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Phase 3 N=361 Treatment

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

Chronic Myeloproliferative Disorders · Leukemia · Lymphoma · Myelodysplastic Syndromes · Myelodysplastic/Myeloproliferative Diseases

Enrolled (actual)
361
Serious AEs
25.8%
Results posted
Aug 2021
Primary outcome: Primary: CR Rate — 42; 55; 134; 18 Participants

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
anti-thymocyte globulin (Biological); busulfan (Drug); carboplatin (Drug); cyclophosphamide (Drug); etoposide (Drug); fludarabine phosphate (Drug); melphalan (Drug); thiotepa (Drug); total-body irradiation (Radiation)
Age
Pediatric, Adult, Older Adult · 4+ yrs
Sex
All
Sponsor
Roswell Park Cancer Institute
Primary completion
Jul 2019

Outcome Measures

OutcomeResultp-value
PRIMARY
CR Rate
42; 55; 134; 18; 7
SECONDARY
Toxicity/TRM at Day 100
3; 4; 31; 4; 4
SECONDARY
4 Year PFS
49.1; 52.2; 33.2; 26.1; 40
SECONDARY
4 yr OS
56.4; 56.5; 38.2; 39.1; 53.3

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.

Eligibility Criteria

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
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00003816). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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