Combination Chemotherapy and Donor Stem Cell Transplant in Treating Patients With Aplastic Anemia or Hematologic Cancer

NCT00003816 | Completed Phase 2 Results DMC

• 1 other identifier: RP 98-15
• Study Type: interventional
• Target: 361
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Giving chemotherapy drugs and total-body irradiation before a donor stem cell helps stop the growth of cancer or abnormal cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. It is not yet known which combination chemotherapy regimen is most effective when given before a donor stem cell transplant in treating aplastic anemia or hematologic cancer. PURPOSE: This phase II/III trial is studying different combination chemotherapy regimens to compare how well they work when given before donor stem cell transplant in treating patients with aplastic anemia or hematologic cancer.

Conditions

Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases; Nonmalignant Neoplasm; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific

Keywords

recurrent childhood acute lymphoblastic leukemia; recurrent cutaneous T-cell non-Hodgkin lymphoma; Burkitt lymphoma; Waldenstrom macroglobulinemia; recurrent childhood lymphoblastic lymphoma; recurrent childhood acute myeloid leukemia; recurrent adult acute myeloid leukemia; recurrent adult acute lymphoblastic leukemia; relapsing chronic myelogenous leukemia; refractory chronic lymphocytic leukemia; chronic phase chronic myelogenous leukemia; accelerated phase chronic myelogenous leukemia; blastic phase chronic myelogenous leukemia; adult acute myeloid leukemia in remission; adult acute lymphoblastic leukemia in remission; childhood acute myeloid leukemia in remission; childhood acute lymphoblastic leukemia in remission; polycythemia vera; essential thrombocythemia; refractory anemia; refractory anemia with excess blasts; refractory anemia with excess blasts in transformation; chronic myelomonocytic leukemia; T-cell large granular lymphocyte leukemia; acute undifferentiated leukemia; recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma; recurrent adult diffuse small cleaved cell lymphoma; recurrent adult diffuse mixed cell lymphoma; recurrent adult diffuse large cell lymphoma; recurrent adult immunoblastic large cell lymphoma; recurrent adult lymphoblastic lymphoma; recurrent adult Burkitt lymphoma; recurrent adult T-cell leukemia/lymphoma; secondary acute myeloid leukemia; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; prolymphocytic leukemia; intraocular lymphoma; recurrent childhood small noncleaved cell lymphoma; recurrent childhood large cell lymphoma; recurrent mantle cell lymphoma; angioimmunoblastic T-cell lymphoma; anaplastic large cell lymphoma; recurrent mycosis fungoides/Sezary syndrome; primary myelofibrosis; childhood chronic myelogenous leukemia; atypical chronic myeloid leukemia; myelodysplastic/myeloproliferative disease, unclassifiable; recurrent marginal zone lymphoma; recurrent small lymphocytic lymphoma; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; splenic marginal zone lymphoma; adult acute myeloid leukemia with t(8;21)(q22;q22); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with t(15;17)(q22;q12); childhood myelodysplastic syndromes; aplastic anemia; unspecified adult solid tumor, protocol specific; unspecified childhood solid tumor, protocol specific

Outcome Measures

Primary Outcomes (1)

• CR Rate

  Rate of Complete Remission by Day +100

  day 100

Secondary Outcomes (3)

• Toxicity/TRM at Day 100

  Day +100

• 4 Year PFS

  4 years

• 4 yr OS

  4-year

Study Arms (9)

Regimen 1

EXPERIMENTAL

Patients receive busulfan IV over 2 hours every 6 hours on days -7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2.

Drug: busulfan; Drug: cyclophosphamide

Regimen 2

EXPERIMENTAL

Patients receive cyclophosphamide IV over 2 hours on days -5 to -2 and anti-thymocyte globulin IV over 4-8 hours on days -5 to -3.

Biological: anti-thymocyte globulin; Drug: cyclophosphamide

Regimen 3

EXPERIMENTAL

Patients receive cyclophosphamide IV over 2 hours on days -5 and -4 and total-body irradiation (TBI) twice daily on days -3 to -1.

Drug: cyclophosphamide; Radiation: total-body irradiation

Regimen 4

EXPERIMENTAL

Patients receive fludarabine IV over 30 minutes on days -6 to -2 and melphalan IV over 1 hour on days -3 and -2.

Drug: fludarabine phosphate; Drug: melphalan

Regimen 5

EXPERIMENTAL

Patients receive etoposide IV over 26 hours beginning on day -5, cyclophosphamide IV over 2 hours on day -4, and TBI twice daily on days -3 to -1.

Drug: cyclophosphamide; Drug: etoposide; Radiation: total-body irradiation

Regimen 6

EXPERIMENTAL

Patients receive cyclophosphamide IV over 24 hours, carboplatin IV over 24 hours, and thiotepa IV over 24 hours on days -7 to -4.

Drug: carboplatin; Drug: cyclophosphamide; Drug: thiotepa

Regimen 7

EXPERIMENTAL

Patients receive fludarabine IV over 30 minutes on days -5 to -1 and anti-thymocyte globulin IV over 4-8 hours on days -5 to -2.

Biological: anti-thymocyte globulin; Drug: fludarabine phosphate

Regimen 8

EXPERIMENTAL

Patients receive cyclophosphamide IV over 2 hours on days -5 and -4, TBI twice daily on days -3 to -1, and anti-thymocyte globulin IV over 4-8 hours on days -3 to -1.

Biological: anti-thymocyte globulin; Drug: cyclophosphamide; Radiation: total-body irradiation

Regimen 9

EXPERIMENTAL

Patients receive busulfan IV over 2 hours every 6 hours and anti-thymocyte globulin IV over 4-8 hours on days -7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2.

Biological: anti-thymocyte globulin; Drug: busulfan; Drug: cyclophosphamide

Interventions

anti-thymocyte globulin BIOLOGICAL

Given IV

Regimen 2; Regimen 7; Regimen 8; Regimen 9

busulfan DRUG

Given IV

Regimen 1; Regimen 9

carboplatin DRUG

Given IV

Regimen 6

cyclophosphamide DRUG

Given IV

Regimen 1; Regimen 2; Regimen 3; Regimen 5; Regimen 6; Regimen 8; Regimen 9

etoposide DRUG

Given IV

Regimen 5

fludarabine phosphate DRUG

Given IV

Regimen 4; Regimen 7

melphalan DRUG

Given IV

Regimen 4

thiotepa DRUG

Given IV

Regimen 6

total-body irradiation RADIATION

Given twice daily for 3 days

Regimen 3; Regimen 5; Regimen 8

Eligibility Criteria

• Age: 4 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Diagnosis of one of the following: * Severe aplastic anemia as defined by either of the following: * Marrow cellularity (\< 25% \[or 25-50% cellularity with \< 30% of remaining cells hematopoietic in origin\]) * At least 2 of the following abnormal peripheral blood counts: * Reticulocyte count \< 1% (corrected for hematocrit) * Platelet count \< 20,000/mm\^3 * Neutrophil count \< 500/mm\^3 * Histologically confirmed hematologic malignancy, including any of the following: * Acute leukemia * Resistant or recurrent disease after combination chemotherapy with at least one standard regimen OR in first remission and at high risk of relapse * Acute myeloid leukemia (AML) (antecedent myelodysplastic syndromes \[MDS\], secondary AML, or high-risk cytogenetic abnormalities) * Acute lymphoblastic leukemia (ALL) (high-risk cytogenetic abnormalities) * Chronic myeloid leukemia (CML) * Chronic phase, accelerated phase, or blast phase * Myeloproliferative disorders or MDS, including any of the following: * Myelofibrosis * Polycythemia vera\* * Essential thrombocythemia\* * Refractory anemia * Refractory anemia with excess blasts * Refractory anemia with excess blasts in transformation * Chronic myelomonocytic leukemia NOTE: \* Only if transformed to AML or MDS * Lymphoproliferative disease * Recurrent or persistent, symptomatic disease after first-line chemotherapy, including any of the following: * Chronic lymphocytic leukemia (CLL) (≥ 20% marrow involvement) * Waldenstrom macroglobulinemia * Low-grade non-Hodgkin lymphoma * Intermediate or high-grade non-Hodgkin lymphoma, meeting 1 of the following criteria: * Resistant or recurrent disease after combination chemotherapy with one standard regimen * Lymphoblastic lymphoma or small noncleaved cell lymphoma in first remission and at high risk of relapse * CNS disease * Bone marrow disease and LDH greater than 300 * Solid tumor that would otherwise be treated on RPCI-DS-9115 (or equivalent autologous stem transplant protocol) AND has a syngeneic donor * Autologous bone marrow transplant not possible (or desirable) due to 1 of the following: * History of marrow tumor * Inadequate marrow dose * Abnormal marrow histology or function prior to storage * Thrombocytopenia or leukopenia * Marrow cellularity \< 20% * Histocompatible donor identified * Well-matched donor, as defined by 1 of the following: * Family member matched for 5 or 6 HLA specificities (A, B, DR)\* * Unrelated donor meeting compatibility criteria of the National Marrow Donor Program (matched for HLA A, B, and DRB1 antigens)\* * Identical twin sibling * If a compatible cord blood donor is identified and there is no suitable unrelated donor available, patient may receive cord blood transplant NOTE: \*Patients ≤ 25 years of age may be singly mismatched at the A or B loci NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology. PATIENT CHARACTERISTICS: Age: * 4 to 70 Performance status: * Zubrod 0-2 OR * Karnofsky 70-100% Life expectancy: * Not specified Hematopoietic: * See Disease Characteristics Hepatic: * Bilirubin \< 3 times normal (unless due to disease) * Alkaline phosphatase \< 3 times normal (unless due to disease) * SGOT \< 3 times normal (unless due to disease) * Hepatitis B surface antigen negative * No severe hepatic disease that would preclude study participation Renal: * Creatinine normal * Creatinine clearance ≥ 50 mL/min * No severe renal disease that would preclude study participation Cardiovascular: * Cardiac ventricular ejection fraction ≥ 50% by MUGA or echocardiogram * No uncontrolled or severe cardiovascular disease (e.g., myocardial infarction, congestive heart failure, symptomatic angina, life threatening arrhythmia, or hypertension within the past 6 months) Pulmonary: * DLCO or DLVA ≥ 50% predicted (corrected for hemoglobin or alveolar ventilation) Other: * No serious concurrent medical or psychiatric illness * No other serious organ dysfunction (unless due to underlying disease), including the following: * Uncontrolled bacterial, viral, or fungal infection * Uncontrolled peptic ulcer disease * Uncontrolled diabetes mellitus * HIV negative * Cytomegalovirus status known * Not pregnant PRIOR CONCURRENT THERAPY: Biologic therapy: * Not specified Chemotherapy: * See Disease Characteristics * Pretransplant cytoreductive chemotherapy allowed for patients with relapsed or refractory disease Endocrine therapy: * Not specified Radiotherapy: * Not eligible for total-body irradiation if prior radiotherapy exceeded the following limits: * Mediastinum: 3,600 cGy * Heart: 3,600 cGy * Whole lungs: 1,200 cGy * Small bowel: 3,600 cGy * Kidneys: 1,200 cGy * Whole liver: 1,600 cGy * Cranial spinal: 3,600 cGy * Brain: 4,000 cGy * Retina: 4,000 cGy Surgery: * Not specified

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263-0001, United States

Location

MeSH Terms

Conditions

Myeloproliferative Disorders; Leukemia; Lymphoma; Myelodysplastic Syndromes; Myelodysplastic-Myeloproliferative Diseases; Neoplasms; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, T-Cell, Cutaneous; Burkitt Lymphoma; Waldenstrom Macroglobulinemia; Leukemia, Myeloid, Acute; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myeloid, Chronic-Phase; Leukemia, Myeloid, Accelerated Phase; Blast Crisis; Polycythemia Vera; Thrombocythemia, Essential; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts; Leukemia, Myelomonocytic, Chronic; Leukemia, Large Granular Lymphocytic; Leukemia, Biphenotypic, Acute; Lymphoma, Follicular; Lymphoma, Non-Hodgkin; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Large-Cell, Immunoblastic; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Prolymphocytic; Intraocular Lymphoma; Dendritic Cell Sarcoma, Interdigitating; Lymphoma, Mantle-Cell; Immunoblastic Lymphadenopathy; Lymphoma, Large-Cell, Anaplastic; Mycosis Fungoides; Sezary Syndrome; Primary Myelofibrosis; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Lymphoma, B-Cell, Marginal Zone; Congenital Abnormalities; Anemia, Aplastic

Interventions

Antilymphocyte Serum; Busulfan; Carboplatin; Cyclophosphamide; Etoposide; fludarabine phosphate; Melphalan; Thiotepa; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Lymphoid; Lymphoma, T-Cell; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Leukemia, Myeloid; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Blood Coagulation Disorders; Thrombocytosis; Blood Platelet Disorders; Anemia; Leukemia, T-Cell; Eye Neoplasms; Histiocytic Disorders, Malignant; Histiocytosis; Lymphadenopathy; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Bone Marrow Failure Disorders

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Coordination Complexes; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Radiotherapy; Therapeutics; Investigative Techniques

Results Point of Contact

• Title: Theresa Hahn, PhD
• Organization: Roswell Park Comprehensive Cancer Center

theresa.hahn@roswellpark.org

716-845-5819

Study Officials

• Philip L. McCarthy, MD

  Roswell Park Cancer Institute

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 1999
• First Posted: January 27, 2003
• Study Start: October 19, 1998
• Primary Completion: July 12, 2019
• Study Completion: July 12, 2019
• Last Updated: August 13, 2021
• Results First Posted: August 13, 2021

Record last verified: 2021-07

Locations

US (1)