurable disease with bone marrow blasts >5% at screening c. Newly diagnosed, treatment-naïve non-APL AML in patients who, at the time of study entry are unlikely to tolerate standard intensive chemotherapy due to age, performance status, or comorbidities based on at least one of the following criteria (Ferrara et al, 2013): i. Age ? 75 years old ii. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 3 iii. Cardiac history of congestive heart failure (CHF) or documented ejection fraction (EF) ? 50% iv. Pulmonary disease with DLCO ? 65% or FEVI ? 65% v. Creatinine clearance ? 30 mL/min to < 45 mL/min vi. Hepatic impairment with total bilirubin > 1.5 to ? 3.0 x upper limit of normal (ULN) vii. Any other comorbidity that the Investigator judges to be incompatible with intensive chemotherapy, and reviewed and approved by the Sponsor prior to enrollment d. Transfusion dependent lower-risk MDS without the del 5q abnormality, in patients refractory to erythropoietin treatment or unlikely to respond to erythropoietin treatment (EPO >500). i. Lower-risk MDS: Very Low /Low / Intermediate Risk, as defined by IPSS-R. ii.Red blood cell (RBC) transfusion dependent anemia defined as no eight consecutive weeks without RBC transfusions within the 16 weeks prior to study entry, or ?4 RBC transfusions within the 8 weeks prior to study entry. iii.Refractory to or ineligible for ESAs is defined as RBC-Transfusion Dependence despite ESA treatment of ?40,000 units/week recombinant human erythropoietin for 8 weeks or an equivalent dose of darbepoetin (150 µg/week) or serum EPO level >500 mU/mL in patients not previously treated with ESAs.
Acute lymphoblastic leukemia (ALL)/lymphoma: second or greater CR; CR1 unable to tolerate consolidation chemotherapy due to chemotherapy-related toxicities; CR1 high-risk ALL; high risk ALL is defined as having one of the following:\r\n* Evidence of high risk cytogenetics, e.g. t(9;22), t(1;19), t(4;11), other MLL rearrangements, IKZF1\r\n* Recipient age 30 years and older at diagnosis\r\n* White blood cell counts of greater than 30,000/mcL (B-ALL) or greater than 100,000/mcL (T-ALL) at diagnosis\r\n* Central nervous system (CNS) leukemia involvement during the course of disease \r\n* Slow cytologic response (> 10% lymphoblasts in bone marrow on day 14 of induction therapy)\r\n* Evidence of persistent immunophenotypic or molecular minimal residual disease (MRD) at the end of induction and consolidation therapy
Participants who have had a complete response (CR) after pre-study therapy are not eligible for study
Patients with complete response (CR) or stringent CR after induction therapy as defined by International Response Criteria after most recent therapy
Patients with B-lineage ALL in a) hematologic complete remission (CR) beyond CR1 at time of transplant; patients beyond CR1 or with primary induction failure may be without minimal residual disease, b) any residual disease defined by positive flow > 0.01%, detection of breakpoint cluster region-abelson murine leukemia viral oncogene homolog 1 (BCR-ABL) transcript by polymerase chain reaction (PCR) with a sensitivity of 1/10,000, or detection of the t(9;22) translocation in any metaphases by cytogenetics at time of transplant, or presence of the MLL gene
Achieving partial response (PR) or very good partial response (VGPR) with systemic chemotherapy
Patients who achieved complete response (CR) prior to autologous HCT
Continued CR, CRp, or CRi within 3 weeks of first dose WT-1 specific CD8+ T cells
Relapse after minimal residual disease (MRD)-negative CR within 3 months of most recent GCLAM chemotherapy
Acute lymphoblastic leukemia (ALL)/lymphoma: second or greater CR; CR1 unable to tolerate consolidation chemotherapy due to chemotherapy-related toxicities; CR1 high-risk ALL; high risk ALL is defined as having one of the following:\r\n* Evidence of high risk cytogenetics, e.g. t(9;22), t(1;19), t(4;11), other MLL rearrangements, IKZF1\r\n* 30 years of age or older at diagnosis\r\n* White blood cell counts of greater than 30,000/mcL (B cell [B]-ALL) or greater than 100,000/mcL (T cell [T]-ALL) at diagnosis\r\n* Central nervous system (CNS) leukemia involvement during the course of disease\r\n* Slow cytologic response (> 10% lymphoblasts in bone marrow on day 14 of induction therapy)\r\n* Evidence of persistent immunophenotypic or molecular minimal residual disease (MRD) at the end of induction and consolidation therapy
Presence of measurable or evaluable disease (unless patient has achieved a complete response (CR) following first-line antineoplastic therapy).
Patients without measurable or evaluable disease (unless patients achieved a complete response (CR) following 1st-line antineoplastic therapy).
Acute myeloid leukemia: High risk first complete remission (CR1) (as evidenced by preceding myelodysplasia [MDS], high risk cytogenetics, >= 2 cycles to obtain CR, erythroblastic or megakaryocytic leukemia, FLT-3 ITD +; second or higher complete response [CR2+]); all patients must be in CR as defined by hematological recovery, AND < 5% blasts by light microscopy within the bone marrow with a cellularity of >= 15%
Acute lymphocytic leukemia (ALL): Factor that define high risk CR1 include but are not limited to cytogenetics demonstrating t(9;22), t (1:19), t(4;11), other MLL rearrangements, hypodiploidy, or IKZF1 abnormalities), DNA index < 0.81, > 1 cycle to obtain CR or presence minimal residual disease (MRD); patients in CR2+ are eligible; all patients must be in CR as defined by hematological recovery, AND < 5% blasts by light microscopy within the bone marrow with a cellularity of >=15%
Patients with complete response (CR)/very good partial response (VGPR) disease
Patients must have a sustained clinical response (PR, nodular PR [nPR], complete clinical response [CCR], CR with incomplete marrow recovery [CRi], CR) with documented residual disease (>= 1 CLL cell per 10,000 leukocytes or >= 0.01% MRD) either in the blood, bone marrow or a lymph node >= 3.5 cm by any available techniques
Relapsed or refractory B-cell ALL:\r\n* 1st or greater bone marrow (BM) relapse OR\r\n* Any marrow relapse after allogeneic hematopoietic stem cell transplantation (HSCT) and > 100 days from transplant OR\r\n* For patients with refractory disease:\r\n** < 60 years old that have not achieved a complete remission (CR) after > 2 or more chemotherapy regimens\r\n** >= 60 years old that have not achieved a CR after 1 prior chemotherapy regimen
Participants who received at least only one line of previous therapy and achieved either complete response (CR) or partial response (PR) for at least 24 weeks (from the last day of the last cycle) after their first line of therapy, but are not eligible for high dose chemotherapy with autologous stem cell transplantation (HD-ASCT)
Patients with AML in remission (defined as CR, CR with incomplete platelet recovery –CRp-, CR with incomplete hematologic recovery -CRi-, or partial remission defined as a bone marrow with < 10% blasts after therapy with or without hematologic recovery)
Creatinine (Cr) < 2.0
Acute lymphoblastic leukemia (ALL)\r\n* High-risk CR1 including:\r\n* Poor-risk cytogenetics (e.g., Philadelphia chromosome t(9;22) or 11q23 rearrangements)\r\n* Presence of minimal disease by flow cytometry after 2 or more cycles of chemotherapy\r\n* No complete remission (CR) within 4 weeks of initial treatment\r\n* Induction failure\r\n* CR2 or CR3 with either\r\n** =< 10% blasts in the marrow or \r\n** =< 5% blasts in the peripheral blood
Creatinine measurement (Cr) < 1.7
Relapsed or refractory B-cell acute lymphoblastic leukemia (ALL)\r\n* 1st or greater bone marrow (BM) relapse OR\r\n* Any marrow relapse after allogeneic hematopoietic stem cell transplant (HSCT) and > 100 days from transplant OR\r\n* For patients with refractory disease:\r\n** < 60 years old that have not achieved a CR after >= 2 or more chemotherapy regimens\r\n** >= 60 years old that have not achieved a CR after 1 prior chemotherapy regimen\r\n** Patients with Philadelphia chromosome positive (Ph+) ALL are eligible if they have failed tyrosine kinase inhibitor therapy
Patients who had anything less than a CR (PR, SD or progressive disease) to their last salvage regimen
Hodgkin lymphoma that is: \r\n* PIF (primary induction failure): did not enter complete remission with first line of therapy; Note: a patient with PIF who responds to salvage therapy with a PR or CR is also eligible (and would be considered PIF-sensitive)\r\n* Early 1st relapse: initial CR of > 3 months and < 12 months after 1st line chemotherapy\r\n* 1st relapsed HL in a patient who is not in CR after 2 cycles of salvage therapy\r\n* In 2nd or subsequent relapse (RL) whether in CR or not after salvage therapy
Creatinine (Cr) < 2.0
Diagnosis of one of the following:\r\n* Previously untreated Ph-positive ALL (either t[9;22] and/or bcr-abl positive) (includes patients initiated on first course of hyper-CVAD before cytogenetics known)\r\n* Previously treated Ph-positive ALL, after 1-2 courses of chemotherapy with or without other tyrosine kinase inhibitors (TKIs)\r\n** If they achieved complete response (CR), they are assessable only for event-free and overall survival, or\r\n** If they failed to achieve CR, they are assessable for CR, event-free, and overall survival
Other acute leukemias that are ambiguous lineage or of other types e.g. blastic plasmacytoid dendritic cell neoplasm in CR1 or CR2
Poor Prognosis Non-Seminomas Germ Cell Tumor in >= partial response (PR)1/complete response (CR)1 or Good or Intermediate Prognosis Seminomas and Non-Seminomas Germ Cell Tumor in >= PR1 or >= CR2 as defined by the International Germ Cell Cancer Consensus Classification; Patients with increasing tumor markers only (i.e., no imaging evidence of progressive disease) are eligible for transplant
Acute myeloid leukemia: high risk first complete remission (CR)1 as evidenced by: \r\n* High risk cytogenetics; t(4;11) or other mixed lineage leukemia (MLL) rearrangements; chromosome 5, 7, or 19 abnormalities; complex karyotype (> 5 distinct changes)\r\n* >= 2 cycles to obtain complete remission (CR)\r\n*Second CR (CR2) or higher preceding myelodysplasia (MDS)\r\n* All patients must be in CR or early relapse (i.e., < 15% blasts in bone marrow [BM])
Acute lymphocytic leukemia: high risk CR1 as evidenced by: \r\n* High-risk cytogenetics: t(4;11) or other MLL rearrangements; hypodiploid; t(9;22)\r\n* > 1 cycle to obtain CR\r\n* CR2 or higher\r\n* All patients must be in CR as defined by hematological recovery, AND < 5% blasts by light microscopy within the bone marrow with a cellularity of >= 15%
Patients must be receiving a v-raf murine sarcoma viral oncogene homolog B1 (B-RAF) inhibitor and failed to achieve PR or CR or have progressive disease in response to B-RAF treatment (Cohort C)
Achieves PR or CR in response to B-RAF treatment (Cohort C)
Acute myeloid leukemia (AML): high risk complete response (CR)1 (as evidenced by preceding myelodysplastic syndromes [MDS], high risk cytogenetics, >= 2 cycles to obtain CR, erythroblastic or megakaryocytic leukemia; CR2+; all patients must be in CR as defined by hematological recovery, AND < 5% blasts by light microscopy within the bone marrow with a cellularity of >=15%
Acute lymphocytic leukemia (ALL): high risk CR1 as defined by cytogentics (such as t(9;22), t (1:19), t(4;11), other mixed lineage leukemia (MLL) rearrangements, hypodiploidy, or IKZF1 abnormalities), deoxyribonucleic acid (DNA) index < 0.81, > 1 cycle to obtain CR or presence minimal residual disease (MRD); patients in CR2+ are eligible; all patients must be in CR as defined by hematological recovery, AND < 5% blasts by light microscopy within the bone marrow with a cellularity of >= 15%
Acute myeloid leukemia: high risk first complete remission (CR1) (as evidenced by preceding myelodysplastic syndrome [MDS], high risk cytogenetics such as those associated with MDS or complex karyotype, > 2 cycles to obtain complete response [CR] or erythroblastic and megakaryocytic); second or greater CR
Acute lymphoblastic leukemia/lymphoma: high risk CR1 as evidenced by high risk cytogenetics (e.g. t(9;22), t(1;19),t(4;11), other mixed-lineage leukemia (MLL) rearrangements, hypodiploidy or IKAROS family zinc finger 1 [IKZF1]), > 1 cycle to obtain CR or evidence of minimal residual disease (MRD); patients in second or greater CR are also eligible
Have achieved a response (partial response (PR) or better) to at least 1 prior therapy.
Acute lymphoblastic leukemia (ALL)/lymphoma: second or greater CR; CR1 unable to tolerate consolidation chemotherapy due to chemotherapy-related toxicities; CR1 high-risk ALL; high risk ALL is defined as having one of the following:\r\n* Evidence of high risk cytogenetics, e.g. t(9;22), t(1;19), t(4;11), other MLL rearrangements, IKZF1\r\n* 30 years of age or older at diagnosis\r\n* White blood cell counts of greater than 30,000/mcL (B-cell [B]-ALL) or greater than 100,000/mcL (T-cell [T]-ALL) at diagnosis\r\n* CNS leukemia involvement during the course of disease\r\n* Slow cytologic response (> 10% lymphoblasts in bone marrow on day 14 of induction therapy)\r\n* Evidence of persistent immunophenotypic or molecular minimal residual disease (MRD) at the end of induction and consolidation therapy
>=6 months after completing any line of chemotherapy, or after autologous stem cell transplantation, and having attained either a very good partial response (VGPR) or a complete response (CR), and without the need for haematological maintenance therapies Inclusion Criteria for Group 3
Confirmed free light chain complete response (CR) during the first three cycles of first-line chemotherapy where at least the first cycle has been with cyclophosphamide, bortezomib, dexamethasone (CyBorD).
Creatinine (Cr) =< 1.5 x ULN
105 For DLBCL: Refractory (no prior CR/CMR) to first or later line of treatment or relapsed (prior CR/CMR) after two or more prior treatments., with at least one treatment consisting of standard multiagent chemotherapy containing an anthracycline AND an approved anti-CD20 agent. Examples of appropriate therapy include but are not limited to R-CHOP (14 or 21), R-CHOEP, and DA-REOCH. For FL: Refractory (no prior CR/CMR) to first or later line of treatment or relapsed (prior CR/CMR) after two or more prior treatments, with at least one treatment consisting of a standard chemotherapy containing an approved anti-CD20 agent. Examples of appropriate therapy include but are not limited to R-CHOP, R-CVP, and BR. For MCL: Refractory (no prior CR/CMR) to first or later line of treatment or relapsed (prior CR/CMR) after two or more prior treatments, with at least one treatment consisting of a standard chemotherapy containing an approved anti-CD20 agent. Examples of appropriate therapy include but are not limited to R-CHOP, BR and hyper-CVAD alternating with R-MTX/Ara-C. For subjects with refractory B-NHL and who have received radiotherapy, PET positivity should be demonstrated no less than 6 weeks after the last dose of radiotherapy
COHORT 2: patients with high risk disease having undergone an allogeneic hematopoietic stem cell transplant from a 10/10 human leukocyte antigen (HLA) matched donor with one of the following disease subtypes:\r\n* Acute myeloid leukemia (AML) in CR1 with high risk features (European Leukemia Network [ELN]) at presentation\r\n** Diagnostic sample with either t(6;9), t(9;22), 11q23, inv 3, -5, -7, del17p, complex cytogenetics, NPMwt-flt3ITD+, OR p53 mutation (mut); patients whose samples have mutations in RUNX1 or ASXL1 are also eligible (unless the patient has favorable cytogenetics)\r\n* AML in CR1 with measurable minimal residual disease (MRD) by molecular (e.g., myeloid mutation profile, polymerase chain reaction [PCR] for NPM1, core-binding factor [CBF], mixed lineage leukemia [MLL]) or flow cytometry \r\n* AML not in CR1 (including patients with morphologic CR but with incomplete recovery, CRi)\r\n* Myelodysplastic syndrome (MDS) with complex cytogenetics, 17p deletion or p53 mutation, or JAK2 or RAS mutation\r\n* Treatment-related MDS or AML\r\n* Acute lymphoblastic leukemia (ALL) not in CR1\r\n* ALL with MRD\r\n* Any hematologic malignancy relapsed or with persistent disease after allogeneic hematopoietic stem cell transplant\r\n* Multiple myeloma\r\n* Non-Hodgkin lymphoma (NHL) with chemoresistant disease at time of transplant\r\n* Any patient undergoing allogeneic hematopoietic stem cell transplant and an anticipated rate of relapse > 80% based upon published data and for which there is consensus amongst the Hematologic Malignancies Tumor Study Group that enrollment is appropriate
Must have achieved CR/CRi with less than 2 induction regimens that contain cytarabine and anthracycline
Patients with: A) diffuse large B-cell lymphoma (DLBCL) with one of the following: A.1) primary refractory (no CR to 1st line), A.2) high-risk relapse (CR1 < 6 months (mo), secondary International Prognostic Index [IPI] >1, high lactate dehydrogenase [LDH]), A.3) refractory relapse: no response to >= 1 salvage line and not eligible to receive other novel salvage therapies, such as chimeric antigen receptor T-cells (CAR-T) in a timely fashion or have already failed these; B) Hodgkin’s with one of the following: B.1) primary refractory (no CR or progressive disease [PD] within 3 months), B.2) high-risk relapse (CR1 < 1 year, extranodal relapse, B symptoms), B.3) refractory relapse: no response to >= 1 salvage line C) T-non Hodgkin's lymphoma (T-NHL) with one of the following: C.1) primary refractory (no CR to 1st line), C.2) high-risk relapse (within 6 months), C.3) refractory relapse to >= 1 line of salvage. D) any other lymphoma that is refractory or relapsed and that does not qualify for autologous transplant protocols of higher priority.
Any curable cancer with a complete response (CR) of > 2 years duration.
Patients must have achieved a CR or CRi (or morphologic leukemia-free state for those patients proceeding to Arm G transplant)
Patients who have achieved a CR or CRi must have maintained peripheral blood evidence of a CR or CRi
Pediatric patients must have a hematological malignancy as described below:\r\n* AML: high risk CR1 (preceding MDS, intermediate to high risk cytogenetics, >= 2 cycles to obtain CR, French-American-British classification system [FAB] M6); CR2+, first relapse with < 25% blasts in bone marrow; morphologic complete remission with incomplete blood count recovery; therapy-related AML for which prior malignancy has been in remission for at least 12 months\r\n* ALL: high risk CR1 (Philadelphia chromosome positive [Ph+] ALL, MLL rearrangements with slow early response, hypodiploidy, end of induction M3 bone marrow, end of induction M2 with M2-3 at day 42, evidence of minimal residual disease [MRD]); high risk CR2 (Ph+ALL, bone marrow relapse < 36 months from induction, T-lineage relapse at any time, very early isolated central nervous system (CNS) relapse, slow induction after relapse at any time, evidence of MRD); >= CR3\r\n* NK cell lymphoblastic leukemia in any CR\r\n* Biphenotypic or undifferentiated leukemia in any CR or if in first relapse must have less than 25% blasts in bone marrow\r\n* Myelodysplastic syndrome (MDS) at any stage\r\n* Chronic myelogenous leukemia (CML) in chronic or accelerated phase\r\nEvidence of CNS leukemia must be treated and in CNS CR to be eligible for the study
Subjects with a prior diagnosis of AML (excluding acute promyelocytic leukemia) based on World Health Organization classification who did not achieve complete response (CR) with their previous therapy or who have relapsed after achieving a complete response (CR) are eligible; any number of relapses will be eligible
Patients must be within 2 years of achieving CR following chemotherapy
Creatinine [Cr] < 2.0
Diffuse large B-cell lymphoma\r\n* All patients will be eligible in >= second complete remission (CR2) or >= first partial response (PR1)\r\n* Patients with a high intermediate or high International Protein Index (IPI) (>= 2 for age-adjusted IPI or >= 3 for IPI) at diagnosis will be eligible in first CR
For stage I/II patients treated with primary radiation, they must have failed (no CR or progression after CR) at least one salvage combination chemotherapy treatment regimen
Acute myelogenous leukemia\r\n* CR #1 and “high-risk” (excludes t[8;21], t[15;17], or inv[16])\r\n* CR #2 or greater
Acute lymphocytic leukemia\r\n* CR #1 + “high-risk” (t[9;22] or bcr-abl+; t[4;11], 1[1;19], t[8;14])\r\n* In CR #2 or greater
Subject must have achieved a CR/CRi/CRp (criteria as defined by [Cheson et al, 2003], see Section 5.3) with first line treatment and has hematologic relapse.
Achieved a response of stable disease, partial response, or complete response following the last cycle of frontline treatment. In addition, patients must have relapsed less than or equal to 6 months from the completion of frontline therapy at the time of initial dosing in this clinical trial.
Patient must have clinical complete response or partial response following completion of chemotherapy course.
Patients with life-threatening acute leukemia (high-risk ALL in 1st CR, ALL in 2nd CR, high-risk AML in 1st CR, AML in 2nd CR.) or myelodysplastic syndromes. Morphological CR must be documented and minimal residual disease measurement before transplantation is recommended.
Refractory as defined by not achieving a CR after 2 cycles of a standard chemotherapy regimen chemotherapy regimen or chemorefractory as defined by not achieving a CR after 1 cycle of standard chemotherapy for relapse leukemia OR
Consolidation and/or maintenance (including SCT) may have been given in CR/CRi, but are not counted as a line of treatment.
Consolidation and/or maintenance (including SCT) may have been given in CR/CRi, but are not counted as a line of treatment.
Primary refractory as defined by not achieving a CR after 2 cycles of a standard chemotherapy regimen or chemorefractory as defined by not achieving a CR after 1 cycle of standard chemotherapy for relapsed leukemia OR.
Have achieved CR/CRi following therapy with hypomethylating agents
History of a non-CLL malignancy except for adequately treated in situ, stage 1 or 2 carcinoma in Complete Response (CR), or any other cancer that has been in CR for >=2 years after end of cancer treatment.
Relapsed patients must have achieved a complete remission (CR) or CR with incomplete blood count recovery (CRi) lasting < 6 months with their last induction regimen
Patients must have achieved CR; patients who achieved only CRi or PR, and patients who relapse from CR before this registration are not eligible
Creatinine ? 1.5 x ULN or Cr Cl > 60 cc/min
Received at least four treatments with MK-3475 beyond the date when the initial complete response (CR) was declared
Any curable cancer with a complete response (CR) of > 5 years duration.
Subjects treated with prior ipilimumab must have had partial response (PR), complete response (CR), or at least 6 months of stable disease followed by disease progression.
Subjects with metastatic breast cancer who have achieved stable disease (SD), partial response (PR), or complete response (CR) after at least 1 regimen of anticancer therapy (i.e. chemotherapy or target therapy, either alone or in any combination). Involvement of supraclavicular lymph node is considered metastasis.
Concurrent systemic cancer therapy (hormones, biologics or chemotherapy) can be continued if distant metastases are non-responsive (i.e. no complete response [CR] or partial response [PR]) on that regimen for >= 8 weeks as assessed by the investigator
CR, partial response (PR) or stable disease (SD) after Step 1
Patients with complete response (CR)/very good partial response (VGPR) disease
Histologically or cytologically confirmed extensive-stage disease small cell lung cancer (ED SCLC) with ongoing clinical benefit (stable disease [SD], partial response [PR], or complete response [CR]) following completion of 4 cycles of first-line platinum-based therapy
Chronic Lymphocytic Leukemia (CLL) in CR if RIC is to be used; in CR or partial response (PR) if FIC is to be used
Chemotherapy-sensitive lymphoma in status other than 1st CR
For arms A and B, participants must have relapsed after or been refractory to first-line chemotherapy, i.e., they must have failed to achieve CR after first-line therapy or must have relapsed subsequently if they achieved CR; for arm C, participants will be eligible if transplant is performed as consolidation of first remission (partial or complete)
Be actively receiving duvelisib monotherapy on the previous study (within 14 days of study entry) and demonstrating clinical benefit (complete response [CR]/ partial response [PR]/ stable disease [SD]) of continued use, or
Documented response to ASCT (PR, VGPR, CR/stringent complete response [sCR]) according to IMWG criteria.
Creatinine (Cr) < 3
Early first relapse (< 36 months from original diagnosis) after achieving a CR (B-ALL) or first relapse any time following the original diagnosis after achieving a CR (T-ALL)
A very good partial response (VGPR) or better after induction therapy with/without consolidative high-dose therapy/autologous stem cell transplantation (HDT/ASCT).\r\n* Very good partial response (VGPR): \r\n** Serum and urine M-component detectable by immunofixation but not on electrophoresis or\r\n** >= 90% or greater reduction in serum M-component plus urine M-component < 100 mg per 24 hours (h)\r\n* Complete response (CR):\r\n** Negative immunofixation of serum and urine and\r\n** Disappearance of any soft tissue plasmacytomas and\r\n** < 5% plasma cells in bone marrow\r\n* Stringent complete response (sCR)\r\n** CR as defined above plus\r\n** Normal free light chain ratio and\r\n** Absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence\r\n* MRD positive by flow cytometry
receiving ibrutinib for at least 6 months with a response less than complete response/remission (CR) and have high-risk features as defined in inclusion criterion 5a
During dose escalation, patients must have received at least one prior therapy, need additional cytoreduction, and meet criteria for relapsed or refractory disease; relapsed disease is defined as a patient who previously achieved a CR or a PR, but after a period of six or more months demonstrates evidence of disease progression; refractory disease is defined as progression within six months of the last anti-leukemic therapy, or any response less than a CR or PR; patients who are previously untreated, and do not wish to receive chemotherapy or immunotherapy, are eligible for the dose expansion portion of the study
Subjects must have entered the Maintenance Phase and are under ongoing maintenance treatment or subjects who stopped maintenance treatment because of a complete response (CR) or subjects with an initial partial response (PR) or CR or at least 3 months of stable disease (SD) on tumor assessment and who subsequently have a confirmed and documented disease progression (per immune-related Response Evaluation Criteria in Solid Tumors [RECIST] criteria)
Enrolled in University Of Minnesota study MT2001-10 “Allogeneic Bone Marrow Transplantation Using Less Intensive Therapy” and fitting into one of the following disease categories:\r\n* Acute myelogenous leukemia - high risk first complete remission (CR1) (as evidenced by preceding myelodysplastic syndrome [MDS], intermediate to high risk cytogenetics, >= 2 cycles to obtain complete remission (CR), erythroblastic or megakaryocytic leukemia; second complete remission (CR2)+; all patients must be in CR as defined by hematological recovery (absolute neutrophil count [ANC] > 0.5 x 10^9/L), AND < 5% blasts by light microscopy within the bone marrow with a cellularity of >= 15%\r\n* Acute lymphocytic leukemia - high risk CR1 [t(9;22), t (1:19), t(4;11) or other mixed-lineage leukemia [MLL] rearrangements] or > 1 cycle to obtain CR; CR2+; all patients must be in CR as defined by hematological recovery (ANC > 0.5 x 10^9/L), AND < 5% blasts by light microscopy within the bone marrow with a cellularity of >= 15%\r\n* Chronic myelogenous leukemia all types except blast crisis (note treated blast crisis in chronic phase is eligible)\r\n* Non-Hodgkin lymphoma or Hodgkin’s lymphoma demonstrating chemosensitive disease\r\n* Myelodysplastic syndrome with severe pancytopenia, leading to either transfusion dependency or increased risk for infections
Cohorts 1 and 3: Participants must have stable disease or be responders (partial response [PR] or complete response [CR]) to neratinib in the CNS at the time of non-CNS progression
CLL patients with evidence of residual disease, who have achieved partial response (PR), nodular partial response (nPR) or complete response (CR) with detectable minimal residual disease (MRD) following upfront therapy consisting of pentostatin, cyclophosphamide and rituximab\r\n* The presence of MRD will be assessed by the flow cytometry and polymerase chain reaction at the Memorial Sloan Kettering Cancer Center (MSKCC) Diagnostic Molecular Pathology Laboratory
Acute lymphocytic leukemia\r\n* Adult: (>= 22 years) >= second complete remission (CR2) OR first CR (CR1) with a high risk feature:\r\n** Matched sibling donor for recipient treated on adult leukemia regimen\r\n** t(9:22) or breakpoint cluster region (bcr)-Abelson (abl)+; t(4:11), t(1:19), t(8:14), 11q23 (mixed lineage leukemia [MLL] rearrangements) complex cytogenetics (5 or more chromosomal abnormalities), hypodiploidy (< 44 chromosomes.; note that patients with acute lymphoblastic leukemia (ALL) blast crisis who emerge from chronic myelogenous leukemia (CML) are also eligible\r\n** Primary induction failure, defined as failure to achieve CR with primary induction chemotherapy\r\n** High white blood cell (WBC) (> 30,000 for B-cell ALL and > 100,000 for T-cell ALL) at diagnosis\r\n** Persistence of minimal residual disease despite induction chemotherapy\r\n* Pediatric (< 22 years): >= CR2 OR CR1 with high risk features\r\n** Matched sibling donor for recipient treated on adult leukemia regimen\r\n** Primary induction failure (M3 [> 25% with greater 200 cells counted] marrow at day 29), M2 (5-25% blasts with greater than 200 cells counted) bone marrow or minimal residual disease (MRD) > 1% at day 29 who then fail at day 43 with either M2 or M3 bone marrow (BM) or MRD > 1%\r\n** Persistent leukemia and t(9;22) (MRD > 1% day 29 or MRD > 0.01% end-consolidation)\r\n** 11q23 (MLL) rearrangements detected by cytogenetic or polymerase chain reaction (PCR) at initial diagnosis who are slow early responders (M2/M3 at day 14 or MRD > 0.01% at day 29)\r\n** Extreme hypodiploidy (< 44 chromosomes or deoxyribonucleic acid [DNA] index of < 0.81) detected by cytogenetic/ploidy analysis
Best response achieved was ?Partial Response (PR)
Prior bendamustine treatment within 1 year of randomization not resulting in a CR or PR for at least 6 months
Patients must have B-ALL refractory, relapsed, minimal residual disease (MRD), or in first complete remission (CR) as described below\r\n* Complete remission is defined as restoration of normal hematopoiesis with a neutrophil count > 1,000 x 10^6/L, a platelet count > 100,000 x 10^6/L, and hemoglobin > 10 g/dL; blasts should be < 5% in a post-treatment bone marrow differential; furthermore, there should be no clinical evidence of leukemia for a minimum of four weeks\r\n* MRD is defined as patients meeting the criteria for CR above, but with residual disease measured by a quantitative polymerase chain reaction (qPCR), or by flow, or by deep-sequencing of the immunoglobulin heavy chain (IgH) rearrangements; the assay from blood and/or bone marrow defines MRD by qPCR as a cycle threshold (CT) that is at least 1 CT value < than the lowest CT value from the background; outside laboratory tests may suffice for this assessment at the discretion of the principal investigator\r\n* Relapsed B-ALL will be defined as patients that meet the above criteria for a CR before developing recurrent disease (increased bone marrow blasts); refractory patients will be defined as patients that have not achieved a CR after 1 cycle of induction chemotherapy
Patients who have stable (SD) or responding disease (PR or CR) documented by the appropriate radiological, clinical, or laboratory assessments within 12 weeks before enrollment (Note: response criteria from the previous AG-013736 protocol should be used to determine stable or responding disease).
Mantle cell NHL must be beyond first complete response (CR)
Must have achieved a minimum response of partial response (PR, nPR, CRi, CR, and MRD-negative CR) (IWCLL guidelines for the diagnosis and treatment of chronic lymphocytic leukemia [Hallek, 2008]) following completion of second-line induction therapy prior to randomization (documentation of response status must be available). Second-line induction therapy must be documented to have been of sufficient duration.
Diagnosis of one of the following: Previously untreated Ph-positive ALL [either t(9;22) and/or bcr-abl positive] (includes patients initiated on first course of hyper-CVAD before cytogenetics known) These groups will be analyzed separately. After 1-2 courses of chemotherapy with or without imatinib mesylate (Gleevec) · If they achieved CR, they are assessable only for event-free and overall survival, or · If they failed to achieve CR, they are assessable for CR, event-free, and overall survival. Patients with relapsed Ph-positive ALL or lymphoid blast phase of CML.
Creatinine (Cr) =< 2.0
Refractory B-ALL, defined by not having achieved a CR or CRi after two attempts at remission induction using standard regimens, or
Patient has achieved CR or partial response (PR) per per investigator's assessment following completion of CHOP-based therapy and has had radiological assessment within 21 days prior to randomization.
ALCL (ALK+) with IPI score less than 2 at initial diagnosis and CR after CHOP-based therapy
No evidence of progressive disease following completion of first-line chemotherapy (i.e., ongoing CR, PR, or SD per RECIST v1.1 guidelines )
Must be within 75 days of completion of first-line treatment regimen; must have achieved complete response (CR/unconfirmed complete response [CRu]) to first-line treatment
If CSF was positive for lymphoma cells at diagnosis or during first-line treatment and/or a slit lamp examination was positive at diagnosis or during first-line treatment, then the CSF and vitreal studies must have been repeated and must have indicated CR; Note: CR requires complete disappearance of all enhancing abnormalities on gadolinium-enhanced MRI; if CSF was positive for lymphoma cells at diagnosis or during first-line treatment and/or slit lamp examination was positive at diagnosis or during first-line treatment, then the CSF and vitreal studies must have been repeated and must have indicated CR; for CRu, some patients will have a small but persistent enhancing abnormality on MRI related to biopsy or focal hemorrhage; it is often difficult to ascertain whether this represents a residual nidus of tumor or scar tissue; if the abnormality does not change or slowly involutes without therapy and corticosteroids, it is reasonable to categorize as a CRu; at the time CR/CRu is determined, the patient should not have used corticosteroids for at least two weeks
Multiple myeloma\r\n* No prior auto hematopoietic transplantation (HCT) fitting into one of the following categories:\r\n** Early disease stage (first complete response [CR1]/first partial response [PR1]) with high-risk molecular features:\r\n*** By FISH or cytogenetics:\r\n**** t(4;14)\r\n**** t(14;16) \r\n**** t(14;20)\r\n**** -17 or -17p\r\n**** -1p or +1q\r\n*** By cytogenetics:\r\n**** -13 or -13q\r\n*** By gene expression profile (GEP):\r\n**** High risk GEP\r\n** Early disease stage (CR1/PR1) with high-risk clinical features:\r\n*** Plasma cell leukemia at presentation\r\n*** Poor count recovery after chemotherapy, making collections from autologous HCT unlikely to be adequate\r\n** Late disease stage (CR2/second partial response [PR2+]) with high- risk clinical features\r\n*** Minimal (< 50% reduction of serum M protein or free light chains, or if non-secretory, < 50% reduction in marrow plasma cell burden) response or progression after therapy with at least two novel agents, including lenalidomide and bortezomib, who demonstrates chemosensitivity to any other salvage regimen\r\n*** Poor count recovery after chemotherapy, making collections for autologous HCT unlikely to be adequate
Relapsed or refractory AML, defined as either: recurrence of disease after a complete remission (CR), or failure to achieve CR with initial therapy.
Part specific requirements: eligible to receive induction; achieved CR/CRi with standard induction and eligible to receive consolidation; in CR with documented blood count recovery for maintenance
Any curable cancer with a complete response (CR) of > 5 years duration.
Creatinine (Cr) > 2.5
Patients with a complete response (CR) to their previous regimen must have a cancer antigen (CA)-125 within normal range; this criterion is not applicable to patients who enroll with a partial response (PR) to their previous regimen
The patient has achieved a first or second CR or CRi. For patients without evidence of MRD in CR/CRi, CR (or CRi) must have been initially identified within 12 months prior to screening. OR The patient has achieved first or second CR or CRi with evidence of MRD as determined locally at least 6 months post stem cell transplant without evidence of acute or chronic graft-versus-host disease post-transplant and has not received immunosuppressant therapy for at least 14 days prior to SL-401 therapy.
Completed and recovered from all planned induction and consolidation therapy according to the institution's standard of care, and achieved a complete remission (CR)/CR with incomplete platelet recovery (CRp); either first or second CR.
Subjects who have received prior bendamustine are eligible if they achieved a response (CR/PR) which lasted > 6 months after the end of bendamustine containing treatment.
Cr ? 2X ULN
Cr ?2X the ULN
The patient is in complete remission (i.e. CR1, CR2, …):
Patients with: diffuse large B-cell lymphoma (DLBCL) with one of the following:\r\n* Primary refractory (no complete response [CR] to 1st line); \r\n* High-risk relapse (CR1 < 6 months, secondary international prognostic index [IPI] > 1 or high lactate dehydrogenase [LDH]); or, \r\n* Refractory relapse: no response (stable disease [SD] or progressive disease [PD]) to >= 1 line of salvage
Hodgkin’s with one of the following: \r\n* Primary refractory (no CR to 1st line or PD within 3 months);\r\n* High-risk relapse (CR1 < 1 year, extranodal relapse or B symptoms); or, \r\n* Refractory relapse: no response (SD or PD) to >= 1 line of salvage
Willingness to participate in CR program
Patient must have had a complete response (CR)/partial response (PR)/stable disease (SD), 4-6 weeks after completing last fraction of radiation therapy
Patients with acute undifferentiated, biphenotypic, or bilineal leukemia, which is in 1st or greater complete remission (CR) or partial remission (PR):\r\n* Cr will be defined as an M1 marrow (< 5% blasts), no evidence of extramedullary disease, and an absolute neutrophil count >= 1.0 x 10^9/L; cases where the ANC is < 1.0 x 10^9/L and rising will also be considered; the PI will need to approve such cases for enrollment; CR without platelet recovery (CRp) will be considered complete remissions); PR will be defined as an M2 marrow (5-19% blasts), no evidence of extramedullary disease, and an absolute neutrophil count >= 1.0 x 10^9/L); cases where the ANC is < 1.0 x 10^9/L and rising will also be considered; the PI will need to approve such cases for enrollment\r\n* Chronic myelogenous leukemia (CML):\r\n** Chronic phase with resistance to tyrosine kinase inhibitors\r\n** Accelerated phase (development of cytogenetic abnormality in addition to t(9:22), blood blast percentage >= 10, blood basophil percentage >= 20, platelet count < 100,000 X 10^9/L)\r\n** Blast crisis\r\n** 2nd or greater chronic phase\r\n* Acute Lymphoblastic Lymphoma in 2nd or greater complete remission:\r\n** Complete remission includes confirmed complete response (CR) defined as the disappearance of all evidence of disease from all sites for at least 4 weeks; bone marrow and cerebrospinal fluid (CSF) must be normal and any macroscopic nodules in any organs detectable on imaging techniques shall no longer be present; imaging should include positron emission tomography (PET) scanning; CR will also include unconfirmed complete responses defined as a residual lymph node mass > 1.5 cm in greatest transverse diameter that has regressed by > 75% in sum of the products of the greatest perpendicular diameters (SPD), or any residual lesions in organs that have decreased by > 75%, with a negative PET scan, negative bone marrow and CSF\r\n* Peripheral T cell lymphoma (PTCL):\r\n** In first response (must have at least a partial response)\r\n*** PTCL, unspecified\r\n*** Hepatosplenic gamma-delta T cell lymphoma\r\n** Recurrent PTCL (must be treatment sensitive with at least a partial response); if patient has had a previous autologous transplant, the melphalan and fludarabine conditioning regimen must be utilized\r\n** Chronic myelomonocytic leukemia\r\n** Atypical (breakpoint cluster region- abelson murine leukemia viral oncogene homolog 1 [BCR-ABL] negative) chronic myelogenous leukemia\r\n** Hodgkin lymphoma that has recurred or progressed after an autologous BMT\r\n*** Newly diagnosed or recurrent disease initially refractory to intensive chemotherapy; a partial response or better must be achieved prior to transplantation; eligibility of newly diagnosed cases must be discussed with the study principal investigator (PI)\r\n*** Disease that has recurred or progressed after an autologous BMT; salvage chemotherapy must produce a partial response or better; the melphalan and fludarabine conditioning-regimen must be used for these patients\r\n** Non-Hodgkin lymphoma other than lymphoblastic or peripheral T cell lymphoma\r\n*** Newly diagnosed or recurrent disease initially refractory to intensive chemotherapy; a partial response or better must be achieved prior to transplantation; eligibility of newly diagnosed cases must be discussed with the study PI\r\n*** Disease that has recurred or progressed after an autologous BMT; salvage chemotherapy must produce at least a partial response; the melphalan and fludarabine conditioning-regimen must be used for these patients
Spot urine Ca:Cr ratio >0.25 (>250 mg/g creatinine)
(Part B only) Histologically confirmed DLBCL/MCL/FL/PTCL/MF/CLL on the basis of excisional lymph node or extranodal tissue biopsy; diagnosis of relapsed/refractory disease defined as 1) recurrence of disease after a Complete Response (CR), or 2) Partial Response (PR), Stable Disease (SD) at completion of treatment regimen preceding entry into study, subjects must not be candidates for standard therapy, subjects who have not received Stem Cell Translplant (SCT) must be ineligible to receive SCT.
Patient must be scheduled to undergo stem cell transplantation for one of the following diagnoses: \r\n* Acute myeloid leukemia (AML) in first complete remission (CR1) (first complete remission, CR or CR with incomplete blood count recovery [CRi]) or second complete remission (CR2) (second complete remission, CR or CRi) \r\n* Acute lymphoblastic leukemia (ALL) in CR1 or CR2, (CR or CRi)\r\n* Myelodysplastic syndrome (MDS) without progression to AML \r\n* Chronic myelogenous leukemia (CML)\r\n* Non-Hodgkin’s lymphoma (NHL) or Hodgkin’s disease (HD)\r\n* Chronic lymphocytic leukemia (CLL)\r\n* Multiple myeloma (MM)
Patients with benign hematologic disorders such as severe aplastic anemia do not have disease response requirements; patients with a malignant hematologic disorder must be in complete response (CR) (MRD is allowed) with the exception of the following:\r\n* Patients with MDS/MPN only require < 5% myeloblasts on bone marrow evaluation\r\n* Patients with AML or ALL may be in complete remission with incomplete marrow recovery (CRi), patients with MM may be in very good partial response (VGPR)
Multiple myeloma in CR/very good partial response (VGPR)
Prior or ongoing response (IWG 2006: HI, PR, CR, or marrow CR) to treatment with azacitidine for injection or decitabine, at any time in the subject's prior history, which includes relapsed disease
Creatinine (Cr) > 2.0
Creatinine (Cr) =< 1.5
Subject has confirmed morphologically documented AML, excluding acute promyelocytic leukemia (APL), in CR1 (including CRp and CRi). For the purposes of enrollment, CR will be defined as < 5% blasts in the bone marrow with no morphologic characteristics of acute leukemia (e.g., Auer rods) in the bone marrow with no evidence of extramedullary disease such as central nervous system involvement or granulocytic sarcoma.
Has relapsed (disease progression after most recent therapy) or refractory (failure to achieve Complete Response [CR] or Partial Response [PR] to most recent therapy) classical Hodgkin Lymphoma.