Clinical Trial Information

Schema A041703

Protocol: Alliance – A041703

Please Note: Below is a brief description of eligibility, please contact GHCI Research Department to discuss full eligibility requirements.

Eligibility:

Pre-registration Eligibility Criteria (Step 0)

• Submission of bone marrow aspirate and peripheral blood for MRD analysis is mandatory prior to registration; the bone marrow sample should be from the first aspiration (i.e. first pull). Aspirate needle should be redirected if needed to get first pull bone marrow aspirate. It should be initiated as soon as possible after pre-registration.                                                                                                                       • Lumbar Puncture (Spinal Tap) and Intrathecal Methotrexate:
  o  Patients may receive the Day 1 of Course IA dose of intrathecal (IT) methotrexate during the prior-to-registration lumbar          puncture (or the venous line placement) to avoid a second lumbar puncture. If the dose is administered prior to registration, then  systemic chemotherapy must begin within 7 days of this IT chemotherapy.

Registration Eligibility Criteria (Step 1)

1. Morphologic diagnosis of precursor B-cell acute lymphoblastic leukemia (ALL) based on WHO criteria. Patients with Burkitt lymphoma/leukemia are not eligible.
   CD22-positive disease defined as CD22 expression by ≥ 20% of lymphoblasts by local hematopathology evaluation.
   Philadelphia chromosome/BCR-ABL1-negative ALL by cytogenetics, FISH, and/or PCR. If any test is positive for Philadelphia chromosome/BCR-ABL1, then the patient is ineligible.
   No active central nervous system (CNS) leukemia (i.e. only CNS-1 disease allowed). Active CNS leukemia is defined as morphologic evidence of lymphoblasts in the cerebrospinal fluid (CSF), use of CNS-directed local treatment for active disease within 28 days prior to registration, symptomatic CNS leukemia (i.e. cranial nerve palsies or other significant neurological dysfunction) within the 28 days prior to registration, and/or known asymptomatic parenchymal CNS mass lesions; see below for additional guidance. Prophylactic intrathecal medication alone is not an exclusion.

• Categories of CNS Involvement for CNS Evaluation Prior to Registration:
o CNS 1: CSF has < 5 WBC/μL with cytospin negative for blasts; or ≥ 10 RBC/μL with cytospin negative for blasts.
o CNS 2: CSF has < 5 WBC/μL with cytospin positive for blasts; or ≥ 10 RBC/μL with cytospin positive for blasts; or ≥ 10 RBC /μL, WBC/μL ≥ 5 but less than Steinherz/Bleyer algorithm with cytospin positive for blasts (see below).
o CNS 3: CSF has ≥ 5 WBC/μL with cytospin positive for blasts; or ≥ 10 RBC/μL, ≥ 5 WBC/μL and positive by Steinherz/Bleyer algorithm (see below); or clinical signs of CNS leukemia (such as facial nerve palsy, brain/eye involvement or hypothalamic syndrome).
Steinherz/Bleyer Method of Evaluating Initial Traumatic Lumbar Punctures:
▪ If the patient has leukemia cells in the peripheral blood and the lumbar puncture is traumatic and contains ≥ 5 WBC/μL with blasts, the following algorithm should be used to define CNS disease:
CSF WBC/CSF RBC > 2 x (Blood WBC/Blood RBC count)

Patients with known or suspected testicular involvement by leukemia are allowed provided that the patient receives concomitant scrotal/testicular radiotherapy.
• Unilateral or bilateral testicular enlargement should be assessed by ultrasound or other imaging technique. Biopsy is recommended if clinical findings are equivocal or suggestive of hydrocele or a non-leukemic mass, but further assessments are per treating physician discretion.

2.  ECOG Performance Status: 0-2

Clinical Trial Information

Schema S1712

PROTOCOL: SWOG-S1712

Please Note: Below is a brief description of eligibility, please contact GHCI Research Department to discuss full eligibility requirements.

ELIGIBILITY:

1. Patients must have a diagnosis of chronic phase chronic myeloid leukemia without any history of progression to accelerated or blast phase CML. No new bone marrow aspiration and biopsy is needed to prove diagnosis prior to randomization; however, documentation stating the patient is in chronic phase is required.
2. Patients must have detectable BCR-ABL transcripts measured by RT-PCR at a CLIA-approved laboratory and reported on the International Scale (IS) with a value of > 0.0032% IS and ≤ 1.0% IS within 21 days prior to randomization. The RTPCR assay must have the sensitivity to detect a 4.5 log reduction in BCR-ABL transcripts from 100% IS (must be able to detect (0.0032% IS or lower).
3. Patients must have been on TKI therapy for CML for at least 12 months prior to randomization.
4. Patients must be currently receiving treatment with bosutinib (within the allowable dose range of 200-500 mg daily), nilotinib (within the allowable dose range of 150-400 mg BID or a cumulative daily dose of 300-800 mg), or dasatinib (within the allowable dose range of 40-140 mg daily). They must have received their current TKI for a minimum of 6 months prior to randomization and must be expected to remain on the same TKI for the next 12 months.
5. Patient must not have a history of resistance to any prior TKI drug. If patient has received more than one TKI, the reason for changing treatment must have been intolerance to the prior TKI and the treatment change must have occurred ≥6 months prior to randomization.
6. Patients must not be receiving any other investigational agents.
7. Patients must be ≥ 18 years of age.
8. Prior malignancy is allowed providing it does not require concurrent therapy. Exception: Active hormonal therapy is allowed.

Clinical Trial Information

Schema EA9161

PROTOCOL:  ECOG-EA9161

Please Note: Below is a brief description of eligibility, please contact GHCI Research Department to discuss full eligibility requirements.

ELIGIBILITY:

1. Diagnosis of CLL this includes previous documentation of:
   1. Biopsy-proven small lymphocytic lymphoma OR
   2. Peripheral blood lymphocyte count of greater than 5 x109/L
   3. Immunophenotype consistent with CLL.
   4. Negative FISH analysis for t(11;14)(IgH/CCND1) on peripheral blood or tissue biopsy (e.g. marrow aspirate) or negative
      immunohistochemical stains for cyclin D1 staining on involved tissue biopsy (e.g. marrow aspirate or lymph node biopsy.
2. No prior chemotherapy, BTK inhibitor therapy, venetoclax, small molecule signaling inhibitor, or monoclonal anti-body therapy for
   treatment of CLL or SLL.
3. Has met at least one of the following indications for treatment:
   1. Evidence of progressive marrow failure as manifested by the development of worsening anemia (Hg < 11 g/dl) and/or
      thrombocytopenia (Platelets < 100 x 109 /L)
   2. Symptomatic or progressive lymphadenopathy, splenomegaly, or hepatomegaly.
   3. One or more of the following disease-related symptoms:
      • Weight loss ≥ 10% within the previous 6 months
      • Grade 2 or 3 fatigue attributed to CLL
      • Fevers >100.5oF for 2 weeks without evidence of infection
      • Clinically significant night sweats without evidence of infection.
   4. Progressive lymphocytosis (not due to the effects of corticosteroids) with an increase of >50% over a two-month period
      or an anticipated doubling time of less than six months.
4. Age ≥ 18 years and < 70.
5. ECOG performance status between 0-2.
6. Life expectancy of ≥ 12 months.
7. No deletion of 17p13 on cytogenetic analysis by FISH.
8. No current use of corticosteroids. EXCEPTION: Low doses of steroids (< 10 mg of prednisone or equivalent dose of other steroid) used for treatment of non-hematologic medical condition (e.g. chronic adrenal insufficiency) is permitted.
9. No previous autoimmune complications (e.g. autoimmune hemolytic anemia or immune thrombocytopenia) that have developed since the initial diagnosis of CLL and have required treatment with high dose corticosteroids (e.g. equivalent of >20 mg/day of prednisone),
   monoclonal antibody based therapy, or chemotherapy. Prior use ofcorticosteroids for reasons other than treatment of autoimmune
   complications is allowed.
10. No other active primary malignancy (other than non-melanomatous skin cancer or carcinoma in situ of the cervix) requiring treatment or limiting expected survival to ≤ 2 years.
    1. NOTE: If there is a history of prior malignancy, the patient must not currently be receiving other specific treatment (other
       than hormonal therapy for their cancer).

Clinical Trial Information

Schema A041702

PROTOCOL: Alliance-A041702

Please Note: Below is a brief description of eligibility, please contact GHCI Research Department to discuss full eligibility requirements.

ELIGIBILITY:

1. Patients must have been diagnosed with CLL and have > 5000 B-cells per uL of peripheral blood at any point during the course of their disease.
2. Patients must be diagnosed with CLL in accordance with 2018 IWCLL criteria [28] that includes all of the following:
   1. ≥5×109 B lymphocytes (5000/μL) in the peripheral blood measured by flow cytometry at any point in the course of the disease.
   2. On local morphologic review, the leukemic cells must be small mature lymphocytes, and prolymphocytes must not exceed 55% of the blood lymphocytes.
   3. CLL cells on immunophenotype (performed locally) must reveal a clonal B-cell population, which express the B cell surface markers of CD19 and CD20, as well as the T-cell antigen CD5. Patients with bright surface immunoglobulin expression
      or lack of CD23 expression in >10% of cells must lack t(11;14) translocation by interphase cytogenetics.
3. Patients must be intermediate or high-risk Rai stage CLL.
4. Patients must meet criteria for treatment which includes at least one of the following criteria:
   1. Evidence of marrow failure as manifested by the development or worsening of anemia or thrombocytopenia (not attributable to autoimmune hemolytic anemia or thrombocytopenia).
   2. Massive (≥6 cm below the costal margin), progressive or symptomatic splenomegaly.
   3. Massive nodes (≥10 cm) or progressive or symptomatic lymphadenopathy.
   4. Progressive lymphocytosis with a lymphocyte doubling time < 6 months or an increase of ≥ 50% over a 2 month period.
   5. Autoimmune anemia and/or thrombocytopenia that is poorly responsive to standard therapy.
   6. Symptomatic or functional extranodal involvement (e.g. skin, kidney, lung, spine).
   7. Constitutional symptoms, which include any of the following:
      ▪ Unintentional weight loss of 10% or more within 6 months
      ▪ Significant fatigue
      ▪ Fevers >100.5 degrees F for 2 weeks or more without evidence of
      infection
      ▪ Night sweats ≥1 month without evidence of infection
5. Patients must not have had prior therapy for CLL (except palliative steroids or treatment of autoimmune complications of CLL with rituximab or steroids).
6. Treatment with rituximab and/or high dose corticosteroids for autoimmune complications of CLL must be complete at least 4 weeks prior to enrollment. Palliative steroids must be at a dose not higher than 20 mg/day of prednisone or equivalent corticosteroid at the time of registration.
7. Age ≥ 70 years.
8. ECOG performance status 0-2.

Clinical Trial Information

Schema A041501

PROTOCOL: Alliance-A041501

Please Note: Below is a brief description of eligibility, please contact GHCI Research Department to discuss full eligibility requirements.

ELIGIBILITY:

1. Newly diagnosed patients with CD-22 positive B-cell acute lymphoblastic leukemia are eligible. Patients with Burkitt type ALL are NOT
   eligible.
2. Patients who have BCR-ABL fusion transcript determined by FISH or RT-PCR or t(9;22)(q34;q11) by cytogenetics are not eligible and should be considered for enrollment on studies that incorporate imatinib during induction.
   1. Please note: Patients must also be assessed for CD20 positivity and other markers.
3. No prior therapy for ALL except for limited treatment (≤ 7 days) with corticosteroids or hydroxyurea and a single dose of intrathecal cytarabine. However, patients who are being treated with chronic steroids for other reasons (for example, to treat asthma, autoimmune disorders, lupus, etc.) are eligible.
4. No prior therapy for acute leukemia except emergency therapy (corticosteroids or hydroxyurea) for blast cell crisis, superior vena cava syndrome, or renal failure due to leukemic infiltration of the kidneys. When indicated, leukapheresis or exchange transfusion is recommended to reduce the WBC.
5. Single-dose intrathecal cytarabine is allowed prior to registration or prior to initiation of systematic therapy for patient convenience. This is usually done at the time of the diagnostic bone marrow or venous line placement to avoid a second lumbar puncture. Systemic chemotherapy must begin within 72 hours of this intrathecal therapy.
6. Age ≥ 18 years and < 40 years.
7. ECOG Performance Status 0-2.